HDL cholesterol nanoparticle system developed for cancer treatment

Kathleen Blanchard's picture
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Synthetic HDL delivers RNA to silence cancer genes

Researchers from The University of Texas MD Anderson Cancer Center and the University of North Texas Health Science Center report they have developed a synthetic HDL cholesterol, combined with nanoparticles that interfere with RNA to silence cancer. HDL cholesterol can be used as a "special delivery system" to seek out and destroy cancer cells.

Anil Sood, M.D., the study's senior author and MD Anderson's director of Ovarian Cancer Research and co-director of the Center for RNA Interference and Non-Coding RNA at MD Anderson and Andras Lacko, Ph.D., professor of Molecular Biology and Immunology at UNT Health Science Center developed the nanoparticles that they plan to study in human clinical trials.

Synthetic HDL efficiently delivers cancer therapy

Dr. Sood explains, "RNA interference has great therapeutic potential but delivering it to cancer cells has been problematic. Combining siRNA with HDL provides an efficient way to get these molecules to their targets. This study has several important implications in the ability to fight certain cancers."

Using HDL in combination with RNA to destroy cancer cells would mean an entirely new approach that Sood says would benefit patients with a new type of treatment.

"If we can knock out 70, 80 or 90 percent of tumors without drug accumulation in normal tissues in mice, it is likely that many cancer patients could benefit from this new type of treatment in the long run," Lacko said.

Cancer and liver cells attract HDL cholesterol

Cancer cells produce a receptor that attracts HDL cholesterol, known as SR-B1. When HDL cholesterol combines with cancer cells, they grow and spread.

Healthy cells are protected from RNA interference with the nanoparticle treatment because only cancer and liver cells have SR-B1 receptors.

Synthetic HDL safer way to treat cancer

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The researchers explain they developed the synthetic HDL, called rHDL, because it's more stable than the natural version - rHDL can block and treat spread of cancer to the liver and stays in the circulatory system longer, making it a better option than natural HDL. The researchers say the synthetic rHDL is also safer than other drug formulations because it doesn't interfere with the immune system.

Delivering siRNA in a nanoparticle makes it more stable. Sood says without the tiny particles it is broken down and excreted before it can be effective.

In the mouse studies, the researchers found rHDL is taken up by 80 percent of treated tumors with little or no liver toxicity. The researchers used siRNA targeted to specific genes that promote ovarian cancer growth and spread.

Combination siRNA/rHDL shrinks tumors

The combination of the siRNA/rHDL nanoparticle formulation with chemotherapy reduced tumor size by 90 percent. Without chemotherapy, the RNA interfering, synthetic HDL combination shrunk tumors 60 to 80 percent.

The FAK gene that was targeted is overexpressed in colorectal, breast, ovarian, thyroid and prostate cancers and makes ovarian cancer especially aggressive explain the researchers. Other therapies targeting the STAT3 gene implicated for cancer growth have had limited success. Using synthetic HDL to deliver cancer therapy is tumor specific and less likely to harm normal tissue.

"In order to help expedite the study's progress to a clinical setting, we have identified 12 genes as biomarkers for response to STAT3-targeted therapy," Sood said. "Next, we'll work with the National Cancer Institute Nanoparticle Characterization Lab to develop a formulation of the HDL/siRNA nanoparticle for human use."

The researchers have applied for a patent for the synthetic HDL nanoparticle delivery system. Using a synthetic form of HDL cholesterol that naturally finds cancer cells then destroys them by disrupting RNA production is a new and non toxic treatment approach.

Neoplasia
"Targeted Delivery of Small Interfering RNA Using rHDL Nanoparticles"
Mian M.K. Shahzad, Lingegowda S. Mangala, Hee D. Han et.al.

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