Reconstituted HDL-siRNA Nanoparticles Block Cancer Growth in Mouse Models

Synthetic HDL (high-density lipoprotein) nanoparticles loaded with small interfering RNA (siRNA) have been used to inhibit growth of tumor cells in mouse models of ovarian and colorectal cancer.

Investigators at the University of Texas MD Anderson Cancer Center (Houston, USA) have been seeking an effective and nontoxic means for introducing gene-silencing miRNA into cancer cells. In this study, they exploited the need for cancer cells to take up large quantities of HDL through the SR-B1 receptor, which is overexpressed by many types of tumors. The only normal cells expressing this receptor are in the liver.

The investigators reported in the April 2011 issue of the journal Neoplasia that they had succeeded in establishing a novel formulation of siRNA by incorporating it into reconstituted high-density lipoprotein (rHDL) nanoparticles. They demonstrated that rHDL nanoparticles facilitated highly efficient systemic delivery of siRNA in vivo, mediated by the SR-B1 receptor. These nanoparticles were effective in silencing the expression of two proteins that are key to cancer growth and metastasis (signal transducer and activator of transcription 3 [STAT3] and focal adhesion kinase [FAK]) in mouse models of ovarian and colorectal cancer.

"RNA interference has great therapeutic potential but delivering it to cancer cells has been problematic,” said senior author Dr. Anil Sood, professor of cancer biology at the MD Anderson Cancer Center. "Combining siRNA with HDL provides an efficient way to get these molecules to their targets. If siRNA is not in a nanoparticle, it gets broken down and excreted before it can be effective. HDL is completely biocompatible and is a safety improvement over other types of nanoparticles. This study has several important implications in the ability to fight certain cancers.”

"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,” said Dr. Sood. ”Next, we will work with the [US] National Cancer Institute Nanoparticle Characterization Lab (Frederick, MD, USA) to develop a formulation of the HDL/siRNA nanoparticle for human use.”

Related Links:
University of Texas MD Anderson Cancer Center
National Cancer Institute Nanoparticle Characterization Lab