Hybrid lipid–polymer nanoparticles for sustained siRNA delivery and gene silencing
Votruba, Alexander R.
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CitationShi, Jinjun, Yingjie Xu, Xiaoyang Xu, Xi Zhu, Eric Pridgen, Jun Wu, Alexander R. Votruba, Archana Swami, Bruce R. Zetter, and Omid C. Farokhzad. 2014. “Hybrid Lipid–polymer Nanoparticles for Sustained siRNA Delivery and Gene Silencing.” Nanomedicine: Nanotechnology, Biology and Medicine 10 (5) (July): e897–e900. doi:10.1016/j.nano.2014.03.006.
AbstractThe 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 a 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.
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