Int. J. Mol. Sci. 2012, 13(1), 516-533; doi:10.3390/ijms13010516
Article

Biodegradable Nanoparticles of mPEG-PLGA-PLL Triblock Copolymers as Novel Non-Viral Vectors for Improving siRNA Delivery and Gene Silencing

Jing Du 1 email, Ying Sun 2 email, Qiu-Sheng Shi 1 email, Pei-Feng Liu 2 email, Ming-Jie Zhu 2 email, Chun-Hui Wang 3 email, Lian-Fang Du 1,* email and You-Rong Duan 2,* email
1 Department of Ultrasound, Shanghai First People’s Hospital Affiliated to Shanghai Jiaotong University School of Medicine, 85 Wu Jin Road, Shanghai 200080, China 2 Cancer Institute of Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine, 2200 Xie Tu Road, Shanghai 200032, China 3 Sino-American United Biotechnology Institute Co., Ltd, 15 Zhong Jiang Road, Shanghai 200032, China
* Authors to whom correspondence should be addressed.
Received: 24 October 2011; in revised form: 8 November 2011 / Accepted: 28 December 2011 / Published: 4 January 2012
(This article belongs to the Section Material Sciences and Nanotechnology)
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Abstract: Degradation of mRNA by RNA interference is one of the most powerful and specific mechanisms for gene silencing. However, insufficient cellular uptake and poor stability have limited its usefulness. Here, we report efficient delivery of siRNA via the use of biodegradable nanoparticles (NPs) made from monomethoxypoly(ethylene glycol)-poly(lactic-co-glycolic acid)-poly-l-lysine (mPEG-PLGA-PLL) triblock copolymers. Various physicochemical properties of mPEG-PLGA-PLL NPs, including morphology, size, surface charge, siRNA encapsulation efficiency, and in vitro release profile of siRNA from NPs, were characterized by scanning electron microscope, particle size and zeta potential analyzer, and high performance liquid chromatography. The levels of siRNA uptake and targeted gene inhibition were detected in human lung cancer SPC-A1-GFP cells stably expressing green fluorescent protein. Examination of the cultured SPC-A1-GFP cells with fluorescent microscope and flow cytometry showed NPs loading Cy3-labeled siRNA had much higher intracellular siRNA delivery efficiencies than siRNA alone and Lipofectamine-siRNA complexes. The gene silencing efficiency of mPEG-PLGA-PLL NPs was higher than that of commercially available transfecting agent Lipofectamine while showing no cytotoxicity. Thus, the current study demonstrates that biodegradable NPs of mPEG-PLGA-PLL triblock copolymers can be potentially applied as novel non-viral vectors for improving siRNA delivery and gene silencing.
Keywords: gene silencing; nanoparticles; PLGA; PLL; siRNA delivery; GFP

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Cite This Article

MDPI and ACS Style

Du, J.; Sun, Y.; Shi, Q.-S.; Liu, P.-F.; Zhu, M.-J.; Wang, C.-H.; Du, L.-F.; Duan, Y.-R. Biodegradable Nanoparticles of mPEG-PLGA-PLL Triblock Copolymers as Novel Non-Viral Vectors for Improving siRNA Delivery and Gene Silencing. Int. J. Mol. Sci. 2012, 13, 516-533.

AMA Style

Du J, Sun Y, Shi Q-S, Liu P-F, Zhu M-J, Wang C-H, Du L-F, Duan Y-R. Biodegradable Nanoparticles of mPEG-PLGA-PLL Triblock Copolymers as Novel Non-Viral Vectors for Improving siRNA Delivery and Gene Silencing. International Journal of Molecular Sciences. 2012; 13(1):516-533.

Chicago/Turabian Style

Du, Jing; Sun, Ying; Shi, Qiu-Sheng; Liu, Pei-Feng; Zhu, Ming-Jie; Wang, Chun-Hui; Du, Lian-Fang; Duan, You-Rong. 2012. "Biodegradable Nanoparticles of mPEG-PLGA-PLL Triblock Copolymers as Novel Non-Viral Vectors for Improving siRNA Delivery and Gene Silencing." Int. J. Mol. Sci. 13, no. 1: 516-533.

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