@article{6b52cce5d75045c882db02a09d88adf8,
title = "Targeted delivery of small interfering RNA using reconstituted high-density lipoprotein nanoparticles",
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.",
author = "Shahzad, {Mian M.K.} and Mangala, {Lingegowda S.} and Han, {Hee Dong} and Chunhua Lu and Justin Bottsford-Miller and Masato Nishimura and Mora, {Edna M.} and Lee, {Jeong Won} and Stone, {Rebecca L.} and Pecot, {Chad V.} and Duangmani Thanapprapasr and Roh, {Ju Won} and Puja Gaur and Nair, {Maya P.} and Park, {Yun Yong} and Nirupama Sabnis and Deavers, {Michael T.} and Lee, {Ju Seog} and Ellis, {Lee M.} and Gabriel Lopez-Berestei and McConathy, {Walter J.} and Laszlo Prokai and Lacko, {Andras G.} and Sood, {Anil K.}",
note = "Funding Information: Abbreviations: FBS, fetal bovine serum; MVD, microvessel density Address all correspondence to: Anil K. Sood, MD, Departments of Gynecologic Oncology and Cancer Biology, University of Texas MD Anderson Cancer Center, 1155 Herman Pressler, Unit 1362, Houston, TX 77030. E-mail: asood@mdanderson.org 1This research was supported by the GCF Molly-Cade ovarian cancer research grant, grants from the National Institutes of Health (Baylor WRHR Scholarship grant: HD050128; CA109298, CA110793, CA128797, RC2GM092599, U54 CA151668), NCI (T32 training grants CA 101642, CA 009614), Department of Defense (OC073399, OC093146, BC085265), a Program Project Development Grant from the Ovarian Cancer Research Fund, Inc, the Zarrow Foundation, The Marcus Foundation, the University of Texas MD Anderson Cancer Center SPORE in Ovarian Cancer (P50 CA083639), the Betty Ann Asche Murray Distinguished Professorship, Deborah Gonzalez Women{\textquoteright}s Health Fellowship Award, the Puerto Rico Comprehensive Cancer Center, Cowtown Cruisin{\textquoteright} for the Cure, and a HER grant from the University of North Texas Health Science Center. 2This article refers to supplementary materials, which are designated by Table W1 and Figures W1 to W6 and are available online at www.neoplasia.com. Received 21 September 2010; Revised 22 January 2011; Accepted 24 January 2011 Copyright {\textcopyright} 2011 Neoplasia Press, Inc. All rights reserved 1522-8002/11/$25.00 DOI 10.1593/neo.101372",
year = "2011",
month = apr,
doi = "10.1593/neo.101372",
language = "English (US)",
volume = "13",
pages = "309--319",
journal = "Neoplasia",
issn = "1522-8002",
publisher = "Elsevier Inc.",
number = "4",
}