TY - JOUR
T1 - Targeted delivery of small interfering RNA using reconstituted high-density lipoprotein nanoparticles
AU - Shahzad, Mian M K
AU - Mangala, Lingegowda S.
AU - Han, Hee Dong
AU - Lu, Chunhua
AU - Bottsford-Miller, Justin
AU - Nishimura, Masato
AU - Mora, Edna M.
AU - Lee, Jeong Won
AU - Stone, Rebecca L.
AU - Pecot, Chad V.
AU - Thanapprapasr, Duangmani
AU - Roh, Ju Won
AU - Gaur, Puja
AU - Nair, Maya P.
AU - Park, Yun Yong
AU - Sabnis, Nirupama
AU - Deavers, Michael T.
AU - Lee, Ju Seog
AU - Ellis, Lee M.
AU - Lopez-Berestei, Gabriel
AU - McConathy, Walter J.
AU - Prokai, Laszlo
AU - Lacko, Andras G.
AU - Sood, Anil K.
N1 - 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’s Health Fellowship Award, the Puerto Rico Comprehensive Cancer Center, Cowtown Cruisin’ 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 © 2011 Neoplasia Press, Inc. All rights reserved 1522-8002/11/$25.00 DOI 10.1593/neo.101372
Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 2011/4
Y1 - 2011/4
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=79953679621&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79953679621&partnerID=8YFLogxK
U2 - 10.1593/neo.101372
DO - 10.1593/neo.101372
M3 - Article
C2 - 21472135
AN - SCOPUS:79953679621
VL - 13
SP - 309
EP - 319
JO - Neoplasia (United States)
JF - Neoplasia (United States)
SN - 1522-8002
IS - 4
ER -