期刊
JOURNAL OF CONTROLLED RELEASE
卷 121, 期 1-2, 页码 38-48出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jconrel.2007.05.012
关键词
non-viral gene vector; block copolymer; polyplex micelle; spheroid
Polyplexes consisting of plasmid DNA and polycations have received much attention as promising vectors for gene transfer. For effective gene therapy, polycations with different polyamine structures in the side chain were developed to ensure their buffering capacity for endosomal escape, and their PEGylated block copolymers were developed to increase their stability and biocompatibility. The effects of the chemical structures of polycations and their PEGylation on transfection and cytotoxicity were elucidated by use of a three-dimensional multicellular tumor spheroid of human hepatoma HuH-7 cells. Various features of transfection with polyplex micelles, which have been hard to observe in conventional monolayer cultures, were revealed by the multicellular tumor spheroid (MCTS) model in terms of cytotoxicity and time-dependent behaviors of transfected gene expression under three-dimensional microenvironments. By using this system, the polyplex micelle from poly(ethylene glycol)-b-poly(N-substituted asparagine) copolymers having the N-(2-aminoethyl)-2-aminoethyl group in the side chain (PEG-b-P[Asp(DET)] polyplex micelle) was proved to achieve high transfection efficiencies as well as low cytotoxicity, both of which are critical properties for successful in vivo gene delivery. C) 2007 Elsevier B.V. All rights reserved.
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