Nanoparticles filled with a drug targeting two genes that trigger melanoma could offer a potential cure for this deadly disease, according to Penn State cancer researchers. The treatment, administered through an ultrasound device, demonstrates a safer and more effective way of targeting cancer-causing genes in cancer cells without harming normal tissue.
The researchers speculated that silencing RNA (siRNA) could turn off the two cancer-causing genes and potentially treat the deadly disease more effectively. In recent years, researchers have zeroed in on two key genes—B-Raf and Akt3—that cause melanoma. B-Raf, the most frequently mutated gene in melanoma, produces the mutant protein, B-Raf, which helps mole cells survive and grow but does not form melanomas on its own. Researchers previously found that a protein called Akt3 regulates the activity of the mutated B-Raf, which aids the development of melanoma.
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 Cancer Institute. However, delivering the siRNA drug to cancerous cells is difficult because protective layers in the skin keep drugs out, and chemicals in the skin quickly degrade the siRNA.
The researchers engineered hollow nano-sized particles—nanoliposomes—from globes of fatty acids into which they packed the siRNA. They 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.
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 to 70 percent, and more than halved the size of lesions after three weeks.
Mice with melanoma that underwent the same treatment had their tumors shrink by nearly 30 percent when only the mutant B-Raf was targeted. There was no difference in the development of melanoma when the Akt3 gene alone was targeted, although existing tumors shrank by about 10 to 15 percent 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 to 70 percent more than when either gene was targeted alone.
Release date: September 15, 2008
Source: Penn State University http://live.psu.edu/story/34545
