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RNA Nanoparticles Reduce Ovarian Tumors
By loading fragile RNA into silicon nanoparticles, researchers at the Methodist Hospital in Houston, Texas, have found that the new drug delivery system can reduce the size of ovarian tumors by as much as 83% and can stop tumor growth in chemotherapy-resistant ovarian cancer tissue.
The new study, conducted in animal models, was published online in Clinical Cancer Research.
“Drug resistance is a huge problem in the clinic,” said senior author Mauro Ferrari, PhD. “Our work shows that protecting the RNA longer so that it can get to where it must go and do its work inside cancer cells not only increases the RNA’s impact, but also makes drug-resistant cancer cells once again sensitive to commonly used chemotherapy drugs.”
Small inhibitory RNA (siRNA) is a snippet of genetic material that interferes with the expression of genes — in this case, a crucial ovarian cancer gene called ephA2. The researchers are using siRNA as a drug to stop cancer cells from growing and eventually to kill them.
While safe, siRNA can’t simply be injected into a patient. Enzymes in the blood and inside cells can destroy the siRNA before it gets close to its target cancer cells. Therefore, a protective shield for the siRNA — a lipid-carrier nanoparticle called a nanoliposome — was developed at the M.D. Anderson Cancer Center.
In the new study, the researchers learned that the liposome-clad siRNA was more likely to reach cancer cells (where the liposome would be absorbed) — but the liposomes usually didn’t last very long in the blood. For any cancer therapy to be effective, the researchers decided that a more sustained drug delivery method was needed.
Ferrari and his colleagues therefore developed disc-shaped, silicon nanoparticles (1 micrometer in diameter) that are designed to bind to tumor cells. Past studies had helped them perfect the shape of the particles, their size, and their surface chemistry so that the particles can bind specifically to over-expressed proteins dotting the outside of cancer cells.
Twelve injections of 5, 10, or 15 mcg of the nanoparticles over 6 weeks reduced ovarian cancer tumor weight by 36%, 64%, and 83%, respectively, in each of three groups of animals compared with control animals that received placebo. The scientists also saw a reduction in the number of tumor nodules in each of the three treatment groups compared with controls.
When the nanoparticles were injected with the common first- and second-line chemotherapy drug paclitaxel, the researchers saw zero tumor growth.
Source: The Methodist Hospital System; February 13, 2013.