Authors:
Mian M.K. Shahzad, Lingegowda S. Mangala, Hee D. Han, Chunhua Lu, Justin Bottsford-Miller, Edna M. Mora, Jeong W. Lee, Rebecca L. Stone, Duangmani Thanapprapasr, Ju-Won Roh, Puja Gaur, Maya P. Nair, Yun Y. Park, Nirupama Sabnis, Michael T. Deavers, Ju-Seog Lee, Lee M. Ellis, Gabriel Lopez-Berestein, Walter J. McConathy, Laszlo Prokai, Andras G. Lacko, and Anil K Sood
Summary:
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.
Source:
Neoplasia; Vol. 13, Issue 4 (2011)