Nanoparticles to Fight Cancer from the Inside

[abdulhakeem]

03.09.2003

Scientists at Berlin's Charité Hospital have developed a new technique using nanotechnology to fight cancer cells. Tiny iron oxide particles are used to give malignant cells a high "fever" they can't survive.

The iron oxide particles that could soon prove formidable solders in the battle against cancer don't look threatening at all. In fact, they're invisible to the human eye and even to all but the most powerful microscopes. But the size of these nanoparticles, with diameters about 10,000 times smaller than that of a human hair, turns out to be their advantage since they can easily penetrate cancer cells and wreak significant damage once inside.

It might be called a Trojan horse strategy that scientists at Berlin's Charité Hospital have developed to fight a particularly aggressive form of brain cancer called glioblastoma, but which could be used to treat other forms of the disease.

The new procedure involves coating the tiny iron oxide particles with an organic substance, such as the sugar glucose, and injecting them into a malignant tumor. The tumor, which has a fast metabolism and correspondingly high energy needs, greedily sucks up the little particles masquerading as sugar pellets of a sort. Healthy cells, on the other hand, show little interest. The voraciousness of cancer cells proves to be the tumor's downfall.

Scientists then use a magnetic field to heat up the nanoparticles that have ensconced themselves in the malignant tissue to temperatures up to 45 degrees Celsius (113 degrees Fahrenheit). It has the effect of giving the cells a fever that they can't endure, since while cancer cells are ferocious, scientists have long known that heat is their Achilles' heel.

The heat destroys many of the cancer cells in and around the tumor or weakens them to a point that they are more effectively treated with radiation or chemotherapy.

The treatment, known as magnetic fluid hyperthermia, has been successfully used in extending the lives of laboratory rats which were implanted with malignant brain tumors. The rats receiving the nanotherapy lived four times as long as rats receiving no treatment.

Human trials

Now the hospital reports it will try the new technique on 15 patients who are suffering from Glioblastoma mutiforme, the most common primary brain tumor and the most aggressive form of brain cancer. The life expectancy prognosis in human patients according to statistics is on average 6 months to one year.

"We expect the new method to extend the life expectancy of glioblastoma patients, Klaus Maier-Hauff, director of the project and head of neurosurgery at the teaching hospital of the Charité, told reporters.

The treatment is particularly attractive to doctors working with tumors in the brain since the nanoparticles are placed in the malignant tissue by means of an extremely precise electronic navigation system. That means they can reach tumors that lie outside the reach of conventional surgical treatment, such as those situated deep in the brain or in regions that are responsible for essential tasks like speech or motor functions.

Breast cancer

But the heat therapy is theoretically not limited to types of brain cancer. Scientists who work with breast cancer are preparing to adopt the therapy for their own patients.

"I won't have to remove the breast if I can also work in a non-invasive way," Ingrid Hilger of the Institute for Diagnostic and Intervention Radiology at the University of Jena told the newsmagazine Der Spiegel.

She hopes that the treatment will be especially effective with breast cancer patients, since breast tumors do not lie in the immediate vicinity of essential organs. Therefore it would be possible to use higher temperatures when heating the malignant tissue.

"Ideally that means we could dispense with parallel treatments with radiation and chemotherapy," she said.

Some scientists warn against too much euphoria, saying the iron oxide nanoparticles used in the treatment could do later damage to other tissues of the body if they reached the bloodstream. But scientists working on the project say as long as the amount of metal injected into the body stays under a certain level, the danger of "nanopoisoning" is relatively low.

http://www.dw-world.de/dw/article/0,,961880,00.html

[abdulhakeem]

Non-invasive Methods to Treat Cancer Through Nanotechnology

Over the past three decades since the beginning of the National Cancer Initiative in 1971, there have been major advances in the diagnosis and treatment of cancer. However, the ravages of cancer continue to be a major healthcare concern of our society and nation. As Dr. Eschenbach, Director of the National Cancer Institute stated in September 2004, “… in spite of those opportunities and those breakthroughs, the painful reality is that as we sit here today, one American every minute continues to die from this disease. It remains the disease that Americans fear most because of the suffering and devastation as well as death it brings, and we know that one out of every two men, and one out of every three women in their lifetime will be told they have cancer.” Current treatments by radiation and chemotherapy are also extremely invasive with excruciating side effects. Nanotechnology promises new methods for noninvasive treatment of cancer with minimal side effects. One of the promising approaches is by targeted destruction of cancerous cells using localized heating.

The destruction of tumors by locally heating tissue sufficient to cause its demise has been under investigation for some time. The benefits of thermal therapeutics over conventional removal by surgery are numerous; most thermal approaches are minimally or non-invasive, relatively simple to perform, and have the potential of treating tumors embedded in vital regions where surgical removal is not feasible. Ideally, the activating energy to heat the tumor would be targeted on the embedded tumor with minimal effect on surrounding healthy tissue. Unfortunately, conventional heating techniques such as focused ultrasound, microwaves, and laser light do not discriminate between tumors and surrounding healthy tissue. Thus success has been modest and typically results in some damage to surrounding tissue. Recent work around the world suggests that nanostructures designed to attach to cancerous cells may provide a very powerful means for highly localized energy absorption at the sites of cancerous cells.

Researchers at Rice University in the USA recently reported work on mice in which gold-coated nanoparticles treated to attach to cancerous cells were heated using infrared radiation. Sources of infrared radiation, in a manner analogous to radio stations, can be tuned to transmit at a narrow band of electromagnetic frequencies. Additionally, dimensions of the “nanoshells” can be changed to absorb a particular infrared radiation frequency. Researchers can thereby choose a frequency of the infrared radiation that couples with the gold coated nanoparticles, and at the same time does not couple to the tissue of the body, enabling selective destruction of cancerous cells and tumors[1].

The results of a carefully controlled experimental trial with mice, while preliminary, were very encouraging. Mice into which cancerous cells were introduced and were treated with the nanoshells-infrared radiation therapy appeared healthy and tumor free more than 90 days later; all those receiving the same introduction of cancerous cells and not treated had their cancers grow to such an extent that they were euthanized after an average of 12 days.

In Europe, work at Charité Hospital in Berlin[2], coupled with scientists at the Friedrich-Schiller-Universität Jena, have shown that magnetic nanoparticles interstitially injected directly into the tumor - heated with radio-frequency radiation[3] – can destroy cancer cells in a human brain tumor and is also believed to enhance the effects of subsequent radiation therapy. The nanoparticles localize on the tumor due to a special biomolecularly modified outer layer – leaving surrounding health tissue with minimum damage.

In Japan[4] work at Nagoya University with magnetite cationic liposomes (MCLs) combined with heat shock proteins has shown great potential in cancer treatment as well. Using the MCLs, the researchers demonstrated that they could locally generate heat in a tumor by placing test mice in an alternating magnetic field and not cause the body temperature of the test animal to rise. Following injection of the MCLs and application of an alternating magnetic field, tumor temperature and body temperature differed by 6ºC. The combined treatment strongly inhibited tumor growth over a 30-day period and complete regression of tumors was observed in 20% of the mice.

This parallel progress in applications of nanotechnology for the treatment of cancer illustrates the global interest in nanoscience and its potential application to innovative medical technologies. Further, the fact that several groups, using related but different techniques, can demonstrate positive results increases the chances that this new approach might be a powerful new approach to the treatment of cancer.

[1] “Photo-thermal tumor ablation in mice using near infrared-absorbing nanoparticles,” D.P. O’Neal, L.R. Hirsch, N.J. Halas, J.D. Payne, and J.L. West, Cancer Letters 209, 171-176 (2004)

[2] <http://www.germanyinfo.org/relaunch/info/publications/week/2003/030613/misc2.html (http://www.germany-info.org/relaunch/info/publications/week/2003/030613/misc2.html)>http://www.germany-info.org/relaunch/info/publications/week/2003/030613/misc2.html (http://www.germany-info.org/relaunch/info/publications/week/2003/030613/misc2.html)

[3] “Magnemite nanoparticles with very high AC-losses for application in RF-magnetic hyperthermia,” R. Hergt, R. Hiergeist, J. Hilger, W.A. Kaiser, Y. Lapatnikov, S. Margel, and U. Richter, J. Magnetism and Magnetic Materials 270, 345-357 (2004).

[4] “Hyperthermia using magnetic nanoparticles in an experimental subcutaneous murine melanoma,” A. Ito, F. Matsuoka, H. Honda, and T. Kobayashi, Cancer Immunology Immunotherapy 53 (1), 26-32 (2004).

http://www.nano.gov/html/news/SpecialPapers/Cancer%20Sidebar%20for%202005%20Budget%20Supplemen t.htm (http://www.nano.gov/html/news/SpecialPapers/Cancer%20Sidebar%20for%202005%20Budget%20Supplemen t.htm)

[abdulhakeem]

Shaping molecules intrigues scientists

BY BARNABY J. FEDER THE NEW YORK TIMES
Posted on Monday, November 8, 2004

Nanotechnology’s bag of tricks for inventing new molecules and manipulating those available naturally is increasingly drawing the attention of health-care researchers.

Evidence is accumulating that nanotechnology may allow better early warning systems for cancer and heart disease, cures for progressive diseases like cystic fibrosis, techniques for making implants like artificial hips more successful, and even artificial kidneys.

But there is no reliable timeline for the home-run projects, according to specialists like Dr. Peter R. Cavanagh, chairman of the department of biomedical engineering at the Cleveland Clinic Foundation, one of the nation’s largest hospital and health research centers. "We know how to make rubber, and we know where the road is going to go," Cavanagh recently told an international gathering of nanotechnology researchers and physicians at the Cleveland Clinic. "What we don’t know is where the rubber is going to meet the road."

Nanotechnology has garnered headlines and billions of dollars of federal investment because of its potentially broad effects on all parts of commerce. It is already used in consumer products like transparent sunscreens and stain-resistant clothing. But its capacity for mixing and matching molecules seems especially suited for transforming medicine.

Nanotechnology involves industrial products and processes in the realm of nanometers, or billionths of a meter. That is also the scale on which all living cells — and the things that nourish or kill them — operate. Viruses, for instance, range in size from 20 nanometers to 300 nanometers, with human antibodies roughly the size of smaller viruses.

Dr. H. David Humes at the University of Michigan and Dr. Tejal Desai at Boston University are using machinery and processes adapted from the semiconductor industry to build prototypes of implantable artificial organs with pores or slits smaller than 20 nanometers wide. Such nanofilters are the only way to let essential nutrients pass in and out of the devices while excluding cells and other biological matter that can clog or poison them.

Medical-device companies have also tinkered with the molecular structures of the surfaces of the materials they use. For devices like pacemakers, one goal is to make them less hospitable to in-growth from tissues that could impair the devices. In other cases, as with hip or knee implants, the engineers are trying to make the body’s tissues penetrate and bind to the surface as fast as possible.

In recent years, scanning electron microscopes and atomic force microscopes have allowed bioengineers to get sharper images of what they were doing. And computer-controlled machinery has given them the ability to manipulate the size, shape and surfaces of drugs and devices.

Now, for example, device makers not only shape the surfaces of their products, but they may also add specialty coatings like those from Biophan Technologies.

Biophan’s coatings, made up of magnetic particles 20 nanometers to 40 nanometers across, make the devices visible to magnetic resonance imaging machines used to track their placement.

The new tools inevitably conjure up Fantastic Voyage, the 1960s science-fiction thriller in which a medical team was shrunk to microscopic scale and launched into a patient’s bloodstream in a cell-size submarine to wipe out a blood clot in the victim’s brain.

Indeed, Dr. Aaron J. Fleischman, co-director of the laboratory that Cleveland Clinic set up five years ago to provide researchers with engineering support for very small-scale devices, said doctors initially asked him when he would start building tiny intelligent submarines — minus the shrunken crew, of course.

While researchers do discuss the feasibility of making tiny robotic devices able to maneuver inside the body and perform a variety of tasks, most current research and new product development is focused on nanoscale particles.

Quantum dots, metallic particles that emit bright light in a color range that varies with their size, are now frequently used to study tumors and locate proteins that researchers want to study. By attaching antibodies that prefer to bind with specific types of cells to dots of different sizes, the researchers can get a multicolored image showing the location and concentration of many elements inside a tissue sample.

Nanoparticles may also help researchers overcome roadblocks in gene therapy, which seeks to treat genetically inherited diseases like cystic fibrosis by implanting healthy genes to do the work of damaged genes.

Researchers working on cystic fibrosis, a fatal disease where the lack of a crucial protein produced by a single gene allows mucous to block airways in the lungs, have tried fruitlessly to use viruses to deliver healthy copies of the gene to patients ’ lungs.

Now Dr. Pamela B. Davis, a pediatrics professor at the Case Western Reserve University School of Medicine, and Copernicus Therapeutics, a startup company based in Cleveland, have shown that rods 15 nanometers wide and made of compacted DNA, the amino acid lysine and a common stomach fluid can safely transfer the gene into airway cells and, in animals, reduce symptoms of the disease.

Nanoparticles may also be used to deliver heat to cancer cells to kill them. MagForce Technologies, based in Berlin, coats iron oxide nanoparticles with a compound that is a nutrient for tumor cells, which then ingest the particles. When an external magnetic field causes the particles to vibrate rapidly, the tumor cells are killed and then flushed from the body by its natural scavenger cells, according to MagForce’s research results.

MagForce expects regulatory approval to sell the particles and its treatment machinery in Germany in 2006 after more extensive clinical trials have been completed. A German insurer has already agreed to reimburse hospitals there for the technology, based on early results, according to Dr. Andreas Jordan, the company’s chief executive.

Jordan said he was negotiating with large American equipment vendors in hopes of finding a partner big enough to cope with the costs of getting regulatory and reimbursement approval in the United States.

But business issues aside, researchers say, nanotechnology in medicine faces so many technical hurdles that long delays and numerous failures are inevitable. "The complexity of biology is clearly beyond our comprehension at this time," said Dr. James R. Baker Jr., director of the Center for Biologic Nanotechnology at the University of Michigan. "That’s why so many drugs fail."

http://www.nwanews.com/story.php?paper=adg&section=Business&storyid=98250