Kanzius - Enhanced systems and methods for RF-induced hyperthermia

United States Patent	7,510,555
Kanzius	March 31, 2009

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Enhanced systems and methods for RF-induced hyperthermia

Abstract

A method of inducing hyperthermia in at least a portion of a target area--e.g., a tumor or a portion of a tumor or targeted cancerous cells--is provided. Targeted RF absorption enhancers, e.g., antibodies bound to RF absorbing particles, are introduced into a patient. These targeted RF absorption enhancers will target certain cells in the target areas and enhance the effect of a hyperthermia generating RF signal directed toward the target area. The targeted RF absorption enhancers may, in a manner of speaking, add one or more RF absorption frequencies to cells in the target area, which will permit a hyperthermia generating RF signal at that frequency or frequencies to heat the targeted cells.

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Inventors:	Kanzius; John (Erie, PA)
Assignee:	Therm Med, LLC (Erie, PA)
Appl. No.:	11/050,422
Filed:	February 3, 2005

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Related U.S. Patent Documents

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	Application Number	Filing Date	Patent Number	Issue Date
	10969477	Oct., 2004
	60569348	May., 2004

What is claimed is:

1. A method for killing or damaging target cells in a patient, comprising: introducing into the patient RF absorption enhancers capable of selectively binding to the target cells and further capable of generating sufficient heat to kill or damage the bound target cells by heat generated solely by the application of an RF field generated by an RF signal between a transmission head and a reception head that is different from the transmission head; arranging the transmission and reception heads on opposite sides of a portion of the patient for treatment; and irradiating the portion of the patient between the transmission and reception heads containing RF absorption enhancers with an RF field to kill or damage the target cells from the heat generated by the RF absorption enhancers.

Source

Quantitative 3D Video Microscopy of HIV Transfer Across T Cell Virological Synapses

Science 27 March 2009:
Vol. 323. no. 5922, pp. 1743 - 1747
DOI: 10.1126/science.1167525

Reports

Wolfgang Hübner,¹ Gregory P. McNerney,³ Ping Chen,¹ Benjamin M. Dale,¹ Ronald E. Gordon,² Frank Y. S. Chuang,³ Xiao-Dong Li,⁴ David M. Asmuth,⁴ Thomas Huser,^3,4 Benjamin K. Chen^1*

The spread of HIV between immune cells is greatly enhanced by cell-cell adhesions called virological synapses, although the underlying mechanisms have been unclear. With use of an infectious, fluorescent clone of HIV, we tracked the movement of Gag in live CD4 T cells and captured the direct translocation of HIV across the virological synapse. Quantitative, high-speed three-dimensional (3D) video microscopy revealed the rapid formation of micrometer-sized "buttons" containing oligomerized viral Gag protein. Electron microscopy showed that these buttons were packed with budding viral crescents. Viral transfer events were observed to form virus-laden internal compartments within target cells. Continuous time-lapse monitoring showed preferential infection through synapses. Thus, HIV dissemination may be enhanced by virological synapse-mediated cell adhesion coupled to viral endocytosis.

¹ Division of Infectious Diseases, Department of Medicine, Immunology Institute, Mount Sinai School of Medicine, New York, NY 10029, USA.
² Department of Pathology, Mount Sinai School of Medicine, New York, NY 10029, USA.
³ NSF Center for Biophotonics Science and Technology, University of California Davis (UCD), Sacramento, CA 95817, USA.
⁴ Department of Internal Medicine, University of California Davis Medical Center, Sacramento, CA 95817, USA.

^* To whom correspondence should be addressed. E-mail: ben.chen@mssm.edu

Source

• An interesting informative presentation with numerous videos:
  

[SNIP]
It turns out that HIV doesn't work like this (mostly). In fact, it operates more much more sneakily -- like special forces -- viral ninjas, if you will. Instead of spreading out in the blood, HIV viruses transfer between infected cells through a structure called a virological synapse. (To be accurate, HIV does infect cells in a cell-free form -- this is discussed in the Introduction of the paper. However, cell-to-cell transfer of HIV is up to a thousand times more efficient and inhibiting it inhibits viral replication.)

http://scienceblogs.com/purepedantry/2009/03/watch_hiv_t-cell_transfer_live.php

Nanoparticles Open Door to Cancer Prevention

3/30/2009 7:04:59 AM

Perhaps the best way to fight cancer is to prevent it from developing in the first place, and based on newly published research from investigators at the University of Wisconsin-Madison, nanoparticles may be able to make cancer chemoprevention a reality. Using nanoparticles made of a biocompatible polymer, the investigators were able to encapsulate a molecule isolated from green tea that triggers apoptosis and inhibits angiogenesis, two key biochemical events that could prevent cancer. Hasan Mukhtar, Ph.D., led the team that published its results in the journal Cancer Research.

One of the chief issues in chemoprevention—the use of biologically active molecules to thwart cancer before it gains a foothold in the body—is that any such agents must be exceedingly safe, since it is likely that a person at risk for cancer would need to take the chemopreventive agent on a regular basis for a long time. Because of this requirement, many investigators have been screening naturally occuring molecules for chemopreventive activity. One such molecule, the green tea component epigallocatechin-3-gallate (EGCG), has demonstrated chemopreventive potential in a wide range of in vitro and in vivo studies. However, the body rapidly degrades this compound, limiting its clinical utility.

The Wisconsin team solved this problem using nanoparticles. When the investigators loaded biocompatible polymer nanoparticles with EGCG, they boosted its cancer-preventing activity by more than tenfold. Additional experiments confirmed that this increase resulted from a significantly longer half-life for EGCG in the body. This longer half-life correlated with a reduction in serum prostate-specific antigen levels in animals with implanted human prostate tumors.

This work, which is detailed in the paper “Introducing nanochemoprevention as a novel approach for cancer control: proof of principle with green tea polyphenol epigallocatechin-3-gallate,” was supported by the National Cancer Institute. Investigators from the Albany College of Pharmacy in New York also participated in this study. An abstract of this paper is available at the journal’s Web site.

View abstract.

Source

Zinc-Oxide Nanoparticles - Remarkable Breakthrough in Cancer Treatment

Boise State researchers have made a remarkable breakthrough in cancer treatment that may provide the "magic bullet" for the debilitating effects of chemotherapy.

The interdisciplinary group of researchers applied emerging nanotechnology techniques to traditional cancer research to come up with a highly effective method for the preferential killing of cancer cells while leaving ordinary cells healthy. This nanobiotechnology group is led by Boise State physics professor Alex Punnoose with strong contributions from biology professors Denise Wingett and Kevin Feris.

“One of the greatest challenges preventing advances in new therapeutic options for treating cancer is the inability of anticancer drugs to effectively differentiate between cancerous and normal healthy body cells,” said Wingett, a cancer researcher. “Many commonly used chemotherapeutic drugs target rapidly dividing cells but suffer from a relatively low therapeutic index, which is the ratio of toxic dose to effective dose.”

But the group discovered that zinc-oxide nanoparticles can preferentially kill cancer cells without impacting normal cells, a discovery that could potentially treat the cancer without the side effects caused by chemotherapy.

The group’s discovery is described in the paper “Preferential Killing of Cancer Cells and Activated Human T Cells Using ZnO Nanoparticles,” published in the July edition of the journal Nanotechnology. The paper has garnered significant attention in the scientific community, being downloaded more than 250 times in the first month of its publication, making it one of most popular articles in the 58 journals published by the Institute of Physics, the publisher of the journal Nanotechnology.

The article can be found at http://stacks.iop.org/0957-4484/19/295103.

“Until now, no group in the world has been able to produce inherent selective cancer-killing ability in nanoparticles,” Wingett said. “Current chemotherapy drugs typically consist of single molecules and do not provide much room for manipulation of the molecule. But nanoparticles can be modified so that certain characteristics, like cancer-killing attributes, can be accentuated. Because of this, we think there is room for improvement in what we have already demonstrated.”

Wingett said the selectivity of these nanomaterials may be enhanced by linking tumor-targeting proteins such as monoclonal antibodies, peptides, and small molecules to tumor-associated proteins, or by using nanoparticles for drug delivery. In addition to these future directions, the research team is exploring the possibility of altering the nanoparticles to further improve their inherent ability to kill cancer cells while sparing normal healthy body cells.

Cancer researchers across the country have taken notice of the work. Jame Abraham, the hematology/oncology section chief, director of the Comprehensive Breast Cancer Program and medical director at Mary Babb Randolph Cancer Center at West Virginia University, said that while more study is needed, the breakthrough has great promise.

“Oncology is always looking for a magic bullet, which can kill only the cancer cells, not killing the normal cells. This work is a major step toward that,” Abraham said. “I think this work will pave the way for more targeted therapies.”

The promise of the work has also helped the nanobiotech research group land a $503,000 National Science Foundation grant to acquire a fluorescent activated cell sorter that will give the research group greater ability to identify, analyze and sort nanoparticles.

In addition to enhancing this particular cancer research, the new equipment would support the research activity of at least 16 other Boise State researchers in the sciences, environmental health and engineering, as well as research being done at Northwest Nazarene University, the College of Idaho, the Boise Veterans Administration Medical Center, the Mountain States Tumor and Medical Research Institute and the local biotechnology industry.

Posted August 31st, 2008

Source

(WO/2009/039508) PREFERENTIAL KILLING OF CANCER CELLS AND ACTIVATED HUMAN T CELLS USING ZNO NANOPARTICLES

CLAIMS

What we claim is:

1. A method for preferentially killing cancer cells relative to normal cells by treating the cells with zinc oxide nanoparticles.

2. A method for preferentially killing activated T cells relative to unactivated T cells by treating the cells with zinc oxide nanoparticles.

3. A method for treating cancer by treating the patient with zinc oxide nanoparticles.

4. A method for treating autoimmune disease by treating the patient with zinc oxide nanoparticles.

Watching cells die

Published: 26 March 2009 10:15 AM

Source: The Engineer Online

The viscosity of different parts of cancer cells increases dramatically when they are blasted with light-activated cancer drugs, according to new images that provide fundamental insights into how cancer cells die.

The images, taken by researchers from Imperial College London, reveal the physical changes that occur inside cancer cells while they are dying as a result of Photodynamic Therapy (PDT). This cancer treatment uses light to activate a drug that creates a short-lived toxic type of oxygen, called singlet oxygen, which kills cancerous cells.

The research team behind the study says that revealing what happens to viscosity within a dying cancer cell is important because it helps give a better understanding of how cells function and which factors are important for controlling reactions inside cells. Ultimately, this could help scientists design more efficient drugs for Photodynamic Therapy and other treatments.

The research is also of wider significance because these are the first ever real-time maps showing viscosity changing over a period of time inside a cell during a biologically important process such as cell death.

Previous studies have shown that the viscosity of human cells and organs also changes in patients with diseases such as diabetes and atherosclerosis, said Dr Marina Kuimova from Imperial College London's Department of Chemistry, who carried out the research.

'We're still not quite sure exactly what the relationship is between increased stickiness inside cells and disease, but we expect that the two are related,' added Kuimova.

'Knowing more about these changes, and being able to map them when they occur in all kinds of different scenarios, from dying cancer cells, to diseased blood cells, could help us to better understand how some diseases and their treatments affect cell and organ function.'

Dr Kuimova and her colleagues were able to track viscosity as it changed inside live cancer cells thanks to a newly developed Photodynamic Therapy drug, with unusual fluorescent properties. The drug, which is made of a molecule with a spinning component like a rotor, emits different wavelengths of light depending on the viscosity of its surroundings.

The changing wavelengths of light emitted during experiments, and captured over a period of 10 minutes, showed that once the PDT drug was activated, the level of viscosity inside the cell increased dramatically. The researchers suggest that this increasing viscosity is caused by the toxic oxygen molecules released into the cell.

They think that increased levels of viscosity might even contribute directly to the cancer cell's further deterioration by slowing down vital communication and transport processes inside the cell.

Dr Stanley Botchway from the Science and Technology Facilities Council, which worked in collaboration with Imperial College London on the research, said: 'The huge viscosity we measured was surprising and it certainly gives a new insight into the change in cellular environment during cell death.'

However, the researchers noted that as viscosity in the cancerous cell increases, the toxic oxygen molecule's mission to kill the cell is slowed down too.

Dr Kuimova explained: 'It looks like while the increasing viscosity contributes to the cell's demise, these new "sticky" cell conditions can slow the drug down, so it’s not as straightforward a relationship as it might first appear.

'More work is needed to better understand the complex interplay between viscosity and cell death. We hope to use our imaging technique to track changes in viscosity in other kinds of cells as they occur in real time, to unlock some of the secrets of what goes on inside cells when they're functioning, malfunctioning or dying.'

The research was led by Imperial College London in collaboration with the Science and Technology Facilities Council's Rutherford Appleton Laboratory (RAL), Oxford University, King's College London, and the University of Aarhus in Denmark.

The work was funded by the Engineering and Physical Sciences Research Council, with support from the Science and Technology Facilities Council, and the Danish Foundation for Basic Research.

Source

The NANO

YouTube Video

Photodynamic therapy with meta-tetrahydroxyphenylchlorin

Photodynamic therapy with meta-tetrahydroxyphenylchlorin (Foscan®) in the management of squamous cell carcinoma of the head and neck: experience with 35 patients

Kai Johannes Lorenz¹ and Heinz Maier¹

(1)	Department of Otolaryngology/Head and Neck Surgery, German Armed Forces Hospital of Ulm, Oberer Eselsberg 40, 89081 Ulm, Germany

Received: 27 October 2008 Accepted: 26 February 2009 Published online: 17 March 2009

Abstract Photodynamic therapy (PDT) is a relatively new method of treating superficial tumours of the skin and mucosa. After the injection of a photosensitising agent, the tumour area is exposed to non-thermal laser light. This causes a phototoxic reaction, producing oxygen radicals that destroy tumour cells. From November 2003 to July 2007, a total of 35 patients with recurrent squamous cell carcinoma or secondary tumours of the head and neck region were treated with PDT at the German Armed Forces Hospital in Ulm. These patients had failed or found unsuitable for other treatments. Meta-tetrahydroxyphenylchlorin (mTHPC), known under the trade name of Foscan^®, was used as the photosensitising agent. Local control was achieved in 21 patients (60%) and partial remission in 10 patients (28.5%). Four patients (11.5%) did not respond to PDT treatment. The mean duration of overall survival was 401.45 (±321.2) days, median was 356 after the completion of treatment. The mean duration of recurrence-free survival was 327.7 (±131.1) days, median was 181 for patients with complete remission. None of the patient developed serious complications. Photodynamic therapy is an important treatment option for patients who present with recurrent carcinoma or secondary tumours of the upper aerodigestive tract and who have failed or unsuitable for other treatments. Due to the excellent treatment results that have been achieved so far, PDT may in the future also play a role in the primary treatment of superficial tumours of the oral cavity, pharynx and larynx.

Keywords Photodynamic therapy - Foscan - mTHPC - Head and neck tumours - Squamous cell carcinoma

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Kai Johannes Lorenz Email: kai.lorenz@extern.uni-ulm.de

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Hollow gold nanospheres show promise for biomedical and other applications

Public release date: 22-Mar-2009

Contact: Tim Stephens
stephens@ucsc.edu
831-459-2495
University of California - Santa Cruz

SALT LAKE CITY, UT--A new metal nanostructure developed by researchers at the University of California, Santa Cruz, has already shown promise in cancer therapy studies and could be used for chemical and biological sensors and other applications as well.

The hollow gold nanospheres developed in the laboratory of Jin Zhang, a professor of chemistry and biochemistry at UCSC, have a unique set of properties, including strong, narrow, and tunable absorption of light. Zhang is collaborating with researchers at the University of Texas M. D. Anderson Cancer Center, who have used the new nanostructures to target tumors for photothermal cancer therapy. They reported good results from preclinical studies earlier this year (Clinical Cancer Research, February 1, 2009).

Zhang will describe his lab's work on the hollow gold nanospheres in a talk on Sunday, March 22, at the annual meeting of the American Chemical Society in Salt Lake City.

"What makes this structure special is the combination of the spherical shape, the small size, and the strong absorption in visible and near infrared light," Zhang said. "The absorption is not only strong, it is also narrow and tunable. All of these properties are important for cancer treatment."

Zhang's lab is able to control the synthesis of the hollow gold nanospheres to produce particles with consistent size and optical properties. The hollow particles can be made in sizes ranging from 20 to 70 nanometers in diameter, which is an ideal range for biological applications that require particles to be incorporated into living cells. The optical properties can be tuned by varying the particle size and wall thickness.

In the cancer studies, led by Chun Li of the M. D. Anderson Cancer Center, researchers attached a short peptide to the nanospheres that enabled the particles to bind to tumor cells. After injecting the nanospheres into mice with melanoma, the researchers irradiated the animals' tumors with near-infrared light from a laser, heating the gold nanospheres and selectively killing the cancer cells to which the particles were bound.

Cancer therapy was not the goal, however, when Zhang's lab began working several years ago on the synthesis and characterization of hollow gold nanospheres. Zhang has studied a wide range of metal nanostructures to optimize their properties for surface-enhanced Raman scattering (SERS). SERS is a powerful optical technique that can be used for sensitive detection of biological molecules and other applications.

Adam Schwartzberg, then a graduate student in Zhang's lab at UCSC, initially set out to reproduce work reported by Chinese researchers in 2005. In the process, he perfected the synthesis of the hollow gold nanospheres, then demonstrated and characterized their SERS activity.

"This process is able to produce SERS-active nanoparticles that are significantly smaller than traditional nanoparticle structures used for SERS, providing a sensor element that can be more easily incorporated into cells for localized intracellular measurements," Schwartzberg, now at UC Berkeley, reported in a 2006 paper published in Analytical Chemistry.

The collaboration with Li began when Zhang heard him speak at a conference about using solid nanoparticles for photothermal cancer therapy. Zhang immediately saw the advantages of the hollow gold nanospheres for this technique. Li uses near-infrared light in the procedure because it provides good tissue penetration. But the solid gold nanoparticles he was using do not absorb near-infrared light efficiently. Zhang told Li he could synthesize hollow gold nanospheres that absorb light most efficiently at precisely the wavelength (800 nanometers) emitted by Li's near-infrared laser.

"The heat that kills the cancer cells depends on light absorption by the metal nanoparticles, so more efficient absorption of the light is better," Zhang said. "The hollow gold nanospheres were 50 times more effective than solid gold nanoparticles for light absorption in the near-infrared."

Zhang's group has been exploring other nanostructures that can be synthesized using the same techniques. For example, graduate student Tammy Olson has designed hollow double-nanoshell structures of gold and silver, which show enhanced SERS activities compared to the hollow gold nanospheres.

The ability to tune the optical properties of the hollow nanospheres makes them highly versatile, Zhang said. "It is a unique structure that offers true advantages over other nanostructures, so it has a lot of potential," he said.

Source

Monoclonal antibodies primed to become potent immune weapons against cancer

March 20th, 2009

New research suggests that monoclonal antibody therapy of cancer can be improved to be much more powerful than it is today, says a researcher at Georgetown University Medical Center's Lombardi Comprehensive Cancer Center in the March 21 issue of the Lancet.

"We believe that antibody therapy has the capacity to immunize people against cancer," says Louis Weiner, MD, director of the cancer center at GUMC and an internationally recognized expert in development and use of monoclonal antibodies. "Treatment modifications might be able to prolong, amplify, and shape a continuous immune response to cancer cells."

Weiner was asked by Lancet editors to write a review article discussing the newest research in this field. His co-authors are Madhav Dhodapkar, MD, of Yale University and Soldano Ferrone, MD, of the University of Pittsburgh.

Their analysis, based on reviewing the last eight years of research on monoclonal antibody treatment, suggests that a new era in use of these therapies is just around the corner. "Scientists have been able to use new tools to measure effectiveness of these therapies, and have found that antibodies are capable of stimulating the immune system in ways that had not been appreciated to date, and which we can now take advantage of," Weiner says.

Antibodies are immune system proteins that seek out and neutralize molecules they recognize as foreign to a body, such as viruses and bacteria. Monoclonal antibodies are proteins crafted in a laboratory to recognize specific receptors, or antigens, on cancer cells; some antigens promote uncontrolled growth. These antibodies are designed to both attach to cancer receptors to inhibit their function and to alert and activate the immune system to the presence of these receptor proteins.

Monoclonal antibodies already offer effective treatment for a wide range of cancers, including breast cancer (Herceptin®, Avastin®), colorectal cancer (Erbitux®, Avastin), lung cancer (Avastin), and blood cancers (Rituxan®, Campath®), but they have appeared to primarily work by forcing tumor related receptors to shut down pro-growth signals, Weiner says.

"For years it has been presumed that the ability of antibodies to interfere with malignant cell-related signaling is the dominant mechanism of anticancer activity, but we have also known that the normal job of an antibody is to deliver an antigen to the body's immune system which then destroys the target," Weiner says.

Recent research by Weiner and others, however, now shows that antibodies can inhibit function not only as signaling manipulators but also as initiators of immune responses that leads to control of cancer, the authors say.

"We believe that Herceptin and Rituxan, as examples, work in part by immunizing people against cancer, but at this point, the magnitude of that response is variable and is frequently very small," Weiner says.

Scientists now believe that it will be possible to alter the antibodies so that they induce both kinds of human immunity - the innate immune response that is short-lasting and which directly kills tumor cells, and a long-lasting "memory" response that comes from the adaptive immune response. "We have long thought that monoclonal antibodies are capable of stimulating the innate immune system, but we now have evidence that the therapy can prime an adaptive response as well. Such responses would make the treatment much more powerful, capable of keeping cancer under control," he says.

"For the first time we are using technology that can measure the immune response that is occurring in monoclonal antibody treatment, and which will help us build better antibodies that amplify and shape that immune response to become more powerful," Weiner says.

And in the future, it may be possible to build antibodies that are targeted to existing targets on a patient's tumor, as well as to targets that may appear as the cancer mutates. "This one-two punch would anticipate how the tumor changes over time and cut off the cancer's escape route," Weiner says. "These new directions are very exciting."

Source: Georgetown University Medical Center

Source

Photoelectrochemical efficiency of titania photoanodes enhanced

Mar 5, 2009

Hydrogen production from sunlight by splitting water using photoelectrochemical electrolysis is the most direct method for solar-to-hydrogen conversion. Looking at the process in more detail, nanotubular titania (TiO₂) emerges as one of the most promising photo-anode materials for water splitting using solar radiation thanks to the combination of a band structure that straddles the reduction and oxidation potential of water, a high corrosion resistance in aqueous electrolytes and the material's low cost.

Photocurrent density of nanotubular titania

So far, so good. However, the large bandgap of TiO₂ (3.0–3.2 eV) allows photoconversion of only UV radiation, which comprises less than 7% of the solar energy spectrum. Thus, bandgap reduction of TiO₂ is a key requirement for effective solar-to-hydrogen conversion.

In a recent study published in Nanotechnology, researchers at the University of Arkansas at Little Rock and the University of Nevada, Reno, developed a process based on nanostructure synthesis and plasma surface modification to enhance the photoelectrochemical conversion efficiency of titania photoanodes.

Titania photoanodes with nanotubular structures were synthesized by electrochemical anodization of titanium thin foils. The photoanode surfaces were then subjected to low-pressure nitrogen plasma. It was found that the plasma treatment significantly enhanced the photoelectrochemical activity of the samples; the photocurrent density of plasma treated material was approximately 80% higher than that of the control electrodes.

The plasma treatment removed surface contaminants, minimized the charge carrier traps and provided n-type doping of the photonaode surface with nitrogen. The increase in photoactivity was ascribed to the surface modifications by plasma treatment and increased absorption of visible light due to nitrogen doping of the photoanode surface, narrowing the bandgap. XPS analysis confirmed doping of nitrogen in the TiO₂ surface. Plasma treatments also increased surface roughness and wettabilty, resulting in a higher electrode/electrolyte interfacial contact area for enhancing electrolysis.

While plasma surface doping does not hinder an efficient transport of charge carrier through the bulk material, further advancement of the method is needed to provide effective n-doping over the depth of the depletion layer for efficient light absorption and charge separation.

Based on its results, the group believes that a synergistic combination of nanostructure synthesis of photoanodes and surface structure and chemical modification may advance photoelectrochemical generation of hydrogen using photostable semiconducting electrodes.

About the author

This work was performed at the University of Arkansas at Little Rock and University of Nevada, Reno, and was supported by the United States Department of Energy and Arkansas Science and Technology Authority. Dr Rajesh Sharma is a Research Faculty at the Graduate Institute of Technology at the University of Arkansas at Little Rock. Prajna P Das and Vishal Mahajan are graduate students at the University of Nevada, Reno. Dr Mano Misra is professor at the Department of Chemical and Metallurgical Engineering at the University of Nevada, Reno. Jacob Bock is an undergraduate student at the University of Arkansas at Little Rock. Dr Steve Trigwell is manager of the Applied Science and Technology Laboratories at ASRC Aerospace, in the Kennedy Space Center, Florida. Dr Alexandru Biris and Dr Malay Mazumder are assistant professor and Emeritus professor respectively at the Applied Science Department at the University of Arkansas at Little Rock.

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Nano Team Increases Efficiency of Sun-to-Fuel Process

Libraries Science News		Keywords NANOTECHNOLOGY, FUEL CELLS SOLAR CONVERSION
Contact Information Available for logged-in reporters only
Description Researchers find great promise in a process that could use solar energy to use hydrogen, the third most abundant element on earth's surface, as the ultimate alternative to fossil fuels. This process increase dramatically the efficiency of titania photoanodes used to convert solar energy into hydrogen in fuel cells.

Newswise — Researchers at UALR -- the University of Arkansas at Little Rock -- said they have developed a process involving nanostructure that shows great promise in boosting the efficiency of titania photoanodes used to convert solar energy into hydrogen in fuel cells.

Hydrogen, the third most abundant element on earth’s surface, has long been recognized as the ultimate alternative to fossil fuels as an energy carrier. Automobiles using hydrogen directly or in fuel cells have already been developed, but the biggest challenge has been how to produce hydrogen using renewable sources of energy.

Scientists in Japan discovered in 1970 that semiconductor oxide photoanodes can harness the photons from solar radiation and used them to split a water molecule into hydrogen and oxygen, but process was too inefficient to be viable.

The UALR team, working with researchers at the University of Nevada, Reno, and supported by the U.S. Department of Energy and the Arkansas Science and Technology Authority (ASTA), has reported an 80 percent increase in efficiency with a new process.

The new process has been outlined in a recent study published in the journal Nanotechnology and also reported on the website Nanotechweb.org.

Electrochemical methods were utilized to synthesize titania photoanodes with nanotubular structures. The photoanode surfaces were then subjected to low-pressure nitrogen plasma to modify their surface properties. The plasma treatment increased the light absorption by the photoanode surface. It also removed surface impurities that are detrimental for photoelectrochemical hydrogen production.

“The plasma treatment significantly enhanced the photo electrochemical activity of the samples,” said Dr. Rajesh Sharma, assistant research professor in applied science in UALR’s Donaghey College of Engineering and Information Technology (EIT). “The photocurrent density of plasma treated material was approximately 80 percent higher than that of the control electrodes.”

Sharma’s highly interdisciplinary research interests encompass materials science, electrostatics, and particulate technology. He developed an atmospheric pressure plasma reactor for surface modification of materials in a variety of applications.

In addition to his work on nanostructured materials for photoelectrochemical processes, he is also working on development of an electrodynamic screen for dust mitigation application for future Mars and Lunar missions.

In addition to Sharma, the project team includes Drs. Alexandru Biris, assistant professor in applied science and chief science officer of Nanotechnology Center at UALR; UALR Professor-emeritus Malay Mazumder, and UALR undergraduate student Jacob Bock of Cabot.

Team members in Nevada include Dr. Mano Misra in the Department of Chemical and Metallurgical Engineering at UNR, and graduate students Prajna P. Das and Vishal Mahajan at the UNR.

Dr. Steve Trigwell, manager of the Applied Science and Technology Laboratories at the Kennedy Space Center in Florida, also participated in the research.

Source

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Now - as to Applied Nanotech (APNT) - is Yaniv et al's TiO2 work relevant?:

United States Patent 7,300,634
Yaniv , et al. November 27, 2007
http://patft.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PALL&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.htm&r=1&f=G&l=50&s1=7,300,634.PN.&OS=PN/7,300,634&RS=PN/7,300,634

PhotoScrub®
http://www.appliednanotech.net/TechnologyPlatforms/materials/PhotoScrub-R.asp

• I envisage an energy source like that proposed above creating H2 from H2O using titanium oxide WITH APNT's ASSISTANCE AND INVOLVEMENT. Perhaps I am expecting too much...but I'd still like to see it. It's pretty important and would make all our hopes and desires come to fruition. We helped replace oil with something better, cheaper and from Texas, too. ;-)

Nanotechnology may offer alternative to radiation for cancer patients

Last Updated: Wednesday, March 18, 2009 | 5:35 PM ET

CBC News

Nanotechnology, the science of the really small, is already applied in hundreds of consumer products to enhance colour and durability of paints or make socks less smelly, but it's real promise may lie in medicine.

Scientists can use nanoparticles created in a laboratory that are tens of thousands of times smaller than the width of a strand of hair to deliver drugs deep into the body, penetrating membranes in ways no pill has been able to do.

A nanoparticle can be attached to antibodies or chemicals that recognize tumour cells and can target and kill cancer cells but spare surrounding tissue.

Jie Chen, a nanotechnology engineer at the University of Alberta, is using nanotechnology to develop new cancer treatments that could one day replace radiation and chemotherapy. He is doing experiments with injected nanoparticles that contain a bamboo compound that is sensitive to ultrasound.

"So when the ultrasound is used and treated or targetted towards these compounds, then you will activate and generate something which can destroy the cancer so it's much safer compared to conventional radiation."

Dr. Nils Petersen, director general of the National Institute for Nanotechnology in Edmonton said nanotech promises better, faster and cheaper ways of diagnosing and treating disease, developing drugs — even regrowing teeth.

.......

The researchers in Edmonton are starting to organize a human trial of the ultrasound cancer treatment, saying they are eager to put nanotechnology to work in medicine.

Source

Nanoparticle self-lighting photodynamic therapy for deep cancer treatment

Author: 佚名
UpdateTime: 2008-9-21 20:18:33 Hits: 231 Keyword: photodynamic, cancer treatment

Posted February 13 2008

(Nanowerk Spotlight) Photodynamic therapy (PDT) is a cancer treatment that combines a chemical compound, called a photosensitizer, with a particular type of light to kill cancer cells. The treatment works like this: the photosensitizing agent is injected into the bloodstream. The agent is absorbed by cells all over the body, but stays in cancer cells longer than it does in normal cells. One to three days after injection, when most of the agent has left normal cells but remains in cancer cells, the tumor is exposed to light. The photosensitizer in the tumor absorbs the light and produces an active form of oxygen (singlet oxygen) that destroys nearby cancer cells. PDT has been used for the past 30 years and is a treatment that works. PDT takes very little time, is often done as an outpatient, can be accurately targeted to the affected area, can be repeated, and has no long-term side effects. It also isn't as expensive or invasive as some other cancer treatment options. The limitation of this form of cancer treatment is that the light needed to activate most photosensitizers cannot pass through more than one centimeter of tissue. For this reason, PDT is usually used to treat tumors on or just under the skin or on the lining of internal organs or cavities. PDT is also less effective in treating large or deep tumors, because the light cannot pass far into these tumors. Researchers have now proposed a new PDT system in which the light is generated by x-ray scintillation nanoparticles with attached photosensitizers. When the nanoparticle-photosensitizer conjugates are targeted to tumors and stimulated by x-rays during radiotherapy, the particles generate visible light that can activate the photosensitizers for photodynamic therapy. Therefore, the radiation and photodynamic therapies are combined and occur simultaneously, and the tumor destruction can be more efficient. More importantly, it can be used for deep tumor treatment as x-rays can penetrate through tissue.

"I have been working on nanotechnologies for 15 years" Dr. Wei Chen tells Nanowerk. "My original work was trying to use quantum dots for in vivo imaging. I was facing the challenge of light penetration. I also have experience with the design and synthesis scintillation nanoparticles. I knew light delivery was also a challenging issue for PDT, just like in vivo optical imaging. Then, I came up with the idea to combine photodynamic therapy with radiation therapy through scintillation nanoparticles for deep cancer treatment."

Chen, an assistant professor of Nano-Bio Physics at the University of Texas at Arlington, points out that photodynamic therapy is not new, and radiation therapy is not new; but the combination of both through scintillation nanoparticles is new and potentially important for deep cancer treatment. He introduced the concept in a paper in the Journal of Nanoscience and Nanotechnology in April 2006 ("Using Nanoparticles to Enable Simultaneous Radiation and Photodynamic Therapies for Cancer Treatment").

Although PDT has been widely used for skin cancer treatment, its application for deep cancer treatment is still a challenging issue because the light for PDT activation cannot penetrate deep into the tissue. To solve this problem, Chen and his collaborators propose a new PDT system in which the light is generated by scintillation luminescence nanoparticles (such as X-ray luminescence nanoparticles) with the attached photosensitizers.

Chen explains that, when the nanoparticle-photosensitizer conjugates are targeted to a tumor and stimulated by X-ray or other radiation sources during radiation therapy, the particles will generate light (energy) to activate the photosensitizers. With this novel therapeutic approach, no external light is necessary to activate the photosensitizing agent within tumors. Tissue thickness therefore would no longer be a limiting issue for PDT.

"Effectively, the radiation and photodynamic therapies are combined and occur simultaneously, and the tumor destruction will be more effective" he says. "More importantly, it can be used for deep tumor treatment as X-ray can penetrate deep into the tissue. No external light is necessary to deliver to the tumor and only an extremely low dose of radiation is needed for the treatment. Therefore, this provides a simple but more efficient modality for cancer treatment. We called this new modality Nanoparticle Self-Lighting Photodynamic Therapy."

Working with Chen's group are Dr. Shaopeng Wang and Dr. Yuanfang Liu, senior research scientists at ICx/Nomadics Inc.; Dr. Alan G. Joly, an optical physicist and a senior scientist at Pacific Northwest National Laboratory; and Dr. Carey Pope, Regents Professor And Head Sitlington Chair In Toxicology at the Center for Veterinary Health Sciences, Oklahoma State University.

The researchers reported their findings in a recent paper published in the January 29, 2008 online edition of Applied Physics Letters ("Investigation of water-soluble x-ray luminescence nanoparticles for photodynamic activation").

Their pilot studies indicate that water-soluble scintillation nanoparticles (the particle size in the study was about 15 nm) can potentially be used to activate photodynamic therapy as a promising deep cancer treatment modality.

For practical applications, the nanoparticle-porphyrin conjugates must be delivered to the tumor cells in vehicles such as antibodies, peptides, liposomes or other functional molecules. In designing the delivery vehicles one needs to consider how they will affect the quantum yield of singlet oxygen. Chen and his team used folic acid to target folate receptors at tumor cells. Their results indicate that folic acid has no effect on the quantum yield of singlet oxygen production in the nanoparticle conjugates, making this system practical for photodynamic activation applications.

Initial results of the studies have been promising. But before Nanoparticle Self-Lighting Photodynamic Therapy becomes a clinical reality, the researchers must overcome two main challenges: 1) they need to develop a class of water-soluble scintillation nanoparticles with very high quantum efficiencies of X-ray luminescence, and 2) they need to improve the targeting capabilities of the nanoparticle- photosensitizer compound – but this is a challenge for all drug-based cancer treatments.

By Michael Berger. Copyright 2008 Nanowerk LLC

Source

Waking up dormant HIV

March 16th, 2009

HAART (highly active anti-retroviral therapy) has emerged as an extremely effective HIV treatment that keeps virus levels almost undetectable; however, HAART can never truly eradicate the virus as some HIV always remains dormant in cells. But, a chemical called suberoylanilide hydroxamic acid (SAHA), recently approved as a leukemia drug, has now been shown to 'turn on' latent HIV, making it an attractive candidate to weed out the hidden virus that HAART misses.

Matija Peterlin at UCSF and colleagues had previously identified another chemical called HMBA that could activate latent HIV, but the risk of several toxic side effects made HMBA clinically non-viable. However, the chemically similar SAHA had received FDA approval, making it a potentially safer alternate.

So, the researchers examined whether SAHA had any effect on HIV latency. They found that SAHA could indeed stimulate latent HIV to begin replicating, which exposes the infected cell to HAART drugs. SAHA could activate HIV in both laboratory cells as well as from blood samples taken from HIV patients on antiretroviral therapy. Importantly, this successful activation was achieved using clinical doses of SAHA, suggesting toxicity will not be a problem.

More information: This study appeared in the March 13 issue of Journal of Biological Chemistry, "Suberoylanilide hydroxamic acid reactivates HIV from latently infected cells" by Xavier Contreras, Marc Schwenker, Chin-Shih Chen, Joseph M. McCune, Steven G. Deeks, Jeffrey Martin, and B. Matija Peterlin

Article link: http://www.jbc.org/cgi/content/full/284/11/6782

Source: American Society for Biochemistry and Molecular Biology

http://www.physorg.com/news156424517.html

Suberoylanilide Hydroxamic Acid Reactivates HIV from Latently Infected Cells^*

Originally published In Press as doi:10.1074/jbc.M807898200 on January 9, 2009 J. Biol. Chem., Vol. 284, Issue 11, 6782-6789, March 13, 2009

Xavier Contreras¹, Marc Schweneker², Ching-Shih Chen^¶, Joseph M. McCune³, Steven G. Deeks^||, Jeffrey Martin^**, and B. Matija Peterlin⁴

From the Department of Medicine, University of California, San Francisco, California 94143, Division of Experimental Medicine, ^||HIV/AIDS Division, and ^**Department of Epidemiology and Biostatistics, San Francisco General Hospital, University of California, San Francisco, California 94143, and ^¶Division of Medicinal Chemistry, College of Pharmacy, The Ohio State University, Columbus, Ohio 43210

Human immunodeficiency virus (HIV) persists in a latent form in infected individuals treated effectively with highly active antiretroviral therapy (HAART). In part, these latent proviruses account for the rebound in viral replication observed after treatment interruption. A major therapeutic challenge is to purge this reservoir. In this study, we demonstrate that suberoylanilide hydroxamic acid (SAHA) reactivates HIV from latency in chronically infected cell lines and primary cells. Indeed, P-TEFb, a critical transcription cofactor for HIV, is released and then recruited to the viral promoter upon stimulation with SAHA. The phosphatidylinositol 3-kinase/Akt pathway is involved in the initiation of these events. Using flow cytometry-based single cell analysis of protein phosphorylation, we demonstrate that SAHA activates this pathway in several subpopulations of T cells, including memory T cells that are the major viral reservoir in peripheral blood. Importantly, SAHA activates HIV replication in peripheral blood mononuclear cells from individuals treated effectively with HAART. Thus SAHA, which is a Food and Drug Administration-approved drug, might be considered to accelerate the decay of the latent reservoir in HAART-treated infected humans.

---

Received for publication, October 15, 2008 , and in revised form, January 9, 2009.

^* This work was supported, in whole or in part, by National Institutes of Health Grants AI49104 and AI058708 (to B. M. P.) and R01 AI40312 and AI47062 (to J. M. M.). This work was also supported by the University of California, San Francisco, Center for AIDS Research Grants P30 AI027763, P30 MH59037, and CC99-SF-001 and the University of California, San Francisco, Clinical and Translational Research Institute Grant UL1 RR024131, a component of the National Institutes of Health Roadmap for Medical Research. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement"in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ Supported by a grant from the California Foundation for AIDS Research.

² Supported by the University-wide AIDS Research Program Grant F05-GI-219.

³ Recipient of National Institutes of Health Grant DPI OD00329 (Director's Pioneer Award Program, part of the National Institutes of Health Roadmap for Medical Research) and the Burroughs Wellcome Fund Clinical Scientist Award in Translational Research.

⁴ To whom correspondence should be addressed: University of California, San Francisco, 533 Parnassus Ave., Rm. U432, Box 0703, San Francisco, CA 94143. Fax: 415-502-1901; E-mail: matija.peterlin@ucsf.edu.

http://www.jbc.org/cgi/content/abstract/284/11/6782

Nanocapacitors with Big-Energy Storage

Monday, March 16, 2009

Nanocapacitors with Big-Energy Storage

Nanopore arrays combine high power and storage capacity.

By Katherine Bourzac


Nanopore power: Arrays of capacitors built inside nanopores are shown here in a scanning electron micrograph image overlaid with an illustration that shows their design. The pores are etched into an aluminum substrate (dark yellow). The capacitors form two thin layers of metal (blue) separated by a layer of insulating material (light yellow).
Credit: A. James Clark School of Engineering, University of Maryland

The ultimate electronic energy-storage device would store plenty of energy but also charge up rapidly and provide powerful bursts when needed. Sadly, today's devices can only do one or the other: capacitors provide high power, while batteries offer high storage.

Now researchers at the University of Maryland have developed a kind of capacitor that brings these qualities together. The research is in its early stages, and the device will have to be scaled up to be practical, but initial results show that it can store 100 times more energy than previous devices of its kind. Ultimately, such devices could store surges of energy from renewable sources, like wind, and feed that energy to the electrical grid when needed. They could also power electric cars that recharge in the amount of time that it takes to fill a gas tank, instead of the six to eight hours that it takes them to recharge today.

There are many different kinds of batteries and capacitors, but in general, batteries can store large amounts of energy yet tend to charge up slowly and wear out quickly. Capacitors, meanwhile, have longer lifetimes and can rapidly discharge, but they store far less total energy. Electrochemists and engineers have been working to solve this energy-storage problem by boosting batteries' power and increasing capacitors' storage capacity.

Sang Bok Lee, a chemistry professor, and Gary Rubloff, a professor of engineering and director of the Maryland NanoCenter, created nanostructured arrays of electrostatic capacitors. Electrostatic capacitors are the simplest kind of electronic-energy-storage device, says Rubloff. They store electrical charge on the surface of two metal electrodes separated by an insulating material; their storage capacity is directly proportional to the surface area of these sandwich-like electrodes. The Maryland researchers boosted the storage capacity of their capacitors by using nanofabrication to increase their total surface area. Their electrodes work in the same way as ones found in conventional capacitors, but instead of being flat, they are tubular and tucked deep inside nanopores.

The fabrication process begins with a glass plate coated with aluminum. Pores are etched into the plate by treating it with acid and applying a voltage. It's possible to make very regular arrays of tiny but deep pores, each as small as 50 nanometers in diameter and up to 30 micrometers deep, by carefully controlling the reaction conditions. The process is similar to one used to make memory chips. "Next you deposit a very thin layer of metal, then a thin layer of insulator, then another thin layer of metal into these pores," says Rubloff. These three layers act as the nanocapacitors' electrodes and insulating layer. A layer of aluminum sits on top of the device and serves as one electrical contact; the other contact is made with an underlying aluminum layer.

This "fractal-like structure greatly increases the surface area," says Joel Schindall, associate director of MIT's Laboratory for Electromagnetic and Electronic Systems, who was not involved in the work.

In a paper published online this week in the journal Nature Nanotechnology, the Maryland group describes making 125-micrometer-wide arrays, each containing one million nanocapacitors. The surface area of each array is 250 times greater than that of a conventional capacitor of comparable size. The arrays' storage capacity is about 100 microfarads per square centimeter.

But surface area isn't the only determinant of energy density. The Maryland group's nanocapacitors also benefit from the very small spacing between their electrodes, and the work is unique in this respect, says Robert Hebner, director of the Center for Electromechanics at the University of Texas at Austin. Hebner was not involved in the Maryland research.

If the electrodes are far apart, the like charges on their surfaces strongly repel each other. When the electrodes are placed closer together, the negative and positive charges on either side balance out these repulsive forces, and more total charge can be stored in a given area. The total thickness of each nanocapacitor is just 25 nanometers, and the charges can pack very close together. "It's impressive," says Hebner. "I hope they can scale it up."

So far, the nanocapacitor arrays can't store much total energy because they're so small. "Instead of making these little dots, we want to make a large area that contains billions of nanocapacitors to store large amounts of energy," says Lee. Both he and Rubloff say that scaling up to a practical level is not trivial, but the pair is working together to make larger arrays. "There are many scale-up issues," says Rubloff. "We'll look at how large we can make these and still have all of them work."

Even if this problem is solved, they'll still have to make sure that they can effectively connect multiple arrays to one another. But Hebner says that this problem is not intractable, and he points to devices on the market, including sensitive magnetic detectors, that successfully overcome similar connectivity issues.

One advantage of the new fabrication method is that the nanopore dimensions and the respective thicknesses of the electrode and insulator can be carefully controlled. "Regularity and uniformity are central to scaling nanotechnologies up to something manufacturable and commercializable," says Rubloff. "There are still major hurdles, but we're trying to decide how to commercialize this--there's definitely a thirst to do so."

Source

Letter Abstract

Nature Nanotechnology

Published online: 15 March 2009 | doi:10.1038/nnano.2009.37

Nanotubular metal–insulator–metal capacitor arrays for energy storage

Parag Banerjee^1,2, Israel Perez^1,2, Laurent Henn-Lecordier^1,2, Sang Bok Lee^3,4 & Gary W. Rubloff^1,2,5

Nanostructured devices have the potential to serve as the basis for next-generation energy systems that make use of densely packed interfaces and thin films¹. One approach to making such devices is to build multilayer structures of large area inside the open volume of a nanostructured template. Here, we report the use of atomic layer deposition to fabricate arrays of metal–insulator–metal nanocapacitors in anodic aluminium oxide nanopores. These highly regular arrays have a capacitance per unit planar area of 10 F cm^-2 for 1-m-thick anodic aluminium oxide and 100 F cm^-2 for 10-m-thick anodic aluminium oxide, significantly exceeding previously reported values for metal–insulator–metal capacitors in porous templates^{2, 3, 4, 5, 6}. It should be possible to scale devices fabricated with this approach to make viable energy storage systems that provide both high energy density and high power density.

1. Department of Materials Science and Engineering, University of Maryland, College Park, Maryland 20742, USA
2. Institute for Systems Research, University of Maryland, College Park, Maryland 20742, USA
3. Department of Chemistry and Biochemistry, University of Maryland, College Park, Maryland 20742, USA
4. Department of Nanoscience and Technology, Korea Advanced Institute of Science and Technology, 335 Gwahangno, Yuseong-gu, Daejeon 305-701, Korea
5. Institute for Research in Electronics and Applied Physics, University of Maryland, College Park, Maryland 20742, USA

Correspondence to: Sang Bok Lee^3,4 e-mail: slee@umd.edu

Correspondence to: Gary W. Rubloff^1,2,5 e-mail: rubloff@umd.edu

Source

Re-engineered battery material could lead to rapid recharging of many devices/MIT/Ceder, Kang

3/13/2009 6:17:53 PM
Re-engineered battery material could lead to rapid recharging of many devices

MIT engineers have created a kind of beltway that allows for the rapid transit of electrical energy through a well-known battery material, an advance that could usher in smaller, lighter batteries -- for cell phones and other devices -- that could recharge in seconds rather than hours.

The work could also allow for the quick recharging of batteries in electric cars, although that particular application would be limited by the amount of power available to a homeowner through the electric grid.

The work, led by Gerbrand Ceder, the Richard P. Simmons Professor of Materials Science and Engineering, is reported in the March 12 issue of Nature. Because the material involved is not new -- the researchers have simply changed the way they make it -- Ceder believes the work could make it into the marketplace within two to three years.

State-of-the-art lithium rechargeable batteries have very high energy densities -- they are good at storing large amounts of charge. The tradeoff is that they have relatively slow power rates -- they are sluggish at gaining and discharging that energy. Consider current batteries for electric cars. "They have a lot of energy, so you can drive at 55 mph for a long time, but the power is low. You can't accelerate quickly," Ceder said.

Why the slow power rates? Traditionally, scientists have thought that the lithium ions responsible, along with electrons, for carrying charge across the battery simply move too slowly through the material.

About five years ago, however, Ceder and colleagues made a surprising discovery. Computer calculations of a well-known battery material, lithium iron phosphate, predicted that the material's lithium ions should actually be moving extremely quickly.

"If transport of the lithium ions was so fast, something else had to be the problem," Ceder said.

Further calculations showed that lithium ions can indeed move very quickly into the material but only through tunnels accessed from the surface. If a lithium ion at the surface is directly in front of a tunnel entrance, there's no problem: it proceeds efficiently into the tunnel. But if the ion isn't directly in front, it is prevented from reaching the tunnel entrance because it cannot move to access that entrance.

Ceder and Byoungwoo Kang, a graduate student in materials science and engineering, devised a way around the problem by creating a new surface structure that does allow the lithium ions to move quickly around the outside of the material, much like a beltway around a city. When an ion traveling along this beltway reaches a tunnel, it is instantly diverted into it. Kang is a coauthor of the Nature paper.

Using their new processing technique, the two went on to make a small battery that could be fully charged or discharged in 10 to 20 seconds (it takes six minutes to fully charge or discharge a cell made from the unprocessed material).

Ceder notes that further tests showed that unlike other battery materials, the new material does not degrade as much when repeatedly charged and recharged. This could lead to smaller, lighter batteries, because less material is needed for the same result.

"The ability to charge and discharge batteries in a matter of seconds rather than hours may open up new technological applications and induce lifestyle changes," Ceder and Kang conclude in their Nature paper.

This work was supported by the National Science Foundation through the Materials Research Science and Engineering Centers program and the Batteries for Advanced Transportation Program of the U.S. Department of Energy. It has been licensed by two companies. [The technology has already been licensed to two companies: the Belgian materials company Umicore, which makes the lithium particles, and a battery manufacturer.] [Ric Fulop, cofounder of Watertown battery company A123Systems, said his company had an option to license the technology. "From here to product takes a couple years, but it's very promising," Fulop said ].

Source

NPR INTERVIEW WITH Gerbrand Ceder

A123Systems Announces Plan to Build U.S.-based Lithium Ion Battery Mass Production Facilities

Planned $2.3 Billion facilities will support aggressive expansion plan to deliver energy storage systems to A123’s multiple OEM customers in the Electric and Hybrid Electric Vehicle market
Link

Nanoball Batteries Could Charge Electric Cars in 5 Minutes/MIT/Ceder, Kang

March 12th, 2009 by Lisa Zyga

Enlarge

A sample of the new battery material that could allow quick charging of portable devices. Image credit: Donna Coveney.

(PhysOrg.com) -- Researchers at MIT have designed a new battery that can recharge devices about 100 times faster than conventional lithium ion batteries. The design could lead to electric car batteries that charge in 5 minutes (compared with 8 hours in today's electric cars) and cell phone batteries that charge in just 10 seconds.

Byoungwoo Kang and Gerbrand Ceder of MIT have improved the design of a "nanoball battery," which has a cathode that is composed of nanosized balls of lithium iron phosphate. As the battery charges, the nanoballs release lithium ions that travel across an electrolyte to the anode. As the battery discharges, the opposite occurs, and the lithium ions are reabsorbed by the nanoballs in the cathode.

The key to the nanoball battery's quick charge time is the speed at which the lithium iron phosphate nanoballs in the cathode can release and absorb lithium ions. In conventional lithium ion batteries, detaching the ions from the normal cathode takes a relatively long time. By coating each nanoball with a thin layer of lithium phosphate, Kang and Ceder showed that they could detach the lithium ions from the nanoballs even quicker than previous studies have found.

To demonstrate the technology, the researchers fabricated a small battery that could be fully charged or discharged in 10 to 20 seconds, which would otherwise have taken six minutes. The scientists' tests showed that the new material degrades less than other battery materials after repeated charges and discharges. This means that the battery could be made with less material, which could possibly lead to smaller, lighter batteries.

More information: Byoungwoo Kang and Gerbrand Ceder. "Battery materials for ultrafast charging and discharging." Nature 458, 190-193 (12 March 2009), doi:10.1038/nature07853. [See below]

© 2009 PhysOrg.com

Letter

Nature 458, 190-193 (12 March 2009) | doi:10.1038/nature07853; Received 18 June 2007; Accepted 2 February 2009

Battery materials for ultrafast charging and discharging
Byoungwoo Kang¹ & Gerbrand Ceder¹

1. Department of Materials Science and Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA

Correspondence to: Gerbrand Ceder¹ Correspondence and requests for materials should be addressed to G.C. (Email: gceder@mit.edu).

The storage of electrical energy at high charge and discharge rate is an important technology in today's society, and can enable hybrid and plug-in hybrid electric vehicles and provide back-up for wind and solar energy. It is typically believed that in electrochemical systems very high power rates can only be achieved with supercapacitors, which trade high power for low energy density as they only store energy by surface adsorption reactions of charged species on an electrode material^{1, 2, 3}. Here we show that batteries^{4, 5} which obtain high energy density by storing charge in the bulk of a material can also achieve ultrahigh discharge rates, comparable to those of supercapacitors. We realize this in LiFePO₄ (ref. 6), a material with high lithium bulk mobility^{7, 8}, by creating a fast ion-conducting surface phase through controlled off-stoichiometry. A rate capability equivalent to full battery discharge in 10–20 s can be achieved.

New Shock Tech Could Zap Rioters, Cancer Cells

By David Hambling

March 09, 2009 | 12:41:44 PM

Today's Tasers stun their targets for just a few seconds. A new technique using ultra-short electric pulses could allow tomorrow's electroshock weapons to immobilize people for as long as fifteen minutes –- and may one day also be used to destroy tumors.

As I note in my latest New Scientist story, existing Tasers use an electric pulse that lasts a few microseconds, and delivers around .07 Joules of energy. This is sufficiently intense to disrupt nerve cell membranes, effectively paralyzing the neuromuscular system however tough you are. The microsecond pulses are repeated over a five-second cycle. According to Steve Tuttle of Taser International, the effects wear off almost immediately once the cycle finishes; he describes tests in which subjects have been able to carry out a task, such as pushing a specific button, immediately after being Tasered. [Others disagree, and point to all those times when coroners have ruled that the shock weapons contributed to someone's death. -- ed.]

Short-term incapacitation meets police requirements, allowing a suspect to be incapacitated for long enough to make a quick arrest. The U.S. military is looking at a longer keeping people stunned for much longer, however. The Joint Nonlethal Weapons Directorate is looking at a new generation of electroshock weapon that might knock the target down for fifteen minutes with a single ultra-short pulse.

Research is being carried out by the Frank Reidy Research Center for Bioelectrics at Old Dominion University. The Center's mission is to "to increase scientific knowledge and understanding of how electromagnetic fields and ionized gases interact with biological cells." A significant amount of their funding is military; the Center notes that their largest award was $5 million from Air Force Office of Scientific Research.

The key to the technology lies in using short pulses, which can have very different effects than the longer ones. When an electric field is applied to a cell, a charge starts to build up on the cell membranes. After a few microseconds, the charge is so high that holes (or "pores") start to form in the cell wall, an effect called electroporation. This allows material (in particular calcium ions) to pass through, affecting the function of the cell. With shorter pulses there is not enough time to affect the cell. But electroporation can affect the structures within the cell such as the nucleus, known as organelles.

"Because the organelles are much smaller than the cell itself... they reach their maximum charge much more quickly," Center founder Karl H. Schoenbach explains in an article. " Ending the pulse after the organelles are charged up, within a few hundred nanoseconds but before large pores appear in the cell’s own membrane, lets you focus the electric field’s effects on the organelles, such as the nucleus, while leaving the cell membrane relatively untouched. That, in turn, lets you do the complex and varied things medical science is interested in, such as killing tumor cells or triggering an immune system response."

So on the one hand ultra-short pulses can be used to selectively destroy cancerous cells. But they can also produce much more effective stunning effects.

A paper from the Center on Neuromuscular disruption with ultrashort electrical pulses compares 450-nanosecond pulses with multi-microsecond Taser pulses and found that the shorter pulses were more effective for suppressing voluntary movement, and used less energy. Another study found that even shorter, 60-nanosecond pulses could stun rats.

But the most significant is a paper which found that it was possible to incapacitate cells for a prolonged period -- "our study provides experimental evidence that even a single 60-ns pulse at 12 kV/cm can cause a profound and long-lasting (minutes) reduction of the cell membrane resistance (Rm), accompanied by the loss of the membrane potential." The paper says that cells could be prevented from functioning for fifteen minutes. These are early days, but researchers have suggested that a single ultrashort shock could leaving the target immobilized for "tens of minutes" using far less energy than a Taser pulse.

Obviously there are concerns over what other effects ultrashort pulses might have on the body.

"We have been advised by contacts who track the development of this type of technology that the medical and biological effects of such ultra-short electrical shocks in such a weapon are presently unknown," says Angela Wright of Amnesty International. "Stringent testing, before deployment, of the medical effects of such a weapon should take place."

"Studies are being conducted to examine the ion transport mechanisms and the effects on long term cell viability," says David B. Law of the JNLWD. He says that plans for tests on live animals are under way, but declined to comment on when human tests might happen -- if ever.

Source

Man who co-discovered HIV accused of stealing rights to Aids cure

A Nobel prize-winning French researcher who co-discovered the virus that leads to Aids but sparked controversy after his colleague said he had claimed all the glory, has now been accused of stealing the rights to a revolutionary invention that may provide a cure to the disease, it emerged yesterday.

By Henry Samuel in Paris

Last Updated: 3:58PM GMT 09 Mar 2009

Prof Luc Montagnier is locked in a legal battle with inventor Bruno Robert over the intellectual property rights to a technique whereby the Aids virus and other serious ailments, including Parkinson's and Alzheimer's disease, can be pinpointed by their electromagnetic "signatures".

The hope is that once identified, the diseases can be blocked or neutralised with an opposite electromagnetic signal.

Mr Robert, 47, approached Mr Montagnier in May 2005 with his work on electromagnetic waves. In November of that year, Mr Bruno registered a patent for the process of homing in on a "biochemical element presenting a biological activity through the analysis of low-frequency electromagnetic signals." A month later, France's patents body, Inpi, was surprised to a request for the very same patent from Prof Montagnier.

Last Tuesday, Prof Montaignier took Mr Bruno to court, claiming the intellectual property rights over the discovery. The verdict is due on 20 May.

Mr Bruno's lawyer alleged in Le Journal du Dimanche that Prof Montagnier had already admitted that he had not come up with the discovery, as he had signed a contract to use Mr Bruno's technique in 2005 in exchange for 100,000 euros per year over a five-year period. Mr Bruno never received any payment. Prof Montagnier's lawyer said the pair had only signed a "protocol agreement" which was not legally binding.

Prof Montagnier was awarded a Nobel prize last year for discovering the virus that leads to Aids along with Françoise Barré-Sinoussi. A third researcher, Jean-Claude Chermann received no award despite being hailed by peers as a key driving force in the lab.

Prof Chermann accused his former colleague of squeezing him out by intense lobbying. "Frankly, Montagnier, everyone laughs about him," he told Le Monde. "He followed communication lessons, cut his moustache, put on a little waistcoat...He played the mandarin like hell. I, for one am not a (re)searcher, I'm a finder," he said.

Source

Ref:
Montagnier patent filing
Robert patent filing

Sonodynamic Therapy (SDT)

The photodynamic agent we use is also sensitive to ultrasound frequencies. This approach allows deeper penetration into the body. Sonodynamic therpay is carried out using a simple therapeutic ultrasound machine with especially designed treatment head known as maniple, which is applied over the affected area with some ultrasound gel placed on the skin. This is done after the light bed exposure.

We are combining Photodynamic therapy with Sonodynamic therapy. This uses low-level ultrasound, which kills cancer cells using a non-thermal effect, especially cavitation. The agent we use is sensitive to the ultrasound frequency we use, which is 1 Mhz. Following the light bed exposure (Photodynamic Therapy), the ultrasonic probe, covered with ultra sound gel, is moved over the skin on the area nearest to the main tumour mass. The use of ultrasound enables us to penetrate significantly deeper into the body than we would otherwise be able to do. (see a review of research into the uses of low level ultra sound in cancer therapy, Uyu, Wang & Mason in Ultra Sonics Sonochermistry, Vol 11, issue 2, April 2004, pages 95-130).

Most photosensitizers come from a class of naturally occuring compounds called porphorins. Natural porphorins are breakdown products from recycled haemoglobin and are inherently light sensitive. These accumulate in tumours and cause cancer cells to auto-fluoresce. The first generation of photosensitizer approved for use in cancer treatment - Photofrin, - is derived from haemoglobin, whilst some of the more advanced agents are chlorophyll derivatives.

PDT has several advantages over surgery and radiotherapy; it is comparatively non-invasive, it can be targeted accurately and repeated dosages can be given without the total dose limitations associated with radiotherapy, and the healing process results in little or no scarring. PDT can always be done on an out-patient or day case setting, and it has no side serious effects.

The next generation of Photodynamic Therapy is a significant advance on previous PDT. This uses a specific extract of Chlorophyll A (trade name Ausclorin) which does not have to be given intravenously and can be given orally. It accumulates selectively in tumour sites and it does not persist in the skin. Photofrin does persist, so long term photosensitivity can develop lasting as long as 90 days. With the new preparation, the agent is cleared from the skin within 24 to 48 hours, so no photosensitivity occurs. Ausclorin and previous photosensitizers can use the laser, or a specialised light consisting of light emitting diodes, emitting in the red light region and the infra-red region of the spectrum or with light beds using fluorescent tubes in the red light region for whole body treatment.. Because the breakdown wave lengths of Ausclorin also occur in the infra-red region, this means that with the infra-red lights, penetration can occur as deep as twelve inches into the body, so deep tumours can be treated from the surface. This therefore makes it a non-invasive whole body treatment. The treatment programme can be repeated as often as is necessary, and for advanced tumours it is best to treat slowly so as to avoid too rapid a tumour break down in too short a period of time.

METHOD OF TREATMENT USING SONODYNAMIC THERAPY (SDT) AND AUSCLORIN PHOTODYNAMIC THERAPY (PDT):

The patient is assessed clinically. Then a dose of Ausclorin is calculated based on the patient's weight and stage of the tumour. This is taken orally each morning before breakfast whilst the Ausclorin clears from the skin and accumulates selectively in tumour sites. Following this the patient is exposed to the appropriate lights. The time of exposure is important, and can vary from up to 60 minutes for patients with less advanced tumours, to only a few minutes with patients with more advanced tumours (the more advanced the tumour, the slower the treatment programme).

Further light bed exposure is then calculated on an on-going clinical basis. The patient is given enough Ausclorin for treatment at the clinic and three months treatment at home.

Anecdotally there has been success using PDT with breast cancer and prostate cancer. There have been encouraging results with several types of brain tumour including glioblastoma multiforme, and many brain tumours significantly regressed during photodynamic therapy. One case of glioblastoma multiforma showed a total dissappearance of tumour.

We often combine ozone autohaemotherapy with PDT. PDT relies on the production of singlet oxygen (O). This is derived from oxygen (O2). Tumours are characteristically hypoxic (showing low oxygen lavels). Ozone autohaemotherapy is an effective way of increasing oxygenation just before light bed exposure, therefore increasing the effectiveness of PDT.

SCIENTIFIC INFORMATION REGARDING NEXT GENERATION PHOTODYNAMIC THERAPY

The fluorescent camera can display tumours near the surface of the body. This is often as good as, if not better than the latest scans known as PET scans (position emission tomography).

BRIEF SUMMARY OF RESULTS FOR TEN RECENT CONSECUTIVE PATIENTS IN A COLLEAGUES CLINIC WHO HAS USED SDT OVER THE PAST 12 MONTHS:

1. Stage III breast cancer. Primary breast tumour plus metastases in the axillary lymph node, the other breast and the liver. After PDT and lumpectomy: no evidence of cancer in all four sites.

2. Stage IV breast cancer with rampant body metastases. Very low energy, not enough to work in the garden. In bed by 7:30pm. After PDT (ongoing) weight increased 3kg and now normal. Normal sleeping time and energy levels. Resumed gardening. Scan shows that the tumours have stopped spreading.

3. Metastatic melanoma grade IV. ABout 80 metastases visible. Oncologist predicted 2 more months of life. After PDT (ongoing), Alive and well 4 months after prediction. Metastases down to about 20. Energy, appetite and weight improved. Physician estimates that about 80% of the cancer is gone. Further treatment needed.

4. Prostate cancer (large tumolur mass), grade IV, urinary infections, bowel infections, Inability to urinate without catheter, impotent. After SDT/PDT (ongoing) Prostate shrinking and softening, urination better, impotence easing. Needs further treatment but improving.

5. Ovarian cancer Grade IV. Had hysterectomy and other surgery. No symptoms other than elevated cancer marker. After pDT cancer marker now normal. No evidence of cancer.

6. Squamous cell carcinoma grade 1. Lump on upperlip removed surgically. PDD showed 6 metastases on upper lip. After SDT all metastases have disappeared..

7. Prostate grade IV. Hard prostate with 2 nodules, metastasized outside the gland. After SDT (ongoing) Prostate shrunk, softened, one nodule disappeared. Better urination. Clear or almost clear of cancer.

8. Mesothelioma lung cancer. Symptoms include coughing at night, disturbed sleep. Painful breathing, not allowing deep inhalations. Photodynamic diagnosis showed over 12 metastases in the thorax. No noticable benefits from chemotherapy. After SDT (ongoing): Coughing at night has stopped, giving much better sleep. Breathing not as painful, allowing deeper inhilation. "I have an amazing increase in energy". Visible metastases have dropped from 12 or more to one.

9. Breast cancer grade IV. Lumpectomy. PDD showed metastases in the breast and the axillary lymph nodes. After SDT (ongoing) Cleared metastases from the breast. Those in the lymph glands remain. Next treatment will be PDT/SDT.

10. Breast cancer grade IV with extensive liver metastases. PDT failed to hault the progress of the illness. SDT was not available at the time and she has chosen other treatment.

Source

Ausclorin

Effect of Chlorin Structure on Theoretical Electronic Absorption Spectra and on the Energy Released by Porphyrin-Based Photosensitizers

Abstract

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Marcela Palma^†, Gloria I. Crdenas-Jirn*^† and M. Isabel Menndez Rodrguez*^‡

Laboratorio de Qumica Terica, Departamento de Ciencias del Ambiente, Facultad de Qumica y Biologa, Universidad de Santiago de Chile, USACH Casilla 40, Correo 33, Santiago, Chile, and Departamento de Qumica Fsica y Analtica, Facultad de Qumica. Universidad de Oviedo, C/Julin Clavera 8, 33006 Oviedo, Asturias, Spain

J. Phys. Chem. A, 2008, 112 (51), pp 13574–13583

DOI: 10.1021/jp804350n

Publication Date (Web): November 24, 2008

Copyright © 2008 American Chemical Society

†

Universidad de Santiago de Chile.

,

* Authors to whom correspondence should be addressed: e-mail gloria.cardenas@usach.cl (G.I.C.-J.) or isabel@uniovi.es (M.I.M.R.).

,

‡

Universidad de Oviedo.

Abstract

In this work eight porphyrins (p) and eight chlorins (c) are theoretically characterized [BLYP/6-31G(d)] in their singlet and triplet states. Nine of them (1_p, 1_c, 2_p, 3_p, 4_p, 5_p, 6_c, 7_c, and 8_c) have already been synthesized and are in trial use in photodynamic therapy (PDT). The seven remaining were built up as chlorins analogous to porphyrins 2_p−5_p and porphyrins analogous to chlorins 6_c−8_c. The aim is to investigate the effect of the chlorin structure on the Q-band of electronic spectra at BLYP/6-31G(d) (gas phase, methanol solution) and at BHANDHLYP/6-31+G(d) (methanol solution), and on the triplet → singlet energy emission, as these two factors determine the quality of a good photosensitizer. It is found that meso substituents lead to greater geometry distortions than β-substituents in both porphyrins and chlorins and in both singlet and triplet states. In methanol solution, chlorin-like structures with β substitution present significantly red-shifted Q-bands in comparison with their porphyrin analogues, so they would be better photosensitizers than porphyrins. Concerning to the triplet → singlet energy emission calculated in methanol solution, three porphyrins (4_p, 6_p, and 8_p) and all the studied substituted chlorins could be useful to generate active ¹O₂. 4_c would be the best photosensitizer, as it absorbs the largest wavelength in the therapeutic window (approximately 690 nm) and releases the amount of energy closest to the required one (1.22 eV).

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New Target Against Flu Virus May Extend Vaccine Potency

Antibody Uncovers Vulnerability of Protein Stem

HMS researchers have found an Achilles heel in the influenza virus that may someday make annual flu shots a thing of the past. By targeting a hidden pocket in the microbe with a newly discovered antibody, they disabled a wide range of viruses, including those that cause the avian flu and the virulent 1918 Spanish flu.

While this research could lead to clinical trials of a new antiviral as soon as 2012 and may eventually lead to a more durable influenza vaccine, its influence may extend even further. The work, described in the March Nature Structural and Molecular Biology, validates a novel approach to finding such viral vulnerabilities and reveals what may be a more general principle for defeating a variety of pathogens.

Photo by Graham Ramsay

Wayne Marasco and Jianhua Sui have discovered influenza’s Achilles heel and devised a method to attack it.

---

Striking Gold
The story begins in the lab of Wayne Marasco, HMS associate professor of medicine at the Dana–Farber Cancer Institute. Twelve years ago, Marasco collected blood from 57 healthy Bostonians and used the samples to create a library of 27 billion different human antibodies.

Researchers “pan” the library by presenting it with an antigen, such as a whole virus or a protein on the viral surface. Panning unearths antibodies that bind to that antigen. Marasco used his library to isolate an antibody against SARS in 2004.
When the avian flu appeared, Marasco and first author Jianhua Sui put the library to work again. But instead of panning with the whole H5N1 influenza virus, they focused on a single protein. They isolated the H5 version of hemagglutinin, a surface protein on influenza that allows the virus to invade a cell and replicate. (The N portion is a different surface protein called neuraminidase, which allows the virus to exit the cell.) The effort uncovered 10 potential antibodies.

Sui and Marasco, in partnership with co-author Rubin Donis, chief of the molecular virology and vaccines branch of the Centers for Disease Control and Prevention, tested three of these antibodies in mice infected with a lethal dose of avian flu. The antibodies neutralized between 80 and 100 percent of the infections.

Unexpectedly, the antibodies also neutralized other strains. They knocked down H1N1 (the 1918 Spanish flu), H2N2, H6N1 and more. “It became apparent very quickly that the target they were recognizing was highly conserved,” said Marasco.

Not only were these antibodies more broadly effective than expected, they also worked differently. Most antibodies stick to the round top of the lollipop-shaped hemagglutinin protein and interfere with the protein’s ability to bind to the cell membrane. But Marasco and Sui’s antibodies were not blocking the membrane binding. “That told us right there that the antibody wasn’t working against the globular head,” said Marasco.

Stemming the flu. Each year, scientists develop new influenza vaccines to target the ever-mutating globular heads (light red) of the hemagglutinin proteins that coat the virus. A newly discovered antibody binds to the much less variable and much less accessible stem of the protein (red). Work is under way to turn this antibody into an antiviral that can be used to contain a pandemic and to protect immunosuppressed individuals during flu season. Since the machinery of the stem evolves more slowly than the head, the discovery may lead to a broadly effective influenza vaccine that lasts for longer than a single season.

---

At this point, a third part of the team became critically important. Robert Liddington and his team at the Burnham Institute for Medical Research crystallized one of the antibodies bound together with hemagglutinin. “That’s when the revelations started coming,” said Marasco.

The crystal confirmed that the antibody was not bound to the enticing top of the protein, but rather to a pocket in the stem. That pocket contains complex machinery. It houses three entangled moving parts that allow the virus to infect the cell (see video). The crystal revealed that the antibody grabs onto all three and prevents that machinery from working. “In the past, people didn’t even know to look in that pocket,” said Sui.

Sui took this information and used it to search a database of more than 6,000 (and growing) known genetic variants of the flu. She found that only two versions of this complex stem-based machinery have evolved. An examination by Liddington’s team of crystal structures of known variants found the same. The antibodies Sui and Marasco found work against one version. They are now running the other version of the stem through the same panning process to find an antibody against it.

Enduring Weakness
The contrast between the slow evolution of the stem and the impossible-to-keep-up-with evolution of the head is stunning. But it is not surprising. The part of the headpiece that binds to the cell membrane is very small, said Sui. So the rest of the headpiece can change dramatically without compromising the function.

But in the stem, “the delicate and complex machinery is highly conserved,” said Donis. “The virus cannot mutate it because by doing so, it would commit suicide.” Indeed, Donis’s team attempted to force mutations in the stem, but none emerged.

In discovering this new, hidden vulnerability, the researchers have realized that the virus has been fooling them, and our bodies, all along. “The virus has very cleverly developed an area on the top of its coat protein that creates a molecular decoy,” said Marasco. He speculates that the immune system mounts a full-scale attack against the easy-to-spot decoy while it simultaneously suppresses any efforts to target the elusive stem. Similarly, new vaccines chase the decoy each season hoping to hit it just right.

DOUBLE CLICK PIC FOR VIDEO

Courtesy Dana–Farber Cancer Institute

HMS researchers are targeting a common weakness to tackle influenza.

Courtesy Dana–Farber Cancer Institute

HMS researchers are targeting a common weakness to tackle influenza.

---

But now, with the new insights from this work, “a pan-therapy for all kinds of influenza may be within our grasp,” said Liddington. Further, Marasco suspects that the influenza virus’s means of protecting its most vulnerable machinery may be a more general strategy. He has observed almost the exact same system in corona viruses, such as SARS.

Assuming that approval for human testing proceeds without a hitch, the new influenza antibody will likely be used as an antiviral first. Since it is unlikely that a mutant will evolve to defeat it, the hope is that this antiviral can be stockpiled and stored for years. Marasco also speculates that it may be possible to develop a vaccine that both masks the decoy and allows the immune system to attack the less flexible stem.

In the future, Marasco plans to apply these same methods to other viruses. The team’s approach not only allows them to find novel antibodies and hidden targets, it also helps researchers respond nimbly as resistant strains evolve.

—Elizabeth Dougherty

Students may contact Wayne Marasco at wayne_marasco@dfci.harvard.edu for more information.

Conflict Disclosure: The authors report no conflicts of interest.

Funding Sources: National Institutes of Health

Source

Quest PharmaTech reports encouraging results from study of cancer therapy

Fri. March 06, 2009; Posted: 07:04 AM

Mar 06, 2009 (Datamonitor via COMTEX) -- QPTFF | Quote | Chart | News | PowerRating -- Quest PharmaTech, a drug development company, has announced promising results from a study designed to investigate the effectiveness of its proprietary SL052 for photodynamic therapy used in combination with immunotherapeutic agents in solid tumor animal models.

The study, conducted by Mladen Korbelik at the BC Cancer Agency in Vancouver, has demonstrated that SL052 increased the potency and effectiveness of immunotherapeutic agents when used in combination with SL052 photodynamic therapy (PDT).

According to the company, the results also confirmed that SL052 was an effective and well tolerated photosensitizer for PDT ablation of two highly tumorigenic, solid murine tumors. Further, the results demonstrated that photodynamic therapy generated direct local cytotoxicity and induced a systemic immune response, which could enhance its therapeutic effect on both primary tumors and metastases at distant sites.

The study tested several applications of SL052 and evaluated host recognition and immunological destruction of solid tumors. The results indicate the potential of SL052 PDT for use in combination with cancer vaccines to generate a superior immune response compared with vaccines alone.

The study also revealed that SL052 PDT may be effectively combined with either single or multiple-complementary effectors of the host's immune response to substantially boost the frequency of permanent cures, the company added.

Madi Madiyalakan, CEO of Quest, said: "These results further define the therapeutic profile of SL052. While its activation through either photodynamic or sonodynamic therapy was already established, we now have a clear indication of its potential to act as either an immune response stimulator or as a cancer vaccine. Taken together, these characteristics of SL052 provide a new potential treatment modality for cancer therapy."

For full details for QPTFF click here.

Source

(WO/2009/026724) SYSTEM AND APPARATUS FOR SONODYNAMIC THERAPY

Biblio. Data

• Description
• Claims
• National Phase
• Notices
• Documents

Pub. No.: WO/2009/026724 International Application No.: PCT/CA2008/001548 Publication Date: 05.03.2009 International Filing Date: 29.08.2008
IPC:	A61N 7/00 (2006.01)
Applicants:	ANGEL SCIENCE & TECHNOLOGY (CANADA), INC. [CA/CA]; 4936 Yonge Street, Suite 260, Toronto, ON M2N 6S3 (CA) (All Except US). CHEN, Rixin [CA/CA]; (CA) (US Only).
Inventor:	CHEN, Rixin; (CA).
Agent:	DEETH WILLIAMS WALL LLP; 400-150 York Street, Toronto, Ontario M5H 3S5 (CA).
Priority Data:	11/849,179 31.08.2007 US

Title:

SYSTEM AND APPARATUS FOR SONODYNAMIC THERAPY >>>>>>>>>>>>>>>>>>>>>>>>>>>>>Click pic to enlarge

Abstract:

The present invention relates to diffuse ultrasound along with chemical agents to treat tissue, called sonodynamic therapy (SDT), and a system for treatment using SDT that comprises a whole body ensonification apparatus and control system. The whole body ensonification may reduce the chances of missing desired tissue that may not be easily detectable or may be found throughout the body. The apparatus has a plurality of diffuse ultrasound transducers for ensonifying at least part of a chamber filled with fluid and designed to accommodate a body for treatment. The person may be treated with sono-sensitive chemical agents, which may be activated when ensonified by the apparatus.

Source

US Filing

United States Patent Application	20090062724
Kind Code	A1
Chen; Rixen	March 5, 2009

---

SYSTEM AND APPARATUS FOR SONODYNAMIC THERAPY

Abstract

The present invention relates to diffuse ultrasound along with chemical agents to treat tissue, called sonodynamic therapy (SDT), and a system for treatment using SDT that comprises a whole body ensonification apparatus and control system. The whole body ensonification may reduce the chances of missing desired tissue that may not be easily detectable or may be found throughout the body. The apparatus has a plurality of diffuse ultrasound transducers for ensonifying at least part of a chamber filled with fluid and designed to accommodate a body for treatment. The person may be treated with sono-sensitive chemical agents, which may be activated when ensonified by the apparatus.

---

Inventors:

Chen; Rixen; (Vancouver, CA)

NOTES:
ANGEL SCIENCE & TECHNOLOGY (CANADA), INC.

Angel’s HIFU technology has been developed in conjunction with the China National Ultrasound Research Laboratory and the technology continues to be expanded and improved by its researchers and scientists today. Angel began first stage clinical trials in China in 2002. Successful and positive third stage clinical trials were completed at the end of 2005.
Source

Studies Show Combination Laser Therapy Effective At Clearing Acne, Reducing Oil Production

Posted : Thu, 05 Mar 2009 22:00:23 GMT

SAN FRANCISCO, March 5

AAD-lasertherapy-acne

Dermatologist evaluates the latest laser and light sources approved for treating acne

SAN FRANCISCO, March 5 /PRNewswire-USNewswire/ -- From the removal of childhood birthmarks to skin rejuvenation, laser technology has become a mainstay in dermatology. Now, dermatologists are fine-tuning this technology to safely and effectively treat one of the most common skin conditions that plagues teenagers and adults alike: acne.

Speaking today at the 67th Annual Meeting of the American Academy of Dermatology [AAD] (Academy), dermatologist Macrene Alexiades-Armenakas, MD, PhD, FAAD, assistant clinical professor of dermatology at Yale University School of Medicine in New Haven, Conn., presented scientific data illustrating how photodynamic therapy combined with a long-pulse, pulsed-dye laser and topical 5-aminolevulinic acid provides long-lasting clearance of acne lesions.

"Laser technology has made great inroads in the treatment of acne, which until recently has been treated almost exclusively - and with varying degrees of success - with topical, systemic and hormonal medications," said Dr. Alexiades-Armenakas. "Now, we have solid evidence-based medicine supporting the effectiveness of certain laser therapies as a long-term solution for treating active acne. The key is to distinguish the benefits and limitations of these available technologies and select the most effective treatments for each acne patient."

Photodynamic Therapy with a Photosensitizer
In a preliminary study, Dr. Alexiades-Armenakas examined whether a combination of photodynamic therapy (PDT) with a photosensitizer known as topical 5-aminolevulinic acid (ALA) and activated by long-pulse, pulsed dye laser could safely and effectively clear mild to severe cases of acne. PDT works by using laser or light energy - in this case a pulsed dye laser was used - to activate the ALA, which is a solution that penetrates into the oil glands and is applied to the skin one hour prior to treatment. As it penetrates, ALA binds to the oil glands and sensitizes the cells to light.

The 14 patients treated with ALA PDT received one to six treatments depending on the severity of their acne and continued to use topical medications during and after the study. The control group consisted of four patients who were either treated with conventional therapy (such as systemic or topical medications) or with laser energy but without ALA PDT.

Upon analyzing the data, Dr. Alexiades-Armenakas found that all (100 percent) of the 14 patients in the ALA PDT treatment group experienced complete clearance of their acne. She reported that an average of 2.9 ALA PDT treatments was administered to this patient group and improvement in the acne lesions was visible within one to two weeks after the first treatment. By comparison, none of the four patients in the control group who were treated with either laser energy alone or conventional therapy achieved complete clearance of their acne.

"The first-of-a-kind study found this particular form of photodynamic therapy used in conjunction with topical therapy to be the first such treatment to achieve complete clearance of acne up to 13 months post treatment and a 77 percent clearance rate per treatment. Four subsequent studies conducted by other investigators involving an additional 75 patients demonstrated similar results," said Dr. Alexiades-Armenakas. "Patients also experienced an added benefit of significant improvement in their acne scars, as the pulsed dye laser offers superior penetration to the deeper layers of the skin where scars form."
.....

Source

COMPOSITION AND METHOD FOR CANCER TREATMENT USING TARGETED SINGLE-WALLED CARBON NANOTUBES

United States Patent Application	20080227687
Kind Code	A1
Harrison; Roger G. ; et al.	September 18, 2008

Abstract

The present invention is a method for detecting and destroying cancer tumors. The method is based on the concept of associating a linking protein or linking peptide such as, but not limited to, annexin V or other annexins to single-walled carbon nanotubes (SWNT) to form a protein-SWNT complex. Said linking protein or peptide can selectively bind to cancerous cells, especially tumor vasculature endothelial cells, rather than to healthy ones by binding to cancer-specific external receptors such as anionic phospholipids including phosphatidylserine expressed on the outer surfaces of cancer cells only. Irradiation of bound SWNTs with specific wavelength is then used to detect and destroy those cells to which the SWNTs are bound via the linking protein or peptide thereby destroying the tumor or cancer cells.

---

Inventors:	Harrison; Roger G.; (Norman, OK) ; Resasco; Daniel E.; (Norman, OK)
Correspondence Name and Address:	DUNLAP CODDING, P.C. PO BOX 16370 OKLAHOMA CITY OK 73113 US
Serial No.:	033857
Series Code:	12
Filed:	February 19, 2008

U.S. Current Class:	514/2; 606/3
U.S. Class at Publication:	514/2; 606/3
Intern'l Class:	A61K 38/00 20060101 A61K038/00; A61B 18/18 20060101 A61B018/18

---

Claims

---

1. A method of treating a cancer tumor or cancer cells in a patient, comprising:

providing a composition comprising a protein-carbon nanotube complex comprising a protein or peptide operatively attached to a carbon nanotube, wherein the protein or peptide of the protein-carbon nanotube complex comprises a binding protein or peptide that has binding specific for an external receptor or binding site on a tumor vasculature endothelial cell or on a cancer cell;

administering the composition comprising the protein-carbon nanotube complex to the patient wherein the protein-carbon nanotube complex preferentially binds via the binding protein or peptide to the external receptor or binding site on an outer surface of the endothelial cell of the tumor vasculature of the cancer tumor or on an outer surface of the cancer cell in the patient; and

exposing the patient to electromagnetic radiation comprising a wavelength absorbable by the carbon nanotube causing elevation of the temperature of the carbon nanotube of the protein-carbon nanotube complex to a temperature which induces damage or death of the endothelial cell of the tumor vasculature or of the cancer cell to which the protein-carbon nanotube complex is bound.

[Snip from Description]
[0023]After treatment with the protein-SWNT complex or peptide-SWNT complex of the present invention, the tumor having the SWNTs bound thereto is then selectively exposed to electromagnetic radiation, for example, near-infrared (NIR) radiation. NIR radiation causes excessive local heating of SWNTs but does not otherwise affect biological systems which are not associated to the SWNTs (12). This excessive local heating of the SWNTs bound to the surface of endothelial cells of the tumor vasculature or to surfaces of the cancer cells leads to the destruction of the tumor vasculature or of the cancer cells and thus to the death or inhibition of growth of the tumor or cancer cells. Without wishing to be held to theory, it is believed that the killing of the tumor is by a combination of heating and cutting off the tumor's blood supply. In order to avoid damage to normal blood vessels, it is advantageous to delay the NIR treatment (or treatment with other wavelengths) until there is clearing of free SWNTs from the bloodstream such that substantially the only SWNTs in the body are those bound to the tumor vasculature or cancerous cells. The free SWNTs should clear within a matter of hours after administration. For example, in a recent study (30) with rabbits, SWNTs were injected into the bloodstream, and the SWNT concentration decreased exponentially with a half-life of 1.0.+-.0.1 hour. No adverse effects from low-level SWNT exposure could be detected from behavior or pathological examination.

Source

Note:
No --administering to the patient an immunostimulant to enhance the patient's immune response to antigens released from the cancer cells or tumor vasculature endothelial cells-- in this application. (See United States Patent Application 20090062785 below, for that.)

PAIR (to follow the USPTO prosecution history) - After the entry page - Insert '20080227687' in the box and select 'Publication Number'.

COMPOSITIONS AND METHODS FOR CANCER TREATMENT USING TARGETED SINGLE-WALLED CARBON NANOTUBES

United States Patent Application	20090062785
Kind Code	A1
Harrison, JR.; Roger G. ; et al.	March 5, 2009

Abstract

The present invention is a method for detecting and destroying cancer tumors. The method is based on the concept of associating a linking protein or linking peptide such as, but not limited to, annexin V or other annexins to single-walled carbon nanotubes (SWNT) to form a protein-SWNT complex. Said linking protein or peptide can selectively bind to cancerous cells, especially tumor vasculature endothelial cells, rather than to healthy ones by binding to cancer-specific external receptors such as anionic phospholipids including phosphatidylserine expressed on the outer surfaces of cancer cells only. Irradiation of bound SWNTs with one or more specific electromagnetic wavelengths is then used to detect and destroy those cells to which the SWNTs are bound via the linking protein or peptide thereby destroying the tumor or cancer cells and preferably an immunostimulant is provided to the patient to enhance the immune response against antigens released from the tumor or cancer cells.

---

Inventors:

Harrison, JR.; Roger G.; (Norman, OK) ; Resasco; Daniel E.; (Norman, OK)

Claims1. A method of treating a cancer tumor or cancer cells in a patient, comprising:providing a composition comprising a protein-carbon nanotube complex comprising a protein or peptide operatively attached to a carbon nanotube, wherein the protein or peptide of the protein-carbon nanotube complex comprises a binding protein or peptide that has binding specific for an external receptor or binding site on a tumor vasculature endothelial cell or on a cancer cell;

administering the composition comprising the protein-carbon nanotube complex to the patient wherein the protein-carbon nanotube complex preferentially binds via the binding protein or peptide to the external receptor or binding site on an outer surface of the endothelial cell of the tumor vasculature of the cancer tumor or on an outer surface of the cancer cell in the patient;

exposing the patient to electromagnetic radiation comprising a wavelength absorbable by the carbon nanotube causing elevation of the temperature of the carbon nanotube of the protein-carbon nanotube complex to a temperature which induces damage or death of the endothelial cell of the tumor vasculature or of the cancer cell to which the protein-carbon nanotube complex is bound; and

administering to the patient an immunostimulant to enhance the patient's immune response to antigens released from the cancer cells or tumor vasculature endothelial cells.

[Snip from Description]
[0027]After treatment with the protein-SWNT complex or peptide-SWNT complex of the present invention, the tumor having the SWNTs bound thereto is then selectively exposed to electromagnetic radiation, for example, radio frequency radiation, near-infrared (NIR) radiation, visible light, or UV radiation. The energy level of NIR radiation can be adjusted to give excessive local heating of SWNTs but not otherwise affect biological systems which are not associated to the SWNTs (12). This excessive local heating of the SWNTs bound to the surface of endothelial cells of the tumor vasculature or to surfaces of the cancer cells leads to the destruction of the tumor vasculature or of the cancer cells and thus to the death or inhibition of growth of the tumor or cancer cells. Without wishing to be held to theory, it is believed that the killing of the tumor is by a combination of heating and cutting off the tumor's blood supply. In order to avoid damage to normal blood vessels, it is advantageous to delay the NIR treatment (or treatment with other wavelengths) until there is clearing of free SWNTs from the bloodstream such that substantially the only SWNTs in the body are those bound to the tumor vasculature or cancerous cells. The free SWNTs should clear within a matter of hours after administration. For example, in a recent study (30) with rabbits, SWNTs were injected into the bloodstream, and the SWNT concentration decreased exponentially with a half-life of 1.0.+-.0.1 hour. No adverse effects from low-level SWNT exposure could be detected from behavior or pathological examination.

Source

Notes:
Resasco; Daniel E. is Chief Scientist and Founder of SouthWest NanoTechnologies, Inc. (SWeNT)

IP for Harrison; Roger G
US Patent filings
US Patents

Quest PharmaTech - Photosensitizer SL052

Quest PharmaTech Announces Results Showing its Photosensitizer, SL052, is an Effective Immuno-Stimulant when combined with Immunotherapy for the Removal of Solid Tumors

Wednesday, March 4, 2009, 12:36 pm EST

TSX Venture: QPT - QUEST PHARMATECH INC. (Tier2) (QPT.V) QUOTES

11 Year Chart

IP
EPO
WIPO WO/2008/011707 WO/2007/016762

EDMONTON, March 4 /CNW/ - Quest PharmaTech Inc. (TSX-V: QPT - News), ("Quest" or the "Company") a pharmaceutical company developing and commercializing products for the treatment of cancer and dermatological conditions, today announced results from a study designed to investigate the effectiveness of its proprietary SL052 for photodynamic therapy (PDT) used in combination with immunotherapeutic agents in solid tumor animal models. The study, conducted by Dr. Mladen Korbelik at the BC Cancer Agency in Vancouver, demonstrated that SL052 increased the potency and effectiveness of immunotherapeutic agents when used in combination with SL052 PDT.

The results also confirmed that SL052 was an effective and well tolerated photosensitizer for PDT ablation of two highly tumorigenic, solid murine tumors. Further, the results demonstrated that photodynamic therapy generated direct local cytotoxicity and induced a systemic immune response, which could enhance its therapeutic effect on both primary tumors and metastases at distant sites.

The study tested several applications of SL052 and evaluated host recognition and immunological destruction of solid tumors. The results indicate the potential of SL052 PDT for use in combination with cancer vaccines to generate a superior immune response compared with vaccines alone. The study also revealed that SL052 PDT may be effectively combined with either single or multiple-complementary effectors of the host's immune response to substantially boost the frequency of permanent cures.

"The effects of immunotherapy can be amplified when combined with photodynamic therapy, potentially making immunophotodynamic therapy a superior systemic cancer treatment modality," said Thomas Woo, Vice President of Product Development at Quest.

SL052 is a non-toxic agent with broad potential to treat a variety of solid tumors using photodynamic (light activation) therapy or sonodynamic (ultrasound activation) therapy. Photodynamic therapy is applicable for superficial level solid tumors and sonodynamic therapy targets more deeply seated solid tumors.

"These results further define the therapeutic profile of SL052," stated Dr. Madi R. Madiyalakan, Chief Executive Officer at Quest. "While its activation through either photodynamic or sonodynamic therapy was already established, we now have a clear indication of its potential to act as either an immune response stimulator or as a cancer vaccine. Taken together, these characteristics of SL052 provide a new potential treatment modality for cancer therapy."

About SL052

SL052 is a member of Quest PharmaTech's SonoLight Portfolio with the potential to reduce or eliminate the side effects associated with currently available cancer treatment modalities: surgery, chemotherapy and radiotherapy. Its properties of activation with harmless physical agents (light and ultrasound), combined with its ability to generate cancer vaccines and stimulate an anti-cancer immune response warrant further development in a broad-spectrum oncology arena. With these results, the next development stage for SL052 is a Phase I clinical trial for the treatment of Prostate Cancer. Quest is presently awaiting approval from Health Canada that will allow it to initiate a Phase I clinical trial for SL052.

About Quest PharmaTech Inc.

Quest is a publicly traded, Alberta-based pharmaceutical company committed to the development and commercialization of new pharmaceutical products. It is developing a series of products for the treatment of cancer and dermatological conditions based on its unique photodynamic and sonodynamic therapy platforms.

     Neither TSX Venture Exchange nor its Regulation Services Provider (as
that term is defined in the policies of the TSX Venture Exchange) accepts
responsibility for the adequacy or accuracy of this release.

For further information

Dr. Madi R. Madiyalakan, Chief Executive Officer, Quest PharmaTech Inc., Tel: (780) 448-1400 Ext. 204, Email: madi@questpharmatech.com, Internet: www.questpharmatech.com
Media and Investor Relations, Adam Peeler, The Equicom Group Inc., Tel: (416) 815-0700 Ext. 225, Email: apeeler@equicomgroup.com

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New Type Of Vaccination Provides Instant Immunity To Two Types Of Cancer In Animal Model

ScienceDaily (Mar. 4, 2009) — The experiments, thus far performed only in mice, appear to overcome a major drawback of vaccinations – the lag time of days, or even weeks, that it normally takes for immunity to build against a pathogen. This new method of vaccination could potentially be used to provide instantaneous protection against diseases caused by viruses and bacteria, cancers, and even virulent toxins.

The team, led by Scripps Professor Carlos Barbas, III, Ph.D., tested the vaccination method – called covalent immunization – on mice with either melanoma or colon cancer.

The scientists injected these mice with chemicals specifically designed to trigger a programmable and "universal" immune reaction. They developed other chemicals, "adapter" molecules," that recognized the specific cancer cells. Once injected into the animal, the adapter molecules self-assembled with the antibodies to create covalent antibody-adapter complexes.

"The antibodies in our vaccine are designed to circulate inertly until they receive instructions from tailor-made small molecules to become active against a specific target," Barbas says. "The advantage of this method is that it opens up the possibility of having antibodies primed and ready to go in the time it takes to receive an injection or swallow a pill. This would apply whether the target is a cancer cell, flu virus, or a toxin like anthrax that soldiers or even civilian populations might have to face during a bioterrorism attack."

Only those mice that received both the vaccine and the adapter compound generated an immediate immune attack on the cancer cells that led to significant inhibition of tumor growth. This is the first time that such a covalent vaccine has been successfully designed and tested – typically, antibodies do not bind to chemicals in this covalent fashion.

The current breakthrough builds on work the Barbas laboratory has been engaged in for the past few years on chemically programmed monoclonal antibodies, a new class of therapeutics that the group invented. In this type of therapy, small, cell-targeting molecules and non-targeting catalytic monoclonal antibodies self-assemble to target pathogens. Monoclonal antibodies are produced in the laboratory from a single cloned B-cell – the immune system cell that makes antibodies – to bind to a specific substance. Three clinical trials are now under way by Pfizer to test the therapeutic effectiveness of this new type of therapy in cancer and diabetes. The antibodies in the antibody-adapter complex are monoclonal antibodies engineered to link themselves to adapter molecules.

The Search for the Ideal Vaccination

The practice of vaccination has been extraordinarily successful in controlling certain diseases, but there are drawbacks. Vaccine development can be an educated guessing game – in the case of the flu, for example, scientists must study worldwide outbreak patterns to anticipate which type of flu might strike a particular area. In addition, the most common vaccination strategies use whole proteins, viruses, or other complex immunogens – not just the specific part of the macromolecule that is recognized by the immune system – to elicit an immune response, which makes for wasted immune activity. Then there is the body's own kinetics – the time it takes to mount a disease-relevant immune response to immunogens limits the speed with which immunity can be achieved. Finally, age-related declines in the ability to mount strong immune responses to biological-based vaccines present another challenge to the effectiveness of such vaccines.

Barbas's chemical-based – rather than biological based – approach to vaccine development addresses many of these challenges.

"Our approach differs from the traditional vaccine approach in the sense that when we design an antibody-adapter compound we know exactly what that compound will react with," Barbas says. "The importance of this is best exemplified with HIV. In current vaccines, many antibodies are generated against HIV, but most are not able to target the active part of the virus."

In the near term, Barbas will apply his covalent vaccination approach to HIV, cancer, and infectious diseases for which no vaccines currently exist. A particular focus will be creating adapter molecules specific to these diseases.

"We believe that chemistry-based vaccine approaches have been underexplored and may provide opportunities to make inroads into intractable areas of vaccinology," Barbas says.

The study was funded by the Skaggs Institute for Chemical Biology and the National Institutes of Health.

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Journal reference:

1. Mikhail Popkov et al. Instant immunity through chemically programmable vaccination and covalent self-assembly. Proceedings of the National Academy of Sciences, March 2, 2009

Adapted from materials provided by Scripps Research Institute.

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Preying On a Tumor's Weakness With Nanotechnology to Fight Cancer

Winner of this year's $30,000 Lemelson-MIT Student Prize uses gold nanoparticles to kill malignancies but spare healthy tissue

By Larry Greenemeier

GEOFFREY VON MALTZAHN: The 28-year-old Ph.D. candidate has won this year's $30,000 Lemelson-MIT Student Prize for his work developing ways to use nanotechnology to fight cancer.
COURTESY OF HARVARD-MIT DIVISION OF HEALTH SCIENCES AND TECHNOLOGY

The Harvard-MIT Division of Health Sciences and Technology (HST) today named Geoffrey von Maltzahn this year's recipient of the $30,000 Lemelson-MIT Student Prize for developing a technique that utilizes nano-sized gold particles to target malignant tumors and kill cancer cells while leaving healthy tissue unscathed. Established in 1994, the award is given out annually to an MIT senior or graduate student who has contributed significantly to the fields of science or technology.

The approach capitalizes on "tumors behaving like tumors," says von Maltzahn, a 28-year-old Ph.D. candidate, and so, triggering the growth of as many new blood vessels as quickly as possible to nourish and help them thrive. But instead of feeding these tumors, von Maltzahn relies on these ultra-porous nascent blood vessels to transport rod-shaped gold nanoparticles injected into cancer patients to the tumor, where they latch onto malignant tissue.

Although other researchers have tested the use of nanoparticles to fight cancer (read about another MIT/Harvard effort here), Von Maltzahn has developed two ways to attack tumors once the nanoparticles have set up shop there. The first is to shine a near-infrared laser on the patient's skin above the malignancies; the light heats the gold to high enough temps to interrupt and destroy cancer cells with minimal if any damage to surrounding healthy cells. In pre-clinical mouse trials a single nanoparticle injection (which includes trillions of nanoparticles) eradicated 100 percent of tumors when combined with near-infrared light. The problem with current radiation therapy is that in most cases it is not confined to malignant growths and healthy tissue gets caught in the crossfire, according to von Maltzahn.

His other award-winning technique involves two injections: the first batch are sent out as scouts to identify and attach to tumors, where they serve as markers for a second battalion of nanoparticles covered with cancer-fighting agents that home in on and destroy the tumors but ignore healthy tissue. In mouse trials, von Maltzahn and his colleagues found that this "scout-assassin" system successfully delivered doses of medicine in mice that were more than 40-times more potent and much more successful at killing tumors than were medicine-coated particles injected sans the ability to communicate with nanoparticle advance teams. The major benefit of von Maltzahn's methods is that the medication could be injected anywhere in the body but would only latch onto the cancerous tissue. "If we were injecting this directly into the tumor, it wouldn't be a transformative technology," he says. "It's essential to be able to inject it intravenously anywhere in the body and have it …. home in on the tumor." Once the medicine has been delivered, the nanoparticles would be stripped bare and could safely pass out of the body after being filtered from the blood by the spleen or liver, von Maltzahn says, noting that gold has a very low toxicity profile.

According Catherine Murphy, a chemistry professor at the University of South Carolina in Columbia, the shape of a metal determines how much light it absorbs. "If you want to shine near-infrared light, which is really good for tissue penetration, and burn something up," she says, "a rod shape works really well." Murphy developed the process for transforming spherical bits of gold into the nanorods that von Maltzahn used in his research.

Von Maltzahn, who has worked with his advisor Sangeeta Bhatia, a Harvard-MIT HST electrical engineering and computer science professor, on this research for the past five years, is co-founder of a pair of companies that he hopes will help commercialize his technique: In July 2007, he helped form Salt Lake City, Utah, -based Nanopartz Inc., a worldwide supplier of gold nanoparticles, and in September 2008, he helped create Boston-based Resonance Therapeutics, which will further develop his cancer-fighting techniques. Eugene Zubarev, an assistant chemistry professor at Rice University in Houston, developed the method for mass producing nanoparticles that Nanopartz relies on to make the nanoparticles it sells.

Von Maltzahn two years ago developed another nanotech-based approach to stopping cancer that relied on polymer-coated iron oxide nanoparticles held together by DNA tethers that together help create a visual image of a tumor through magnetic resonance imaging (MRI), as Scientific American.com reported in November, 2007. To test the particles, he and his team implanted mice with a tumor-like gel saturated with nanoparticles and placed those mice into the wells of cup-shaped electrical coils, which activated the nanoparticles via magnetic pulses.

Von Maltzahn says he's currently conducting clinical trials of his near-infrared laser technology (to ablate cancerous tumors), but it is still years away from becoming a routine treatment. The scout-assassin model is even farther from becoming a cancer-fighting staple, says Maltzahn, noting that it could take him and his colleagues another two decades to make it safe and effective enough to use in humans.

Von Maltzahn plans to keep close tabs on his companies but to continue to pursue an academic career as a professor of biomedical or chemical engineering. Neither the business nor the academic aspects of research can be overlooked if medicine is to make its way from the lab to the patient, he says. "One of the things that appeals to me," von Maltzahn says, "is developing therapeutics such as these in a way that they can be commercialized."

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