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

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

来源：Nanomedicine: Nanotechnology, Biology and Medicine , 2014, 10(5): 897-900.

DOI：10.1016/j.nano.2014.03.006

• Lipid-polymer nanoparticle
• siRNA
• Sustained release
• Gene silencing
• Cancer

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.

• 出版日期2014-7
• 单位四川大学