Targeted delivery of small interfering RNA using reconstituted high-density lipoprotein nanoparticles

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-BeresteiWalter J. McConathy, Laszlo Prokai, Andras G. Lacko, Anil K. Sood

Research output: Contribution to journalArticlepeer-review

154 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)309-319
Number of pages11
JournalNeoplasia
Volume13
Issue number4
DOIs
StatePublished - Apr 2011

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