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Researchers Use Nanoparticles in Melanoma Treatment
Posted: September 18, 2008
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The drug in this study specifically targets Akt3 and the mutant B-Raf and does therefore not affect normal cells, added Robertson, who is also director of the Foreman Foundation Melanoma Therapeutics Program at the Penn State College of Medicine Cancer Institute.
However, while knocking out specific genes may seem like a straightforward task, delivering the siRNA drug to cancerous cells is another story, because protective layers in the skin not only keep drugs out, but chemicals in the skin quickly degrade the siRNA. To clear these two hurdles, Robertson and his team engineered hollow nano-sized particles--nanoliposomes--from globes of fatty acids into which they packed the siRNA. Next, the researchers used a portable ultrasound device to temporarily create microscopic holes in the surface of the skin, allowing the drug-filled particles to leak into tumor cells beneath. "Think of it as tiny basketballs that each protect the siRNA inside from getting degraded by the skin," explained Robertson. "These basketballs fall through the holes created by the ultrasound and are taken up by the tumor cells, thereby delivering the siRNA drug into the tumor cells."
When the researchers exposed lab-generated skin, made from human connective tissue, containing early cancerous lesions to the treatment 10 days after the skin was created, the siRNA reduced the ability of cells containing the mutant B-Raf to multiply by nearly 60-70%, and more than halved the size of lesions after three weeks. "This is essentially human skin with human melanoma cells, which provides an accurate picture of how the drug is acting," said Robertson.
Mice with melanoma that underwent the same treatment had their tumors shrink by nearly 30% when only the mutant B-Raf was targeted. There was no difference in the development of melanoma when the Akt3 gene alone was targeted, though existing tumors shrank by about 10-15% in two weeks. However, when the researchers targeted both the Akt3 and the mutant B-Raf at the same time, they found that tumors in the mice shrank about 60-70% more than when either gene was targeted alone.
"If you knock down each of these two genes separately, you are able to reduce tumor development somewhat," Robertson said. "But knocking them down together leads to synergistic reduction of tumor development."