Transfection study using multicellular tumor spheroids for screening non-viral polymeric gene vectors with low cytotoxicity and high transfection efficiencies

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 PE...

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Veröffentlicht in:Journal of controlled release 2007-08, Vol.121 (1), p.38-48
Hauptverfasser: Han, Muri, Bae, Younsoo, Nishiyama, Nobuhiro, Miyata, Kanjiro, Oba, Makoto, Kataoka, Kazunori
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container_end_page 48
container_issue 1
container_start_page 38
container_title Journal of controlled release
container_volume 121
creator Han, Muri
Bae, Younsoo
Nishiyama, Nobuhiro
Miyata, Kanjiro
Oba, Makoto
Kataoka, Kazunori
description 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.
doi_str_mv 10.1016/j.jconrel.2007.05.012
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subjects Biocompatible Materials
Biological and medical sciences
Block copolymer
Carcinoma, Hepatocellular - pathology
Cell Line, Tumor
Cell Survival
Gene Expression
General pharmacology
Genes, Reporter
Genetic Vectors
Humans
Hydrogen-Ion Concentration
Liver Neoplasms - pathology
Luciferases - metabolism
Luminescent Measurements
Medical sciences
Micelles
Nanotechnology
Non-viral gene vector
Pharmaceutical technology. Pharmaceutical industry
Pharmacology. Drug treatments
Plasmids - genetics
Polyamines - chemistry
Polyethylene Glycols - chemistry
Polymers - chemical synthesis
Polymers - chemistry
Polyplex micelle
Spheroid
Spheroids, Cellular
Transfection - methods
title Transfection study using multicellular tumor spheroids for screening non-viral polymeric gene vectors with low cytotoxicity and high transfection efficiencies
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