Hybrid lipid-polymer nanoparticles for sustained siRNA delivery and gene silencing

Jinjun Shi; Yingjie Xu; Xiaoyang Xu; Xi Zhu; Eric Pridgen; Jun Wu; Alexander R Votruba; Archana Swami; Bruce R Zetter; Omid C Farokhzad

doi:10.1016/j.nano.2014.03.006

Hybrid lipid-polymer nanoparticles for sustained siRNA delivery and gene silencing

Nanomedicine. 2014 Jul;10(5):897-900. doi: 10.1016/j.nano.2014.03.006. Epub 2014 Mar 17.

Authors

Jinjun Shi¹, Yingjie Xu², Xiaoyang Xu³, Xi Zhu⁴, Eric Pridgen⁵, Jun Wu³, Alexander R Votruba³, Archana Swami³, Bruce R Zetter⁶, Omid C Farokhzad⁷

Affiliations

¹ 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.
² Vascular Biology Program, Children's Hospital Boston, Harvard Medical School, Boston, MA, USA.
³ Laboratory of Nanomedicine and Biomaterials, Department of Anesthesiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
⁴ 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.
⁵ Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
⁶ Vascular Biology Program, Children's Hospital Boston, Harvard Medical School, Boston, MA, USA. Electronic address: bruce.zetter@childrens.harvard.edu.
⁷ 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.

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.

From the clinical editor: 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.

Keywords: Cancer; Gene silencing; Lipid–polymer nanoparticle; Sustained release; siRNA.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Cell Line, Tumor
Gene Silencing
HeLa Cells
Humans
Lipids / chemistry*
Nanoparticles / chemistry*
Polymers / chemistry*
Prohibitins
RNA, Small Interfering

Substances

Lipids
PHB protein, human
Polymers
Prohibitins
RNA, Small Interfering

Abstract

Publication types

MeSH terms

Substances

Grants and funding