A family of cationic polyamides for in vitro and in vivo gene transfection.
The purpose of this study is to develop biodegradable cationic polyamides for non-viral gene delivery and elucidate their structural effects on gene transfection activity. To this end, a group of novel cationic polyamides were synthesized by polycondensation reaction between different di-p-nitrophenyl esters and tertiary amine-containing primary diamines. These linear polyamides have flexible alkylene group (ethylene or propylene), protonable amino group and bioreducible disulfide linkage in the polyamide main chain. The alkylene group and disulfide linkage in these polyamides have a distinct effect on their gene delivery properties including buffering capacity, gene binding ability and intracellular gene release profile. Those cationic polyamides containing disulfide linkage and 1,4-bis(3-aminopropyl)piperazine (BAP) residue exhibited high buffering capacity (endosomal escape ability), high gene binding ability, and intracellular gene release ability, thus inducing fast gene nucleus translocation and robust gene transfection in vitro against different cell lines and rat bone marrow mesenchymal stem cells. Moreover, the transfection efficiencies in vitro were comparable or higher than those of 25 kDa branched polyethylenimine and Lipofectamine 2000 transfection agent as positive controls. These cationic polyamides and their polyplexes were of low cytotoxicity when an optimal transfection efficacy was achieved. In vivo transfection tests showed that bioreducible BAP-based polyamides were applicable for intravenous gene delivery in a mouse model, leading to higher level of transgene expression in the liver as compared to 22 kDa linear polyethylenimine as a positive control. These cationic polyamides provide a useful platform to elucidate the relationship between chemical functionalities and gene transfection activity.
Shanghai East Hospital, The Institute for Biomedical Engineering and Nanoscience, Tongji University School of Medicine, Tongji University, Shanghai 200092, People's Republic of China.
Chengnan
C
Zhang
Institute of Nanochemistry and Nanobiology, Shanghai University, Shanghai 200444, People's Republic of China.
Rong
R
Jin
Shanghai East Hospital, The Institute for Biomedical Engineering and Nanoscience, Tongji University School of Medicine, Tongji University, Shanghai 200092, People's Republic of China.
Peng
P
Zhao
Shanghai East Hospital, The Institute for Biomedical Engineering and Nanoscience, Tongji University School of Medicine, Tongji University, Shanghai 200092, People's Republic of China. Electronic address: chaolin@tongji.edu.cn.
Chao
C
Lin
D000143:Acids / Q000737:chemistry; D000818:Animals; D002412:Cations / Q000737:chemistry*; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D004705:Endocytosis / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D051379:Mice; D009757:Nylons / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D014162:Transfection / Q000379:methods*; D019076:Transgenes
D000143:Acids; D002412:Cations; D009757:Nylons
Disulfide; Polyamide; Polycondensation; Stem cell; Transfection