Biodegradable cationic polyester as an efficient carrier for gene delivery to neonatal cardiomyocytes.
Viral-mediated gene delivery has been explored for the treatment and protection of cardiomyocytes, but so far there is only one report using cationic polymer for gene delivery to cardiomyocytes in spite of many advantages of polymer-mediated gene delivery. In this study, a cationic poly(beta-amino ester) (PDMA) with a degradable backbone and cleavable side chains was synthesized by Michael addition reaction. The toxicity of PDMA to neonatal mouse cardiomyocytes (NMCMs) was significantly lower than that of polyethyleneimine (PEI). PDMA formed stable polyplexes with pEGFP. The dissociation of the polyplexes could be triggered by PDMA degradation, and the dissociation time was tunable via the polymer/pEGFP ratio. In vitro transfection showed that PDMA was an effective and low toxic gene delivery carrier for NMCMs. The PDMA/pEGFP polyplexes transfected EGFP gene to NMCMs with about 28% efficiency and caused little death. In contrast, a significant portion of cardiomyocytes cultured with PEI/pEGFP died.
Xu
Peisheng
P
Soft Materials Laboratory, Department of Chemical and Petroleum Engineering, University of Wyoming, Laramie, Wyoming 82071, USA.
Li
Shi-Yan
SY
Li
Qun
Q
Ren
Jun
J
Van Kirk
Edward A
EA
Murdoch
William J
WJ
Radosz
Maciej
M
Shen
Youqing
Y
D000178:Acrylamides / Q000138:chemical synthesis / Q000378:metabolism* / Q000493:pharmacokinetics / Q000633:toxicity; D000818:Animals; D000831:Animals, Newborn / Q000235:genetics; D001672:Biocompatible Materials / Q000008:administration & dosage / Q000138:chemical synthesis*; D004247:DNA / Q000378:metabolism; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors / Q000737:chemistry*; D051379:Mice; D032383:Myocytes, Cardiac / Q000737:chemistry*; D014162:Transfection / Q000379:methods*
D000178:Acrylamides; D001672:Biocompatible Materials; C429790:poly(N,N-dimethylacrylamide); D004247:DNA