Jul 17, 2012 |
With drug-loaded nanogel, researchers attack cancerous tumors
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(Nanowerk News) Yale University scientists have developed a new mechanism for attacking cancerous tumors that intensifies the body’s immune response while simultaneously weakening the tumor’s ability to resist it.
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“We believe this is a paradigm-changing immunotherapeutic method for cancer therapy,” said Tarek M. Fahmy, a bioengineer at Yale and the project’s principal investigator. “In essence, it’s a one-two punch strategy that seems to work well for melanoma and may work even better with other cancers.”
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The researchers report results July 15 online in the journal Nature Materials ("Combination delivery of TGF-β inhibitor and IL-2 by nanoscale liposomal polymeric gels enhances tumour immunotherapy"). Dr. Richard A. Flavell of Yale School of Medicine and the Howard Hughes Medical Institute collaborated on the project.
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This illustration depicts a nanolipogel administering its immunotherapy cargo. The light-blue spheres within the blood vessels and the cutaway sphere in the foreground are the nanolipogels. (Illustration by Nicolle Rager Fuller, NSF)
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Tumors — in this case metastatic melanomas, or spreading skin cancers — are adept at overcoming their host’s natural defenses, in part by emitting agents that disrupt production and operation of the immune system.
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The Yale team developed a new biodegradable nanoparticle that delivers a combination of two very different therapeutic agents to tumor sites, gradually releasing the agents into the tumor vasculature. One agent, a large soluble protein called a cytokine, stimulates the body’s innate immune response. The other, a small-molecule inhibitor, interferes with the tumor’s ability to suppress the immune response. Other drug combinations are possible.
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In tests on live mice, the double-loaded particle, called a nanogel, significantly delayed tumor growth and increased survival, the researchers report. They administered the nanogels intravenously and, in separate experiments, directly into the tumors. Further animal tests are planned.
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The main challenge researchers faced was devising a particle that enabled gradual, sustained release of two therapeutic agents with very different properties: the protein, which readily dissolves in the body, and the small-molecule drug, which doesn’t. Researchers describe the materials and unique structure of their solution in the Nature Materials paper.
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They exclusively used components already approved by the U.S. Food and Drug Administration. This could potentially expedite future experiments with other ingredients and human trials, they said.
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