Using Radio Waves to Bake Tumors

Nanotech News

April 2012

Nanothermal therapy – the use of nanoparticles to cook a tumor to death – is one of the many promising uses of nanotechnology to both improve the effectiveness of cancer therapy and reduce its side effects. Now, a team of investigators from theTexas Center for Cancer Nanomedicine has shown that liver cancer cells will take up targeted gold nanoparticles, absorb radio waves, and generate heat that damages the cells. In addition, the researchers have discovered how to increase the thermal toxicity of these nanoparticles.

This research was led by Steven A. Curley, of the University of Texas M.D. Anderson Cancer Center, and Lon Wilson, of Rice University. The investigators published their results in the journal Nanomedicine.

Biocompatible gold nanoparticles are ideal vehicles for delivering heat to tumors because they are non-toxic, stable, and can be coated with a variety of molecules to target them to tumors. Unlike conventional anticancer agents, gold nanoparticles are harmless unless first activated by an energy source, such as a near-infrared light delivered by a laser. In fact, laser-activated gold nanoparticles are being tested in human clinical trials for the treatment of head and neck cancer. Radio waves, however, have a potential advantage over laser energy because radio waves do not interact with biological tissues and thus can penetrate more deeply within the body than can laser light.

One of the major obstacles to using radiofrequency-activated gold nanoparticles to treat cancer is their tendency to clump together, which reduces their ability to absorb energy and convert it to heat. In the current study, the Texas researchers aimed to develop a precise understanding of why clumping occurs and develop the means to keep it from happening. Their experiments showed that the low pH within endosomes – the tiny vesicles that bring antibody-targeted nanoparticles into cells – is the primary cause of aggregation.

In an attempt to neutralize the acidic pH within endosomes, the investigators treated the cells with one of two different drugs – concanamycin A, an antibiotic not designed for use in humans, and chloroquine, an approved antimalarial agent – that are known to prevent endosome acidification. When the treated cells were exposed to antibody-targeted gold nanoparticles and then radiofrequency activation, heat-triggered cell death increased markedly compared to that seen with cells that were not pre-treated with the acid blockers, by preserving the protein coating on the gold nanoparticle surface. Based on these results, the investigators are now developing antibody-targeted nanoparticles with coatings that will prevent aggregation in the acidic environment of the endosome.

This work, which is detailed in a paper titled, "Stability of antibody-conjugated gold nanoparticles in the endo-lysosomal nanoenvironment: Implications for non-invasive radiofrequency-based cancer therapy," was supported in part by the NCI's Physical Sciences-Oncology Center program, a comprehensive initiative designed to accelerate the application of nanotechnology to the prevention, diagnosis, and treatment of cancer. An abstract of this paper is available at the journal's website.

View abstract

http://nano.cancer.gov/action/news/2012/apr/nanotech_news_2012-4-2c.asp

Contributing toward finding a cure

By MIKE CAPUTO	July 17, 2008

While sitting on the couch watching television at his Garden Town home, Dr. Stephen Freedman envisioned a cure for cancer.

His vision was guided by a television feature, which focused on the progress made by Dr. Steven Curley and John Kanzius, who have made strides toward finding a method to kill cancer cells.

After watching that news feature on an April edition of 60 Minutes, Freedman felt compelled to pick up the phone and call Curley. Freedman was confident that his idea could contribute toward achieving nearly every scientist's dream of finding a cure for cancer. But he still couldn't pick up the phone.

"I figured I'd better wait, might as well wait, he will never get back to me," Freedman said. "I mean he is on 60 Minutes, he is probably being barraged with telephone calls."

So he waited. About a month later, Freedman gathered up the courage to make the call to Curley's office at UT MD Anderson Cancer Center in Houston. A receptionist answered, and promised to pass along Freedman's message. Before he even checked for a return call, Freedman had a message waiting for him at his Adelphi University office less than 24 hours after he phoned Curley.

"It was mind-blowing," Freedman said. "I never expected this."

Freedman, a chemistry professor at Adelphi, told Curley that his extensive work with peptides could possibly enhance the renowned researcher's experiment. Curley, a surgeon and medical researcher, teamed up with Kanzius, a cancer patient and a former radio and television technician, to use radiowaves and nanoparticles to kill cancer cells. Using the heat from radiowaves, Curley and Kanzius' method attaches nanoparticles onto antibodies that make their way to the cancer cells to destroy them.

"I have got to tell you in 20 years of research, this is the most exciting thing I have ever encountered," Curley told 60 Minutes.

Freedman, 59, determined that instead of using antibodies, peptides could be more efficient. That is because if nanoparticles attach to the smaller protein-based peptide, they could have an easier time getting to the cancer cells. According to Freedman, Curley took his idea seriously, and plans to run tests sometime in August.

Making an impact on a potentially groundbreaking study to cure cancer is extra special to Freedman, who lost his 75-year-old father to cancer in 1993.

"It was the worst experience of my life, to see my father waste away with cancer," Freedman said. "This whole experiment has a special meaning."

Freedman has lived in Hewlett since 2005, when he started teaching at area colleges, first at St. John's and now at Adelphi. He spent several years teaching chemistry at Florida Atlantic University in Boca Raton. Freedman, who grew up in Brooklyn, earned his doctorate from Utah State University; a Master's of Science from Polytechnic University; and his Bachelor of Science from Brooklyn College.

It's still early in the experimentation process, and there are still many questions to answer. Though he claims not to be religious, Freedman explained that it is important to have faith for such projects to succeed.

"I request that readers say a prayer for a positive result," he said.

However, he does believe luck will factor in.

"We have so many of the greatest minds working on a cure for cancer, yet there is no cure," Freedman said. "It will take a dramatic stroke of luck to come upon the ultimate answer."

Freedman can be contacted by e-mail at freedman@adelphi.edu.

Comments about this story? Mcaputo@liherald.com or (516) 569-4000 ext. 201.
http://www.usu.edu/ust/pdf/2008/july/itn0717085.pdf

Kanzius’ waves of change (AUDIO & VIDEO)

BY DAVID BRUCE
david.bruce@timesnews.com [more details]

Published: March 09. 2008 6:00AM

Research Assistant Katrina Briggs places a dish containing cancer cells in a laboratory machine at M.D. Anderson Cancer Center in Houston, where progress is being made toward a new cancer treatment thanks to an Erie man’s idea about radio waves. In photo at top, Briggs prepares cancer cells by placing them in a centrifuge. (ROB ENGELHARDT/Erie Times-News)

HOUSTON -- It's Katrina Briggs' job to discover if John Kanzius has found a new way to treat cancer.

Deep in the basement of M.D. Anderson Cancer Center, in a lab not much bigger than a bedroom, Briggs blasts cancer cells with the Millcreek Township inventor's radio-frequency generator.

You can stand right outside the lab and have no idea what is happening. The walls are cinderblock and the only window is covered with black fabric.

"It's the only place where the radio waves won't interfere with other research projects," said Briggs, who has worked for 14 years as a research assistant on different projects. "The floor is 30 feet thick, so nothing vibrates."

Research that has grabbed the attention of 60 Minutes and other national news organizations takes place in a dungeon in Houston, and a similar lab at the University of Pittsburgh Medical Center.


Using radio waves to treat cancer isn't new. Surgeons have burned tumors with radio waves for years.

But targeting individual cancer cells with tiny pieces of metal and burning them with radio waves emitted from outside the body -- that is new, said Steven Curley, M.D., principal investigator for the Kanzius project at M.D. Anderson.

"It's the most exciting thing in which I have ever been involved," said Curley, who has written articles for more than 110 publications in his career.

The wrong floor

AUDIO & VIDEO

Audio: http://www.goerie.com/audio/keating, http://www.goerie.com/audio/houston Video: http://www.goerie.com/video/RFresearch -- Who's Involved John Kanzius came to Erie in 1966 to work as an engineer at WJET-TV and WJET-AM. He stayed there for 35 years, retiring as president and co-owner. Kanzius, 64, now divides his time between homes in Millcreek Township and Sanibel, Fla. He was diagnosed with chronic lymphocytic leukemia in 2002 and continues to be treated for the cancer. He invented his radio-frequency generator in 2003 after growing frustrated with the effects of traditional cancer treatments. "I knew that radio waves could heat metal you had if you stood too close to a (radio) transmitter," Kanzius said. "I thought, maybe it could do the same in cancer cells." Steven Curley, M.D., is a surgical oncologist at M.D. Anderson Cancer Center in Houston, and principal investigator for John Kanzius' radio-frequency generator project. Curley, 51, divides his time between surgery and research. He has written or co-written more than 110 medical and scientific articles and 30 book chapters, mostly dealing with cancer of the gallbladder, bile duct or liver. "Patient care always comes first," Curley said. "But I get a charge out of both surgery and research. Pushing the envelope in research is very stimulating, but if I was just in the lab, with no patient care, I would be lost." Michael Keating, M.D., oversees Kanzius' treatment for leukemia at M.D. Anderson Cancer Center. Keating, no age available, also played an important role in getting Kanzius together with Curley and Smalley in 2005. He treated Kanzius and Smalley, who both were diagnosed with chronic lymphocytic leukemia. Smalley died from the disease in late 2005. Boris Yakobson, Ph.D., is a professor of chemistry, materials science and computational materials science at Rice University, Houston, and an expert on nanoparticles. Yakobson, 53, was a co-writer for Curley's article on Kanzius' invention that was published in October in Cancer, the medical journal of the American Cancer Society. He worked closely with Rick Smalley, Ph.D., a Nobel Prize-winning scientist at Rice who became very interested in Kanzius' project during the last months of his life. Katrina Briggs is a research assistant at M.D. Anderson Cancer Center. She works full time on Kanzius' project. Her duties include growing, harvesting and preparing cancer cells, then subjecting them to Kanzius' radio-frequency generator. She records how they respond to treatment. Briggs, 43, works on the project in three different laboratories. She is part of an eight-member research team.

How did a project that began in Kanzius' winter home in Sanibel, Fla., end up at a world-class cancer institute?

It started when Kanzius, 64, stepped on an elevator and got off on the wrong floor.

Kanzius -- who has chronic lymphocytic leukemia, an incurable type of cancer -- was between physician appointments at M.D. Anderson in 2003 when he stepped into the hospital's main elevator and mistakenly got out on the pediatric floor.

"I saw all these kids, some of them with bald heads and holding IV stands," Kanzius said. "They were going through the same type of thing I was. That's when I knew there needed to be a different way."

Kanzius is not a medical expert. He doesn't even have a bachelor's degree.

But he was a radio engineer before he became a radio and television station president and co-owner. He knew radio waves could heat metal, and that cancer cells are more vulnerable to heat than healthy cells.

So Kanzius went home to Sanibel and began tinkering with pie pans, copper wiring and other materials.

"What if we could get the metal into the cancer cells, then hit them with radio waves?" Kanzius asked. "They would heat the metal, but not the rest of the body."

Heating hot dogs
Kanzius met Curley in 2005. By then he was using his homemade RF generator to quickly heat hot dogs until they burst.


He showed the device to Michael Keating, his leukemia physician at M.D. Anderson.

Keating suggested that Kanzius talk with Curley, who had been using radio waves to kill tumors in some patients. Because Curley had to physically insert needles into tumors to deliver the radio waves, it only worked with certain types of tumors at particular sites.

Curley and Kanzius talked and exchanged e-mails. The surgeon/researcher was intrigued with Kanzius' idea, but said it wasn't much of an improvement over the technique Curley already used.

"I asked John if he could build a device that would do it noninvasively, without using the needles," Curley said. "I thought that would get rid of him. A month later he called and said he had done it. He had called my bluff."

The premise was surprisingly simple: combine nanotubes -- microscopic pieces of gold or carbon that Kanzius had read about -- with antibodies or other agents that target cancer cells, and inject them into a cancer patient.


A patient would then be placed into Kanzius' device, which emits high-powered radio waves. The waves heat the nanotubes and destroy the cancer cells, but leave healthy cells unharmed.

Eureka

(Chris Simund / Erie Times-News)

The key was finding out whether radio waves would heat nanotubes, the tiny pieces of metal that could fit inside a cancer cell.

Curley discussed Kanzius' device with Rick Smalley, Ph.D., a Rice University scientist who had won the Nobel Prize for his work with nanoparticles. Like Kanzius, Smalley had been diagnosed with chronic lymphocytic leukemia and was seriously ill.

"I had an argument with Rick in his hospital room," Curley said. "He looked at me and said it wasn't going to work, but I'll give you some (nanoparticles). It was like, 'Go away son, you're bothering me.'"


Curley took the nanoparticles to the University of Pittsburgh Medical Center in August 2005, where he met Kanzius.

They blasted a small amount of nanoparticles with Kanzius' device and watched in amazement as they quickly heated to about 660 degrees -- more than hot enough to destroy cancer cells.

"It was so hot that the nanoparticles came out of solution," Curley said. "I called Smalley with the news and his answer was, 'Holy ____!'"

It was the "eureka" moment that cancer researchers wait a lifetime to discover, Curley said. Plans were made to test the device at M.D. Anderson and UPMC.

Working in different labs

(Chris Simund / Erie Times-News)

Today, an eight-person research team at M.D. Anderson investigates Kanzius' theory in three different labs.

The basement lab is where researchers blast cancer cells with radio waves and view the results on a state-of-the-art microscope that was paid for by donations from Erie and Sanibel.

They must share space in two upstairs labs with other M.D. Anderson researchers. In those cramped quarters, they grow cells of 20 different types of cancer -- from liver cancer to leukemia -- harvest them and prepare them for Kanzius' device.

"These cells are like baby birds," Briggs said as she placed a deviled-egg tray of leukemia cells into an incubator. "You really have to take care of them. If you don't feed them the right way, they die."


The researchers often work alone, though they are under the supervision of Curley and fellow researcher Paul Cherikuri, Ph.D.

"We adjust our schedules because we often need the same equipment," Briggs said. "The others often are here in the evening."

The pace of progress has been astonishing, Curley said.

They have only been working on Kanzius' devices for a little more than two years, but already have been able to kill cancer cells in human tumors grown in live rabbits without harming the animals.

"There was a fair amount of whooping and hollering in the office that day," Curley said.

Targeting is the key
Now the efforts are focused on targeting, sending nanotubes inside cancer cells and not other, healthy cells.

Curley is reluctant to talk about the progress he and his team are having. He has submitted results to a major medical journal and is under an embargo until it is published.

"I can't jeopardize that," Curley said. "A colleague of mine at another institution talked about his project with a local television station and the journal sent back his paper without publishing it. It put their project way behind. We can't afford that."

But asked how the work is going overall, Curley said there have been "no major glitches" and that "I fully believe this will get to human trials."

Fatigue faded away
But human trials are years away and work continues at M.D. Anderson.

Kanzius was in Houston in late February to see Keating, his leukemia doctor. He wasn't feeling particularly good.

Chemotherapy and a recent viral infection had stolen 10 pounds from his already slender frame.


He barely slept the previous night, then took an early morning flight from Sanibel to M.D. Anderson.

"It's the last time I do that," Kanzius said.

Kanzius then underwent bone-marrow aspiration -- a painful procedure where doctors stick a long needle into his pelvis, and remove blood and small pieces of bone. It was done to see how Kanzius responded to chemotherapy.

Instead of grabbing some sleep, Kanzius and his wife, Marianne, rode an elevator to the hospital's basement to see the devices -- his devices.

As a television crew filmed footage for an upcoming story on 60 Minutes, Kanzius slipped on a pair of reading glasses and examined one of his devices with Curley.


The fatigue faded away, at least for the moment, as Kanzius fiddled with dials and peppered Curley and Briggs with questions about how the device had been operating.

He then watched video of cancer cells rupturing when treated with his device.

"I find it humbling, that this institute and Dr. Curley have endorsed this program, and find it amazing what they have accomplished in such a short time," Kanzius said. "Just watching the cell cultures here today, I just get goose bumps from watching it. I can't see it enough times. Every time it excites me."

DAVID BRUCE can be reached at 870-1736 or by e-mail.

A look at how nanotubes may work in cancer fight
HOUSTON -- A 3-foot mesh cylinder sat in a corner of Boris Yakobson's untidy office at Rice University.

"Aha!" said Yakobson, 53, a professor of chemistry and materials science at Rice. "That is a model of a nanotube. Of course, the real ones are much, much smaller."

Yakobson studies nanotubes at Rice and has written research papers about them. Nanotubes play a vital role in John Kanzius' experimental method of treating cancer.

These tiny pieces of carbon or gold, so small that tens of thousands of them can fit across a human hair, are placed inside cancer cells, then heated by Kanzius' radio-frequency generator.

The heat destroys cells with nanotubes, while cells without them are unaffected.

"This is just one use for nanotubes," Yakobson said. "Carbon nanotubes are among the hardest substances we know, so the possibilities are many."

Nanotubes, first discovered in Japan in 1991, are hex-agonally shaped arrangements of carbon or gold formed into tubes.

They used to be expensive to manufacture, about $1,000 per gram, but new technology has cut the cost to about $10 a gram, depending on the type.

"There is a lot of work going on right now with nanotubes. It's very exciting," Yakobson said.

"The medical applications are interesting. I am looking forward to seeing how (principal investigator for the Kanzius project) Steve Curley does with them."

Concept receives media attention
HOUSTON -- One of John Kanzius' grandchildren was visiting a doctor in February, when she spotted him on a waiting-room television.

CNN was broadcasting a story about Kanzius' radio-frequency generator.

The cable network originally showed the feature in 2007, but reran it on a health show it sends to physician offices across the country.

"She told people, 'That's my grandpa on TV,'" Kanzius said with a chuckle.

You can expect to see more of Kanzius on national television in upcoming weeks.

"60 Minutes" has interviewed Kanzius and researchers at M.D. Anderson Cancer Center in Houston for a story it plans to broadcast about his invention. A date has not been announced, but Kanzius said he thinks it will run in late March.

Having Kanzius' invention broadcast on national television could boost fundraising efforts, but it also causes principal investigator Steven Curley, M.D., to worry about potential problems.

"It scares the heck out of me," Curley said with a thin smile.

"I told ("60 Minutes" reporter) Leslie Stahl that we're not ready to treat patients, but viewers might not hear that. I also don't know what John said about things."

It's not the first time a national television news show or large-circulation newspaper has reported on the Kanzius project.

Stories have run on the CBS "Early Show", "Good Morning America" and in the Los Angeles Times.

DAVID BRUCE can be reached at 870-1736 or by e-mail.

New Fundraising Organization
A new nonprofit organization is raising money for John Kanzius' radiofrequency generator.

Community united for a Cancer Cure has become the John Kanzius Cancer Research Foundation. The name has changed because the foundation is now a stand-alone nonprofit organization.

The foundation raises money and awareness for Kanzius' project. The money goes for research at M.D. Anderson Cancer Center and the University of Pittsburgh Medical Center.

The foundation and its predecessor, the CCC, have raised $500,000. Some of the money has been used to buy a state-of-the-art microscope at M.D. Anderson.

To donate, visit
www.johnkanziuscancerresearchfoundation.org or visit any First National Bank location.

http://www.goerie.com/apps/pbcs.dll/article?AID=/20080309/NEWS02/803090417/-1/NEWS

Cure for cancer? Sanibel man may be on to something

Cancer patient came up with treatment while sick

By JENNIFER BOOTH REED • jreed@news-press.com • March 3, 2008

In a laboratory at M.D. Anderson Cancer Center in Texas, researchers injected nanoparticles into tumors they had grown in rabbits. They placed the animals on a special machine that would direct radio waves at the tumor site. They flipped a switch.

The waves heated the nanoparticles and bang! Within seconds, the nanoparticles released enough heat to kill the cancer cells. No drugs, no radiation, no surgery, no apparent side effects and the healthy tissue surrounding the tumor remained unscathed.

In a laboratory at the University of Pittsburgh, another research team tried a similar experiment, this time on rats. It, too, was a success.

Imagine the implications for humans.

It looks like John Kanzius was right.

The part-time Sanibel resident dreamed up the radio wave therapy four-plus years ago, sick from chemotherapy himself and saddened by a glimpse of children receiving the drugs at the hospital where he underwent treatment.

Now, the research is emerging to back his theory.

Kanzius was diagnosed with leukemia in 2002. As he went through those initial rounds of chemotherapy, he told himself there had to be a better way.

Kanzius, 64, is a former radio and television station owner from Pennsylvania with no medical background but, clearly, an uncanny mind for figuring things out.Sick and sleepless, Kanzius built his prototype at his Sanibel home in eight weeks during the fall of 2003. It’s still in his garage.

His first experiments had been on hot dogs injected with copper sulfate. Could he, he wondered, “transmit” the radio frequency directly to the afflicted areas?

Radio waves have been used before in a cancer treatment known as ablation. Doctors insert needles into a tumor and deliver radio waves to the site. The energy heats and destroys the malignant tissue. But the technique can damage healthy tissue, not to mention force the patient to endure the invasive insertions.

Kanzius’ model solves both problems.

Dr. Steven Curley of M.D. Anderson published his team’s results in the December 2007 issue of the journal Cancer. Dr. David Geller at the University of Pittsburgh presented his team’s research abstract two weeks ago at the annual Academic Surgical Congress in Huntington Beach, Calif.

“It is far enough along that we’re talking about human trials,” Kanzius said on a recent afternoon.

Kanzius and Curley will give a public talk Tuesday at South Fort Myers High School where they’ll recount the tale of this businessman-turned-patient-turned-inventor-turned-researcher, tell the community about ongoing research and outline what’s next in turning Kanzius’ idea into medical reality.

“It’s a pretty remarkable story,” said Curley from his lab in Texas. “In 20 years, I’ve never run into somebody who had something that I thought was viable.”

“In the last year we’ve made excellent progress,” Geller said.

The doctors are heartened.

So is Kanzius.

“If you got the treatment, you wouldn’t even know it,” he said.

Promising as it is, the research is just beginning.

“Does it just stun the cancer or does it disappear?” asked Geller, posing one of many questions his team must answer.

Other questions: Will the machine need to be adapted for larger animals and then for humans? Will there be different strategies to treat different kinds of cancer? And, how can doctors get the nanoparticles to seek out and latch onto only the cancer cells? So far, they have injected the particles directly into tumors, which is of limited value if a cancer has spread.

In Texas, Curley ticked off another list of questions: What’s the best kind of nanoparticle to use and in what dose? How should the nanoparticle be shaped and do some shapes conduct heat better than others? Are the nanoparticles nontoxic, as they appear to be? Only longer-term toxicity studies will tell.

He continued: Is the therapy better suited for some kinds of cancer over others? Should any drugs be taken along with the radio wave therapy to increase its effectiveness?

He’s encouraged by the early success.

“The heating was unbelievable,” Curley said. “We’re literally thinking in terms where this lasts no more than 30 to 60 seconds.”

Six months before his diagnosis, Kanzius had intended to retire.

Cancer — both his ongoing treatment and his search for an alternative — has become a full-time job.

His story by now has been played out in media ranging from local outfits in Lee County and hometown Erie, Pa., to The Los Angeles Times to Readers Digest to the Pittsburgh Post-Gazette. You can watch a video of a television interview replay on MySpaceTV. The posted description begins “This guy rocks.”

In his spare time, Kanzius works on an equally promising find in alternative fuel development. He discovered that salt water will burn when it’s subjected to the radio field his machine casts and lit with a match. But that’s a story for another day.

Kanzius doesn’t want to be known as the guy who cured cancer.

“I just want to be the guy that comes up with the idea and is working with the researchers,” he said.

Last week he went to M.D. Anderson for another round of tests for his own cancer and to see the progress Curley had made.

“It’s just phenomenal,” Kanzius said.

He wants to offer encouragement — that’s why he holds public talks — but doesn’t want to give false hope.

His cancer appears to be at bay. Preliminary results suggest his last round of treatment was effective. And Curley’s research is speeding at rates uncommon in the medical world.

“Nobody could have ever thought this was possible,” Kanzius said.

http://www.news-press.com/apps/pbcs.dll/article?AID=/20080303/HEALTH/80302048/1075