Showing posts with label cancer therapy. Show all posts
Showing posts with label cancer therapy. Show all posts

Sunday, November 29, 2009

Conquering cancer with implants? Bioengineered vaccines and magnetic nanodiscs show promise

Nov 29, 2009 01:01 PM in Health & Medicine | Post a comment

By Katherine Harmon

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cancer vaccine implantRather than surgically removingtumors, what if doctors could simply implant new tools in our bodies to do the work internally? One team of researchers has been able to vanquish tumors in mice by implanting bioengineered disks filled with tumor-specific antigens, and another has developed magnetized nanodiscs to induce cancer cells destroy themselves.

Numerous
cancer vaccines have shown promise in animal models only to later fail to generate results in humans. But an implant-based approach may hold the key, according to a team of immunologists and bioengineers at Harvard University. They designed a tiny polymer disk saturated with dendritic cells and antigens specifically tuned to go after tumor cells. The results, published online November 25 in Science Translational Medicine, show "the power of applying engineering approaches to immunology," David Mooney, a professor of bioengineering ant Harvard's School of Engineering and Applied Sciences, said in a prepared statement.

The principal is the same as a vaccine: prompt the immune system to attack invading cells. However, unlike previously tested injected cancer vaccines, cells from the disk are less prone to die before they can get the job done.

The 8.5-millimeter biodegradable disk can be "inserted anywhere under the skin—much like the implantable contraceptives that can be placed in a woman's arm," Mooney said. "The implants activate an immune response that destroys tumor cells." When the disks were implanted in mice with melanoma, the treatment led to remission and longer lives in "a substantial portion of the population," the authors reported.

Another trick to zapping cancer cells may lie in
nano-scale magnets. Previous studies have investigated the use of magnetic fields to kill cancer cells via hyperthermia, but they required a lot more power than the new method and proved to have some dangerous side effects.

A new study, published November 29 in
Nature Materials, reports promise in a scaled-down version of this idea to tackle tumors. "Nanomagnetic materials offer exciting avenues for probing cell mechanics and…advancing cancer therapies," the paper authors wrote. Using nanodiscs (about 60 nanometers thick) made of iron and nickel, researchers based in the Argonne National Laboratory in Illinois and the University of Chicago Pritzker School of Medicine have created a so-called "magnetic vortex" in the magnetic alloy with the magnetic charge arranged in concentric circles. "Integration of magnetic materials with biological molecules and therapeutics creates hybrid materials with advanced properties," the authors noted in the paper.

By introducing an alternating magnetic field, researchers made the discs oscillate, thereby damaging the membranes of cancer cells in the lab and causing the cells to die. The researchers needed only a frequency of "a few tens of hertz applied for only 10 minutes" to "achieve cancer-cell destruction
in vitro," they wrote. With this approach they rely on neither heat nor mechanical assault, but rather on the oscillation "which triggers the programmed cell-death pathway" via an ionic electrical signal, the authors explained. Thus, "the total energy necessary to accomplish cell death is minute."

While these innovative implant technologies are being tested in the lab, however, cancer continues to be one of the leading causes of death in the U.S. (second only to heart disease), killing more than half a million people last year.

Image of polymer matrix (next to dime for size comparison) courtesy of InCytu, Inc.

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Tuesday, September 22, 2009

Therapeutic Nanoparticles Give New Meaning to Sugar-Coating Medicine

Published on 22 September 2009

A research team at the National Institute of Standards and Technology (NIST) studying sugar-coated nanoparticles for use as a possible cancer therapy has uncovered a delicate balancing act that makes the particles more effective than conventional thinking says they should be. Just like individuals in a crowd respecting other people’s personal space, the particles work because they get close together, but not too close.

In cooperation with colleagues at The Johns Hopkins University, Dartmouth College, the University of Manitoba and two biopharmaceutical companies, the NIST team has demonstrated* that the particles—essentially sugar-coated bits of iron oxide, about 100 nanometers wide—are potent cancer killers because they interact with one another in ways that smaller nanoparticles do not. The interactions, thought by many bioengineers to be undesirable, actually help the larger particles heat up better when subjected to an alternating magnetic field. Because this heat destroys cancer cells, the team’s findings may help engineers design better particles and treatment methods.

Nanoparticles hold the promise of battling cancer without the damaging side effects of chemotherapy or radiation treatment. Minuscule balls of iron oxide can be coated with sugar molecules making them particularly attractive to resource-hungry cancer cells. Once the particles are injected, cancer cells would then ingest them, and doctors would then be able to apply an alternating magnetic field that causes the iron oxide centers to heat, killing the cancer but leaving surrounding tissue unharmed.

Two biotech companies, Micromod Partikeltechnologie and Aduro BioTech, created particles that showed great potential in treating cancers in mice, and they asked NIST to help understand why it worked so well. “But they sent us particles that were much larger than what the conventional wisdom says they should be,” says NIST materials scientist Cindi Dennis. “Larger particles are more strongly magnetic and tend to clump together, which makes them large enough to attract the body’s defense systems before they can reach a tumor. The companies’ nanoparticles, however, did not have this problem.”

Neutron scattering probes at the NIST Center for Neutron Research revealed that the particles’ larger iron oxide cores attract one another, but that the sugar coating has fibers extending out, making it resemble a dandelion—and these fibers push against one another when two particles get too close together, making them spring apart and maintain an antibody-defying distance rather than clumping. Moreover, when the particles do get close, the iron oxide centers all rotate together under the influence of a magnetic field, both generating more heat and depositing this heat locally. All these factors helped the nanoparticles destroy breast tumors in three out of four mice after one treatment with no regrowth.


An iron-centered nanoparticle (left) analyzed at NIST’s Center for Neutron Research has a coating of the sugar dextran, whose tendrils prevent groups of the particles from clumping. When tumor cells ingest them (right), the particles still congregate closely enough to share heat when stimulated by a magnetic field, killing the cells. White arrow indicates a red blood cell. View hi-resolution image
Credit: (l.) J. Aarons; (r.) A. Guistini, R. Strawbridge and P. Hoopes, Dartmouth College


“The push-pull is part of a tug of war that fixes the distance between nanoparticles,” Dennis says. “This suggests we can stabilize interacting particles in ways that potentially pay off in the clinic.”

The research was funded by the U.S. Army Medical Research and Materiel Command and used facilities supported by the National Science Foundation.

* C.L. Dennis, A.J. Jackson, J.A. Borchers, P.J. Hoopes, R. Strawbridge, A.R. Foreman, J. van Lierop, C. Gruttner and R. Ivkov. Nearly complete regression of tumors via collective behavior of magnetic nanoparticles in hyperthermia. Nanotechnology, 20 (2009) 395103. [doi:10.1088/0957-4484/20/39/395103]

Contact: Chad Boutin, boutin@nist.gov, (301) 975-4261

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