Targeted Delivery of Small Interfering RNA Using Reconstituted High-Density Lipoprotein Nanoparticles

• Main Authors: Mian M.K. Shahzad, Lingegowda S. Mangala, Hee Dong Han, Chunhua Lu, Justin Bottsford-Miller, Masato Nishimura, Edna M. Mora, Jeong-Won Lee, Rebecca L. Stone, Chad V. Pecot, Duangmani Thanapprapasr, Ju-Won Roh, Puja Gaur, Maya P. Nair, Yun-Yong Park, Nirupama Sabnis, Michael T. Deavers, Ju-Seog Lee, Lee M. Ellis, Gabriel Lopez-Berestein, Walter J. McConathy, Laszlo Prokai, Andras G. Lacko, Anil K. Sood
• Format: Article
• Language: English
• Published: Elsevier 2011-04-01
• Series: Neoplasia: An International Journal for Oncology Research
• Online Access: http://www.sciencedirect.com/science/article/pii/S1476558611800126
• ISSN: 1476-5586; 1522-8002

RNA interference 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 small interfering RNA (siRNA). To maintain a high level of growth, tumor cells scavenge high-density lipoprotein (HDL) 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 established a novel formulation of siRNA by incorporating it into reconstituted HDL (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 and focal adhesion kinase) 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.