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

Overview

Journal Neoplasia

Publisher Elsevier

Specialty Oncology

Date 2011 Apr 8

PMID 21472135

Citations 102

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

Affiliations

Soon will be listed here.

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.

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