Synthesis of Biodegradable Cross-Linked Poly(beta-amino ester) for Gene Delivery and Its Modification,Inducing Enhanced Transfection Efficiency and Stepwise Degradation

摘要

Biodegradable cross-linked poly(beta-amino ester) (CLPAE) was synthesized by Michael addition of pentaerythritol triacrylate and N,N-dimethylethylenediamine and modified with aminohexanoic acid and lysine to CLPAE-Ahx and CLPAE-Lys,respectively,for a gene delivery system.They could self-assemble with plasmid DNA,forming nanosized polyplexes,and CLPAE-Ahx polyplex released plasmid DNA slowly during a week through stepwise degradation.The polymers showed minimal cytotoxicity on 293 cells due to their biodegradability and biocompatibility.Transfection efficiencies of CLPAE-Ahx and CLPAE-Lys were comparable to that of PEI in 293 cells and C2C12 cells.Additionally,high transfection of CLPAE-Ahx on primary rat aorta vascular smooth muscle cells (SMC) and primary mouse embryonic fibroblast cells (MEF) shows a potential for a gene delivery system on primary cells,restenosis treatment of human SMC,and MEF cell function research.In conclusion,CLPAE-Ahx could be used as a nontoxic and highly efficient gene delivery system.