首页|Improving gene transfection efficiency of highly branched poly(β-amino ester)s through the in-situ conversion of inactive terminal groups

Improving gene transfection efficiency of highly branched poly(β-amino ester)s through the in-situ conversion of inactive terminal groups

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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.

Gene therapyGene delivery vectorHighly branched poly(β-amino ester)sTerminal groupsEpithelial cells

Zhili Li、Qijun Wo、Dongdong Huang、Dezhong Zhou、Lei Guo、Yeqing Mao

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Department of Urology,The First Affiliated Hospital,College of Medicine,Zhejiang University,Hangzhou 310000,China

School of Chemical Engineering and Technology,Xi'an Jiaotong University,Xi'an 710049,China

Urology & Nephrology Center,Department of Urology,Zhejiang Provincial People's Hospital(Affiliated People's Hospital),Hangzhou Medical College,Hangzhou 310014,China

Key Laboratory of Endocrine Gland Diseases of Zhejiang Province,Hangzhou 310014,China

Pooling Institute of Translational Medicine,Hangzhou 311100,China

School of Chemical Engineering and Technology,Xi'an Jiaotong University,Xi'an,710049,China

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2024

10.1016/j.cclet.2024.109737

中国化学快报(英文版)
中国化学会

中国化学快报(英文版)

CSTPCD
影响因子：0.771
ISSN：1001-8417
年,卷(期)：2024.35(8)