title: Hybrid lipid-polymer nanoparticles for sustained siRNA delivery and gene silencing.
abstract: The development of controlled-release nanoparticle (NP) technologies has great potential to further improve the therapeutic efficacy of RNA interference (RNAi), by prolonging the release of small interfering RNA (siRNA) for sustained, long-term gene silencing. Herein, we present an NP platform with sustained siRNA-release properties, which can be self-assembled using biodegradable and biocompatible polymers and lipids. The hybrid lipid-polymer NPs showed excellent silencing efficacy, and the temporal release of siRNA from the NPs continued for over one month. When tested on luciferase-expressed HeLa cells and A549 lung carcinoma cells after short-term transfection, the siRNA NPs showed greater sustained silencing activity than lipofectamine 2000-siRNA complexes. More importantly, the NP-mediated sustained silencing of prohibitin 1 (PHB1) generates more effective tumor cell growth inhibition in vitro and in vivo than the lipofectamine complexes. We expect that this sustained-release siRNA NP platform could be of interest in both fundamental biological studies and clinical applications.
  
  
  BACKGROUND
  Emerging gene silencing applications could be greatly enhanced by prolonging the release of siRNA for sustained gene silencing. This team of scientists presents a hybrid lipid-polymer nanoparticle platform that successfully accomplishes this goal, paving the way to future research studies and potential clinical applications.
authors.affiliation: Laboratory of Nanomedicine and Biomaterials, Department of Anesthesiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. Electronic address: jinjun.shi@zeus.bwh.harvard.edu.
authors.forename: Jinjun
authors.initials: J
authors.lastname: Shi
authors.affiliation: Vascular Biology Program, Children's Hospital Boston, Harvard Medical School, Boston, MA, USA.
authors.forename: Yingjie
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Laboratory of Nanomedicine and Biomaterials, Department of Anesthesiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Xiaoyang
authors.initials: X
authors.lastname: Xu
authors.affiliation: Laboratory of Nanomedicine and Biomaterials, Department of Anesthesiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; Key Laboratory of Drug Targeting and Drug Delivery System, West China School of Pharmacy, Sichuan University, Chengdu, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
authors.forename: Eric
authors.initials: E
authors.lastname: Pridgen
authors.affiliation: Laboratory of Nanomedicine and Biomaterials, Department of Anesthesiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Wu
authors.affiliation: Laboratory of Nanomedicine and Biomaterials, Department of Anesthesiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Alexander R
authors.initials: AR
authors.lastname: Votruba
authors.affiliation: Laboratory of Nanomedicine and Biomaterials, Department of Anesthesiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Archana
authors.initials: A
authors.lastname: Swami
authors.affiliation: Vascular Biology Program, Children's Hospital Boston, Harvard Medical School, Boston, MA, USA. Electronic address: bruce.zetter@childrens.harvard.edu.
authors.forename: Bruce R
authors.initials: BR
authors.lastname: Zetter
authors.affiliation: Laboratory of Nanomedicine and Biomaterials, Department of Anesthesiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; King Abdulaziz University, Jeddah, Saudi Arabia. Electronic address: ofarokhzad@zeus.bwh.harvard.edu.
authors.forename: Omid C
authors.initials: OC
authors.lastname: Farokhzad
mesh_terms: D045744:Cell Line, Tumor; D020868:Gene Silencing; D006367:HeLa Cells; D006801:Humans; D008055:Lipids / Q000737:chemistry*; D053758:Nanoparticles / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry*; D000091402:Prohibitins; D034741:RNA, Small Interfering
chemical_list: D008055:Lipids; C000717328:PHB protein, human; D011108:Polymers; D000091402:Prohibitins; D034741:RNA, Small Interfering
keywords: Cancer; Gene silencing; Lipid–polymer nanoparticle; Sustained release; siRNA