Nanoparticle containing drug that fights cancer genes developed

Washington, Sept 16 : Scientists at Penn State College of Medicine have devised a safer and more effective way of targeting cancer-causing genes in cancer cells.

They have administered nanoparticles filled with a drug that targets two genes that trigger melanoma cancer.

According to the scientists, the nanomedical approach could offer a potential cure for the cancer.

The new treatment is administered through an ultrasound device and targets cancer-causing genes in cancer cells without harming normal tissue.

"It is a very selective and targeted approach. And unlike most other cancer drugs that inadvertently affect a bunch of proteins, we are able to knock out single genes," said Gavin Robertson, associate professor of pharmacology, pathology and dermatology, Penn State College of Medicine.

They thought that "silencing RNA" (siRNA), strands of RNA molecules that knock out specific genes, could turn off the two cancer-causing genes and potentially treat the deadly disease more effectively.

"siRNA checks the expression of the two genes, which then lowers the abnormal levels of the cancer causing proteins in cells," explained Robertson, who is lead author of the study.

Recently, researchers have closed 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.

They also found earlier that a protein called Akt3 regulates the activity of the mutated B-Raf, which aids the development of melanoma.

Robertson said that the drug used specifically targets Akt3 and the mutant B-Raf and therefore does not affect normal cells.

However, it's not easy to knock out specific genes, for delivering the siRNA drug to cancerous cells is rather difficult, as protective layers in the skin not only keep drugs out, but chemicals in the skin quickly degrade the siRNA.

In order to ward off these two problems, the researchers engineered hollow nano-sized particles -- nanoliposomes -- from globes of fatty acids into which they packed the siRNA.

Later, they used a portable ultrasound device to temporarily create microscopic holes in the surface of the skin, which would enable the drug-filled particles to leak into tumour cells beneath.

"Think of it as tiny basketballs that each protect the siRNA inside from getting degraded by the skin. 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," explained Robertson.

When they 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.

"This is essentially human skin with human melanoma cells, which provides an accurate picture of how the drug is acting. If you knock down each of these two genes separately, you are able to reduce tumor development somewhat. But knocking them down together leads to synergistic reduction of tumor development," said Robertson.

The study appeared in the latest issue of the journal Cancer Research.

ANI