title: Increase in transgene expression by pluronic L64-mediated endosomal/lysosomal escape through its membrane-disturbing action.
abstract: For efficient transgene delivery and expression, internalized nucleic acids should quickly escape from cellular endosomes and lysosomes to avoid enzymatic destruction and degradation. Here, we report a novel strategy for safe and efficient endosomal/lysosomal escape of transgenes mediated by Pluronic L64, a neutral amphiphilic triblock copolymer. L64 enhanced the permeability of biomembranes by structural disturbance and pore formation in a concentration- and time-dependent manner. When applied at optimal concentration, it rapidly reached the endosome/lysosome compartments, where it facilitated escape of the transfection complex from the compartments and dissociation of the complex. Therefore, when applied properly, L64 not only significantly increased polyethylenimine- and liposome-mediated transgene expression, but also decreased the cytotoxicity occasioned by transfection process. Our studies revealed the function and mechanism of neutral amphiphilic triblock copolymer as potent mediator for safe and efficient gene delivery.
authors: †Key Laboratory for Bio-Resource and Eco-Environment of Ministry Education, Key Laboratory for Animal Disease Prevention and Food Safety of Sichuan Province, College of Life Science, Sichuan University, Chengdu, Sichuan 610064, China.|‡National Engineering Research Center for Biomaterials, Sichuan University, Chengdu, Sichuan 610064, China.
authors: Jianlin
authors: J
authors: Chen
authors: †Key Laboratory for Bio-Resource and Eco-Environment of Ministry Education, Key Laboratory for Animal Disease Prevention and Food Safety of Sichuan Province, College of Life Science, Sichuan University, Chengdu, Sichuan 610064, China.|‡National Engineering Research Center for Biomaterials, Sichuan University, Chengdu, Sichuan 610064, China.
authors: Jing
authors: J
authors: Luo
authors: §College of Acupuncture and Massage, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan 610075, China.
authors: Ying
authors: Y
authors: Zhao
authors: ‡National Engineering Research Center for Biomaterials, Sichuan University, Chengdu, Sichuan 610064, China.
authors: Linyu
authors: L
authors: Pu
authors: §College of Acupuncture and Massage, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan 610075, China.
authors: Xuejing
authors: X
authors: Lu
authors: †Key Laboratory for Bio-Resource and Eco-Environment of Ministry Education, Key Laboratory for Animal Disease Prevention and Food Safety of Sichuan Province, College of Life Science, Sichuan University, Chengdu, Sichuan 610064, China.
authors: Rong
authors: R
authors: Gao
authors: ‡National Engineering Research Center for Biomaterials, Sichuan University, Chengdu, Sichuan 610064, China.
authors: Gang
authors: G
authors: Wang
authors: ‡National Engineering Research Center for Biomaterials, Sichuan University, Chengdu, Sichuan 610064, China.
authors: Zhongwei
authors: Z
authors: Gu
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000737:chemistry*; D011992:Endosomes / Q000737:chemistry*; D006367:HeLa Cells; D006801:Humans; D008247:Lysosomes / Q000737:chemistry; D008422:Materials Testing; D051379:Mice; D041681:NIH 3T3 Cells; D053769:Nanocapsules / Q000737:chemistry* / Q000648:ultrastructure; D010957:Plasmids / Q000008:administration & dosage / Q000737:chemistry / Q000235:genetics; D020442:Poloxamer / Q000737:chemistry*; D014162:Transfection / Q000379:methods*; D019076:Transgenes / Q000235:genetics*; D015854:Up-Regulation / Q000235:genetics
chemical_list: D053769:Nanocapsules; D020442:Poloxamer; C514452:pluronic L64
keywords: PluronicL64; amphiphilic triblock copolymer; biomembrane; endocytosis; endosomal/lysosomal escape; gene delivery