Showing posts with label plaque. Show all posts
Showing posts with label plaque. Show all posts

Tuesday, July 29, 2008

New disease-fighting nanoparticles look like miniature pastries

July 29, 2008
By Gwen Ericson

-- Ultra-miniature bialy-shaped particles — called nanobialys because they resemble tiny versions of the flat, onion-topped rolls popular in New York City — could soon be carrying medicinal compounds through patients' bloodstreams to tumors or atherosclerotic plaques.

The nanobialys are an important addition to the stock of diagnostic and disease-fighting nanoparticles developed by researchers in the Consortium for Translational Research in Advanced Imaging and Nanomedicine (C-TRAIN) at Washington University School of Medicine in St. Louis. C-TRAIN's "smart" nanoparticles can deliver drugs and imaging agents directly to the site of tumors and plaques.

The new nanobialys weren't cooked up for their appealing shape — that's a natural result of the manufacturing process. The nanobialys answered a need for an alternative to the research group's gadolinium-containing nanoparticles, which were created for their high visibility in magnetic resonance imaging (MRI) scans.

Gadolinium is a common contrast agent for MRI scans, but recent studies have shown that it can be harmful to some patients with severe kidney disease.

"The nanobialys contain manganese instead of gadolinium," says first author Dipanjan Pan, Ph.D., research instructor in medicine in the Cardiovascular Division. "Manganese is an element found naturally in the body. In addition, the manganese in the nanobialys is tied up so it stays with the particles, making them very safe."

The bulk of a nanobialy is a synthetic polymer that can accept a variety of medical, imaging or targeting components. In the July 2008 issue of the Journal of the American Chemical Society the researchers report that targeted manganese-carrying nanobialys readily attached themselves to fibrin molecules, which are found in atherosclerotic plaques and blood clots. Laboratory-made clots then glowed brightly in MRI scans. They also showed that the nanobialys could carry both water-soluble and insoluble drugs.

Pan, who is a research instructor in medicine, played a leading role in the creation of nanobialys and chose the particles' name. "When we looked at the particles with an electron microscope, we saw they are round and flat, with a dimple in the center, like red blood cells, but also a little irregular, like bagels," he says. "I came across the word bialy, which is a Polish roll like a bagel without a hole that can be made with different toppings. So I called the particles nanobialys."

Pan is one of a group of researchers headed by Gregory M. Lanza, M.D., Ph.D., and Samuel A. Wickline, M.D. Lanza is an associate professor of medicine and biomedical engineering. Wickline is a professor of medicine, physics, biomedical engineering and cell biology and physiology. Lanza and Wickline are Washington University cardiologists at Barnes-Jewish Hospital.

Nanoparticles can be a more effective way to administer medications and imaging contrast agents because they are targeted, packaged units — drugs and imaging agents stay on the nanoparticles, which can be made to concentrate at a specific site in the body.

In animal studies, the research group has shown that their original, spherical nanoparticles can carry therapeutic compounds to tumors and atherosclerotic plaques. These nanoparticles also can hold thousands of molecules of gadolinium, which allows the researchers to use standard MRI scanning equipment to see where the nanoparticles congregate. The scans can then detect the size of lesions as well as the effect of drugs delivered by the nanoparticles.

But gadolinium has recently been linked to nephrogenic systemic fibrosis (NSF). First described in 2000, NSF is an unusual progressive, incurable disease seen in about 3 percent of patients with severe kidney disease who have had MRI scans using gadolinium. In NSF, collagen accumulates in tissues causing skin hardening and thickening, joint stiffening that can lead to physical disability, and disorders of the liver, lungs, muscles and heart.

"Even though it seems that gadolinium affects only those with severe renal failure, physicians have decided not to use gadolinium even in those with moderate renal failure," Lanza says. "A lot of patients with diabetes or hypertension develop renal failure, so that decision potentially affects many people. Our goal has always been that our nanoparticle technology should be able to help everyone. And with a growing number of people having diabetes and related cardiovascular problems, we knew we needed to find a substitute for gadolinium-based particles — nanobialys are our first step in that direction."

The researchers will continue to adapt the nanobialys for a variety of medicinal applications and work to develop other types of nanoparticles so that they can supply a wide range of medical needs.

"We're not sitting in the lab generating nanoparticles and then looking for what they could be used for," Lanza says. "We see a medical problem and ask what kind of particle might overcome it and then try to create it."


Pan D, Caruthers SD, Hu G, Senpan A, Scott MJ, Gaffney PJ, Wickline SA, Lanza GM. Ligand-directed nanobialys as theranostic agent for drug delivery and manganese-based magnetic resonance imaging of vascular targets. Journal of the American Chemical Society 2008 Jul 23;130(29):9186-7.

Source

Saturday, June 21, 2008

Can this man cure cancer? And viral infection? And arterial plaques?

By MATT CLARK (Contact)

Video

He’d been diagnosed with a rare form of B-cell leukemia in 2002, and he’d endured months of chemotherapy.

But still the cancer persisted. As he tells it: “I go into a partial remission or whatever. In another six or eight months, it’s back again. So, I go back into some more chemotherapy.”

Then one late night in 2003, unable to sleep and energized with an idea, the chemo-battered Kanzius began to tear apart the couple’s vacation home on Sanibel Island.

“Of course, I couldn’t say at that point that I’m working on a cancer treatment.” The 64-year-old Kanzius (it’s pronounced like the state) remembers thinking about the parts he’d need. And how he’d explain all this to his wife, Marianne.

“She would have found the nearest psychiatrist and said, ‘After chemotherapy tomorrow, I’ve got another appointment for you,’” he says. “So she would say, ‘What are you doing?’ And I would just tell her that I was working on some stuff for amateur radio.”

Kanzius’ goal was to focus a large number of low-frequency radio waves into a small area. The idea was to heat metal, and in turn kill cancer cells. The same thing that happens when metal is placed in a microwave oven, which uses frequencies a million times more powerful to vibrate molecules and generate heat. The metal heats up. Way up.

Get the metal into cancer cells, Kanzius reasoned, and the cells would be destroyed without harming healthy cells in the body.

He has no medical background, not even a college degree. Still, Kanzius was determined to develop a new cancer treatment, and he used his background in electronics — specifically radio frequency transmitters — to move forward.

At 22, Kanzius worked at RCA as a technical assistant. He remembers the time when the company couldn’t solve a problem with its color television transmitters, which had put RCA at odds with Federal Communications Commission specifications and some of its customers.

“I was able to do in one day what they couldn’t do in two years with all of their Ph.D.’s, and it got me well-recognized,” Kanzius says proudly. “I was able to fix that with a 50-cent part, in like an hour.

Later, Kanzius co-owned and operated a broadcasting company in Erie, Pa., where he still lives part of the year. And he still puttered at home with his radios.

Back in Erie, Kanzius had all the requisite parts. But on the island, he had to get creative. The key ingredient turned out to be heavy-duty pie plates he found rummaging in the kitchen. His wife of 44 years would later search out the radio parts he needed.

“John is often up in the middle of the night,” she says of the early morning her husband was pulling out pie plates. “That night, he was like a man possessed. He was making an awful lot of noise and racket.

“I asked him to go back to sleep and he said, ‘I have to think about this, I can’t sleep.’ He had chemotherapy in the morning, so I was concerned.”

That second round of chemo had made Kanzius so weak he was even unable to board a plane for the funeral of his mother, who died at 83 of lung cancer in late 2003.

But he pressed on.

Soon, Kanzius’ makeshift laboratory in the garage of his Sanibel Island home took shape. Soon, he’d be injecting pieces of metal into hot dogs and liver. The machine’s waves successful heated the metal embeded in the meat. The idea of a new cancer-fighting treatment was coming together.

Soon after Kanzius acquired patents for his work, the machine was featured in a newspaper article in the Erie Times-News. That got the attention of Dr. David Geller, then co-director of the Liver Cancer Center at the University of Pittsburgh Medical Center. Geller says he was skeptical at first.

Then Dr. Steven Curley got on board. Curley is a professor of surgical oncology at M.D. Anderson Cancer Center in Houston, rated No. 1 in cancer treatment by U.S. News and World Report for four of the past six years.

Curley already had been working with radio frequency treatment methods for cancer, and was part of the effort that led to U.S. Food and Drug Administration approval for radio frequency ablation, a treatment that works by using a needle-like probe into — or next to — a cancerous tumor. Radio energy from the needle kills the cancer cells — but sometimes can harm surrounding tissue.

Radio frequency ablation has not been effective on more difficult-to-reach tumors, nor does it have an effect on a cancer that has metastasized, or spread to other parts of the body. And Curley’s method, one of four similar ways of using superheated probes on cancer cells, still required a device to be inserted, and then heated.

The key ingredient in the Kanzius innovation are nanoparticles — pieces of metal so small that 75,000 to 100,000 of them can fit across the tip of a human hair. They are introduced into the body where the cancer lives, and then the machine ignites them to cell-killing temperatures.

For the very first experiments, Kanzius and Curley went to Nobel laureate Rick Smalley for the nanoparticles. Smalley was skeptical that the process would work, but became a believer after the nanoparticles successfully burned when activated by the machine. And on his deathbed in October of 2005, Smalley reportedly asked Curley to promise the research would continue.

And it has.

Every experiment by researchers has led them closer to clinical trials in humans, which the researchers believe could occur in three to five years. Early experiments have demonstrated that cancer cells paired with nanoparticles can be destroyed, while leaving nearby healthy cells intact.

In an important experiment performed by Curley, pancreatic cancer cells and liver cancer cells were combined with nanoparticles in petri dishes, and then exposed to the radio frequency waves created by Kanzius’ machine. The successful results were presented in January of 2007 at a conference of the American Society of Clinical Oncology.

Then the researchers tested the theory on animals: Both Curley and Geller have reported success in destroying cancerous tumors in lab animals — using Kanzius’ machine and nanoparticles.

Curley’s success with tumors in rabbits was published in October of last year in Cancer, a medical oncology journal published by the American Cancer Society. Geller’s success treating cancerous cells in rats is expected to be published in August.

All are hopeful signs. But these breakthroughs have only worked on tumors, not cancer that has spread throughout the body.

The next step is to get the nanoparticles to hitch a ride on the body’s disease-fighting antibody cells right to the cancer, no matter where it is hiding. Patients would take a pill, or be injected with a nanoparticle-antibody cocktail. The microscopic metallic particles could then be zapped by Kanzius’ harmless radio field. The waves would kill the cancer cells in seconds — or at least that’s the hope.

“In this whole process, that’s considered the holy grail,” Kanzius says. “To go after the specific metastasized cells.”

Geller explains it this way: “Lung, breast, colon and prostate — none of those patients die of their primary (cancer), they die from metastasis.”

But before anyone gets too excited, Kanzius offers this caveat: If the research leads to treatment in humans, it won’t necessarily mean cancer is cured. Kanzius says that many types of cancer, after being destroyed, can regenerate. Which may mean that some patients will have to get retreated at regular intervals.

Kanzius remembers the call he received from Curley when his experiments first showed that cancerous tumors could be destroyed in laboratory animals. That was around Christmas of 2006, he says.

“That was a big day for him and he called me right after he got the results,” Kanzius says. “I was very excited, you know. I told my wife, ‘This is unbelievable. It works.’”

Both Kanzius’ machine and the researchers’ targeting mixtures will enter the FDA approval process at the same time — probably within months. And it probably won’t be difficult to find willing candidates for clinical trials, Kanzius included. But will they occur before cancer takes his life?

Medical communities are starting to warm to the possibilities. Lee Memorial Health System, for example, has signed up to host clinical trials. Dr. Sharon MacDonald, chief officer of the Lee Memorial Health System Foundation and vice president of oncology, calls the targeting treatment “very promising.”

She says that unlike the current limited stock of cancer treatments, Kanzius’ machine wouldn’t require having toxic chemicals, radiation or medical instruments enter the body. She says the new treatment will use non-toxic gold nanoparticles and proven, lab-created antibodies to target the cancer cells.

MacDonald says taking part in early clinical trials will be a good fit for Lee Memorial’s new cancer center being constructed near the intersection of Interstate 75 and Colonial Boulevard in Fort Myers.

“It piqued our interest to be able to be local and be only one of a handful of sites in the nation to be able to participate in a human trial when it comes about,” MacDonald says.

Kanzius, who headed back north to Erie in early May, says he hopes to build a larger version of his machine by August. He says it will allow a person to receive treatment throughout his or her body.

He says his machine is also showing promise in the treatment of like HIV, and could play a role in overcoming future water shortages. For example, if it can remove salt from sea water, the world might have an almost limitless supply of drinking water. Kanzius initially experimented with test tubes full of seawater collected from the canal behind his Florida home, and now research on the theory is progressing at Penn State University.

The possibilities about what the machine might accomplish run rampant. Can it defeat viruses and infections? Heart disease? No research has begun on those hopeful thoughts, but Kanzius has submitted patents for the treatment of other diseases. “One of those viruses could be HIV,” Kanzius says. “The viruses are actually easier to work with than cancer cells,”

Kanzius also says it may be possible to target plaques in arteries.

“It’s exciting knowing that there are other uses out there,” Kanzius says.

But making money isn’t the motivation. Kanzius says he filed numerous patents to protect the machine and the research surrounding it. There will be plenty of money to be made in creating the nanoparticle-antibody cocktails, he says.

But just getting to the finish line is going to be difficult. “The major setback is that the research is very expensive and most of the research that I’ve been doing is because of philanthropic funding,” says researcher Geller.

No big company has stepped in to fund research into Kanzius’ machine, so the money has to come from somewhere else. He’s established the John Kanzius Cancer Research Foundation. Its Web site — www.kanziuscancerresearch.com — has drawn a rash of donations as media reports on the device have spread.

Kanzius is not letting all of this attention go to his head. Being interviewed on “60 Minutes” by Lesley Stahl. Going on the “The Early Show.” Reporters asking for interviews, from around the world.

Most of the media requests go unanswered. His time, he says, is limited.

“I’d be better off building better equipment, concentrating on ways to improve it, than figuring out what flight I’m going to take to be on Oprah Winfrey,” he says.

Even his Sanibel neighbors are interested, and supportive.

During a late April interview for this story, Sanibel resident Candy Scothorn can’t help but interrupt. “Congratulations,” she tells Kanzius. “We’re just very thrilled that you’re here and we’re proud. We greatly appreciate it.”

Scothorn reaches out her hand to be shaken.

“I do it this way,” he tells her, bumping knuckles instead of grasping her hand. It’s one way Kanzius lowers his exposure to germs that might attack his weakened immune system.

“It’s fabulous that he’s a human being. A soul,” adds the 51-year-old Scothorn.

Wife Marianne says it’s her husband’s cancer that keeps him from getting too excited.

“It has humbled both of us, and it’s kept us very grounded. His passion has been working on this project. That has taken most of his energy. How he does it, I don’t know, because I get tired.”

And yet Kanzius keeps going. Waiting for results. Battling cancer. Hanging on.

“‘Til I see it work, you know, (until) I see the first human treated and it works,” he says, “then it will be a day to celebrate and break open the champagne. There’s no need to build yourself up ‘til it gets to where you really want it to.

“There is probably going to be a stem cell transplant eventually,” he says about his own prospects against an unrelenting disease. ”But I’d rather do this than any other. At least I know this will work.”

Source

I note that Kanzius envisions using his radio wave machine to zap viruses, bacteria, and arterial plaque with an appropriately accompanying metal nanoparticle such as gold attached to them. It seems to me that regarding viruses, should NanoViricides include a metal nanoparticle in their virus seeking and attaching micelle-ligand Cide they would have a double barreled attack - 1) From the Cide itself, and 2) From the radiowave heating-destruction involving the metal nanoparticle.

And it must be noted that Kanzius' biggest remaining problem is getting the metal nanoparticle to go to - be attracted to - the virus and attaching itself to the virus - and we HAVE THAT BIT SOLVED ALREADY for our Cide!
*
*

Monday, March 24, 2008

Air pollution may cause heart disease

Patients prone to heart disease may one day be told by physicians to avoid not only fatty foods and smoking but air pollution too.

A new academic study led by UCLA researchers has revealed that the smallest particles from vehicle emissions may be the most damaging components of air pollution in triggering plaque buildup in the arteries, which can lead to heart attack and stroke. The findings appear in the Jan. 17 online edition of the journal Circulation Research.

The scientists identified a way in which pollutant particles may promote hardening of the arteries — by inactivating the protective qualities of high density lipoprotein (HDL) cholesterol, known as "good" cholesterol.

A multicampus team from UCLA, the University of Southern California, the University of California, Irvine, and Michigan State University contributed to the research, which was led by Dr. Andre Nel, UCLA's chief of nanomedicine. The study was primarily funded by the National Institute of Environmental Health Sciences and the U.S. Environmental Protection Agency (EPA).

"It appears that the smallest air pollutant particles, which are the most abundant in an urban environment, are the most toxic," said first author Dr. Jesus Araujo, assistant professor of medicine and director of environmental cardiology at the David Geffen School of Medicine at UCLA. "This is the first study that demonstrates the ability of nano-sized air pollutants to promote atherosclerosis in an animal model."

Nanoparticles are the size of a virus or molecule — less than 0.18 micrometers, or about one-thousandth the size of a human hair. The EPA currently regulates fine particles, which are the next size up, at 2.5 micrometers, but doesn't monitor particles in the nano or ultrafine range. These particles are too small to capture in a filter, so new technology must be developed to track their contribution to adverse health effects.

"We hope our findings offer insight into the impact of nano-sized air pollutant particles and help explore ways for stricter air quality regulatory guidelines," said Nel, principal investigator and a researcher at UCLA's California NanoSystems Institute.

Nel added that the consequences of air pollution on cardiovascular health may be similar to the hazards of secondhand smoke.

Pollution particles emitted by vehicles and other combustion sources contain a high concentration of organic chemicals that could be released deep into the lungs or even spill over into the systemic circulation.

The UCLA research team previously reported that diesel exhaust particles interact with artery-clogging fats in low-density lipoprotein (LDL) cholesterol to activate genes that cause the blood-vessel inflammation that can lead to heart disease.

In the current study, researchers exposed mice with high cholesterol to one of two sizes of air pollutant particles from downtown Los Angeles freeway emissions and compared them with mice that received filtered air that contained very few particles.

The study, conducted over a five-week period, required a complex exposure design that was developed by teams led by Dr. Michael Kleinman, professor of community and environmental medicine at UC Irvine, and Dr. Constantinos Sioutas, professor of civil and environmental engineering at USC.

Researchers found that mice exposed to ultrafine particles exhibited 55 percent greater atherosclerotic-plaque development than animals breathing filtered air and 25 percent greater plaque development than mice exposed to fine-sized particles.

"This suggests that ultrafine particles are the more toxic air pollutants in promoting events leading to cardiovascular disease," Araujo said.

Pollutant particles are coated in chemicals sensitive to free radicals, which cause the cell and tissue damage known as oxidation. Oxidation leads to the inflammation that causes clogged arteries. Samples from polluted air revealed that ultrafine particles have a larger concentration of these chemicals and a larger surface area where these chemicals thrive, compared with larger particles, Sioutas noted.

"Ultrafine particles may deliver a much higher effective dose of injurious components, compared with larger pollutant particles," Nel said.

Scientists also identified a key mechanism behind how these air pollutants are able to affect the atherosclerotic process. Using a test developed by Dr. Mohamad Navab, study co-author and a UCLA professor of medicine, researchers found that exposure to air pollutant particles reduced the anti-inflammatory protective properties of HDL cholesterol.

"HDL normally helps reduce the vascular inflammation that is part of the atherosclerotic process," said Dr. Jake Lusis, study co-author and a UCLA professor of cardiology, human genetics and microbiology, immunology and molecular genetics. "Surprisingly, we found that exposure to air pollutant particles, and especially the ultrafine size, significantly decreased the positive effects of HDL."

To explore if air particle exposure caused oxidative stress throughout the body — which is an early process triggering the inflammation that causes clogged arteries — researchers checked for an increase in genes that would have been activated to combat this inflammatory progression.

"We found greater levels of gene activation in mice exposed to ultrafine particles, compared to the other groups," Lusis said. "Our next step will be to develop a biomarker that could enable physicians to assess the degree of cardiovascular damage caused by air pollutants or measure the level of risk encountered by an exposed person."

Researchers added that previous studies assessing the cardiovascular impact of air pollution have taken place over longer periods of exposure time, such as five to six months. The current study demonstrated that ill effects can occur more quickly, in just five weeks.

"Further study will pinpoint critical chemical and toxic properties of ultrafine particles that may affect humans," Nel said.

The research team included investigators from the fields of nanomedicine, cardiology and genetics. Additional co-authors included Berenice Barajas, Xuping Wang, Brian J. Bennett and Ke Wei Gong of the David Geffen School of Medicine at UCLA, and Jack Harkema from the department of pathobiology and diagnostic investigation at Michigan State University.

Additional grant support was provided by the National Institute of Allergy and Infectious Diseases; the National Heart, Lung and Blood Institute; and the Robert Wood Johnson Foundation.

Link