Highly branched poly(β-amino ester)s(HPAEs)have emerged as a safe and efficient type of non-viral gene delivery vectors.However,the presence of inactive terminal secondary amine groups compromises their gene transfec...Highly branched poly(β-amino ester)s(HPAEs)have emerged as a safe and efficient type of non-viral gene delivery vectors.However,the presence of inactive terminal secondary amine groups compromises their gene transfection capability.In this study,HPAEs with similar topological structures and chemical compositions but varying numbers of terminal secondary 4-amino-1-butanol(S4)and secondary/tertiary 3-morpholinopropylamine(MPA)groups were synthesized.The results demonstrate that an increased number of secondary/tertiary MPA groups in-situ significantly enhances the DNA binding capability of HPAEs,leading to the formation of smaller HPAE/DNA polyplexes with higher zeta potential,ultimately resulting in superior gene transfection efficiency in bladder epithelial cells.This study establishes a sim-ple yet effective strategy to maximize the gene transfection potency of HPAEs by converting the inactive terminal groups in-situ without the need for complex modifications to their topological structure and chemical composition.展开更多
基金funded by the National Natural Science Foundation of China(NSFC,No.51903202)the Key R&D Program of Shaanxi Province(No.2020GXLH-Y-016)+2 种基金the Natural Science Foundation of Shaanxi Province(No.2020JM-055)the Fundamental Re-search Funds for the Central Universities(No.xtr042019020)the Young Talents Support Plan of Xi’an Jiaotong University(No.HG6J002).
文摘Highly branched poly(β-amino ester)s(HPAEs)have emerged as a safe and efficient type of non-viral gene delivery vectors.However,the presence of inactive terminal secondary amine groups compromises their gene transfection capability.In this study,HPAEs with similar topological structures and chemical compositions but varying numbers of terminal secondary 4-amino-1-butanol(S4)and secondary/tertiary 3-morpholinopropylamine(MPA)groups were synthesized.The results demonstrate that an increased number of secondary/tertiary MPA groups in-situ significantly enhances the DNA binding capability of HPAEs,leading to the formation of smaller HPAE/DNA polyplexes with higher zeta potential,ultimately resulting in superior gene transfection efficiency in bladder epithelial cells.This study establishes a sim-ple yet effective strategy to maximize the gene transfection potency of HPAEs by converting the inactive terminal groups in-situ without the need for complex modifications to their topological structure and chemical composition.
