creative way to deliver silencing RNA to tumors via "GOOD" cholesterol nanoparticles!

[Lani]

ABSTRACT: 'Good Cholesterol' Nanoparticles Seek and Destroy Cancer Cells
[MD Anderson Cancer Center]

High-density lipoprotein's hauls excess cholesterol to the liver for disposal, but new research suggests "good cholesterol" can also act as a special delivery vehicle of destruction for cancer.

Synthetic HDL nanoparticles loaded with small interfering RNA to silence cancer-promoting genes selectively shrunk or destroyed ovarian cancer tumors in mice, a research team led by scientists from The University of Texas MD Anderson Cancer Center and the University of North Texas Health Science Center reports in the April edition of Neoplasia.

"RNA interference has great therapeutic potential but delivering it to cancer cells has been problematic," said 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. "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."

Sood and Andras Lacko, Ph.D., professor of Molecular Biology and Immunology at UNT Health Science Center, jointly developed the nanoparticles, which build on Lacko's original insight about HDL's potential for cancer drug delivery.

The next step is to prepare for human clinical trials, the two scientists said. "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.


OPEN ACCESS: Targeted Delivery of Small Interfering RNA Using Reconstituted High-Density Lipoprotein Nanoparticles (PDF)
[Neoplasia]

RNA interference (RNAi) holds tremendous potential as a therapeutic approach, especially in the treatment of malignant tumors. However, efficient and biocompatible delivery methods are needed for systemic delivery of siRNA. To maintain a high level of growth, tumor cells scavenge high density lipoprotein particles by overexpressing its receptor: scavenger receptor type B1 (SR-B1). In this study, we exploited this cellular characteristic to achieve efficient siRNA delivery and have established a novel formulation of siRNA by incorporating it into reconstituted high density lipoprotein (rHDL) nanoparticles. Here, we demonstrate that rHDL nanoparticles facilitate highly efficient systemic delivery of siRNA in vivo, mediated by the SR-B1. Moreover, in therapeutic proof-of-concept studies, 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 orthotopic mouse models of ovarian and colorectal cancer. These data indicate that an rHDL nanoparticle is a novel and highly efficient siRNA carrier, and therefore this novel technology could serve as the foundation for new cancer therapeutic approaches.