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.
authors.affiliation: Department of Gynecologic Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Mian M K
authors.initials: MM
authors.lastname: Shahzad
authors.forename: Lingegowda S
authors.initials: LS
authors.lastname: Mangala
authors.forename: Hee Dong
authors.initials: HD
authors.lastname: Han
authors.forename: Chunhua
authors.initials: C
authors.lastname: Lu
authors.forename: Justin
authors.initials: J
authors.lastname: Bottsford-Miller
authors.forename: Masato
authors.initials: M
authors.lastname: Nishimura
authors.forename: Edna M
authors.initials: EM
authors.lastname: Mora
authors.forename: Jeong-Won
authors.initials: JW
authors.lastname: Lee
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: Stone
authors.forename: Chad V
authors.initials: CV
authors.lastname: Pecot
authors.forename: Duangmani
authors.initials: D
authors.lastname: Thanapprapasr
authors.forename: Ju-Won
authors.initials: JW
authors.lastname: Roh
authors.forename: Puja
authors.initials: P
authors.lastname: Gaur
authors.forename: Maya P
authors.initials: MP
authors.lastname: Nair
authors.forename: Yun-Yong
authors.initials: YY
authors.lastname: Park
authors.forename: Nirupama
authors.initials: N
authors.lastname: Sabnis
authors.forename: Michael T
authors.initials: MT
authors.lastname: Deavers
authors.forename: Ju-Seog
authors.initials: JS
authors.lastname: Lee
authors.forename: Lee M
authors.initials: LM
authors.lastname: Ellis
authors.forename: Gabriel
authors.initials: G
authors.lastname: Lopez-Berestein
authors.forename: Walter J
authors.initials: WJ
authors.lastname: McConathy
authors.forename: Laszlo
authors.initials: L
authors.lastname: Prokai
authors.forename: Andras G
authors.initials: AG
authors.lastname: Lacko
authors.forename: Anil K
authors.initials: AK
authors.lastname: Sood
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D016503:Drug Delivery Systems / Q000379:methods*; D005260:Female; D020868:Gene Silencing / Q000502:physiology; D015316:Genetic Therapy / Q000379:methods; D045325:HCT116 Cells; D006801:Humans; D008075:Lipoproteins, HDL / Q000737:chemistry* / Q000493:pharmacokinetics*; D051379:Mice; D008819:Mice, Nude; D008863:Microspheres; D008954:Models, Biological; D053758:Nanoparticles / Q000737:chemistry; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D008075:Lipoproteins, HDL; D034741:RNA, Small Interfering