Biodegradable nanoparticles of mPEG-PLGA-PLL triblock copolymers as novel non-viral vectors for improving siRNA delivery and gene silencing.
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.
Department of Ultrasound, Shanghai First People's Hospital Affiliated to Shanghai Jiaotong University School of Medicine, 85 Wu Jin Road, Shanghai 200080, China.
Jing
J
Du
Cancer Institute of Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine, 2200 Xie Tu Road, Shanghai 200032, China.
Ying
Y
Sun
Department of Ultrasound, Shanghai First People's Hospital Affiliated to Shanghai Jiaotong University School of Medicine, 85 Wu Jin Road, Shanghai 200080, China.
Qiu-Sheng
QS
Shi
Cancer Institute of Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine, 2200 Xie Tu Road, Shanghai 200032, China.
Pei-Feng
PF
Liu
Cancer Institute of Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine, 2200 Xie Tu Road, Shanghai 200032, China.
Ming-Jie
MJ
Zhu
Sino-American United Biotechnology Institute Co., Ltd, 15 Zhong Jiang Road, Shanghai 200032, China.
Chun-Hui
CH
Wang
Department of Ultrasound, Shanghai First People's Hospital Affiliated to Shanghai Jiaotong University School of Medicine, 85 Wu Jin Road, Shanghai 200080, China.
Lian-Fang
LF
Du
Cancer Institute of Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine, 2200 Xie Tu Road, Shanghai 200032, China.
You-Rong
YR
Duan
D001672:Biocompatible Materials / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity; D002232:Carbocyanines / Q000737:chemistry; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004337:Drug Carriers / Q000737:chemistry; D006801:Humans; D008055:Lipids / Q000737:chemistry; D008856:Microscopy, Fluorescence; D053758:Nanoparticles / Q000737:chemistry / Q000378:metabolism* / Q000633:toxicity; D010316:Particle Size; D011091:Polyesters; D011092:Polyethylene Glycols / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity; D011098:Polyglactin 910 / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
D001672:Biocompatible Materials; D002232:Carbocyanines; D004337:Drug Carriers; D008055:Lipids; C086724:Lipofectamine; D011091:Polyesters; D034741:RNA, Small Interfering; C089187:cyanine dye 3; C558447:methoxypolyethyleneglycol-poly(lactic-co-glycolic acid); D011098:Polyglactin 910; D011092:Polyethylene Glycols