Citation: Chenfei Wang, Litao Sun, Qiuxia Li, Zhili Li, Chengyuan Xu, Xinyue Zhang, Jianjun Shi, Hao Zhou, Wenxin Wang, Dezhong Zhou. Highly branched poly(β-amino ester)s with narrow molecular weight distribution: Fractionation and gene transfection activity[J]. Chinese Chemical Letters, ;2023, 34(3): 107627. doi: 10.1016/j.cclet.2022.06.050 shu

Highly branched poly(β-amino ester)s with narrow molecular weight distribution: Fractionation and gene transfection activity

Chenfei Wang ^a ,
Litao Sun ^a ,
Qiuxia Li ^a ,
Zhili Li ^a ,
Chengyuan Xu ^a ,
Xinyue Zhang ^d ,
Jianjun Shi ^{a, b, *,} ,
Hao Zhou ^{c, *,} ,
Wenxin Wang ^e ,
Dezhong Zhou ^{a, *,}

a.
School of Chemical Engineering and Technology, Xi'an Jiaotong University, Xi'an 710049, China
b.
Key Laboratory of Water Pollution Treatment & Resource Reuse, Hainan Normal University, Haikou 571158, China
c.
State Key Laboratory of Medicinal Chemical Biology, Tianjin Key Laboratory of Protein Science, and College of Life Sciences, Nankai University, Tianjin 300071, China
d.
Department of Dermatology, The Second Hospital Affiliated to Xi'an Jiaotong University, Xi'an 710061, China
e.
Charles Institute of Dermatology, School of Medicine, University College Dublin, Dublin 4, Ireland

stone0801@163.com

haozhou@nankai.edu.cn

dezhong.zhou@xjtu.edu.cn

Received Date: 26 January 2022
Revised Date: 15 June 2022
Accepted Date: 20 June 2022
Available Online: 22 June 2022

Figures(5)

Highly branched poly(β-amino ester)s (HPAEs) have shown their great promise in gene delivery. However, their broad molecular weight distribution (MWD) poses an additional challenge to the mechanistic understanding of the influence of molecular weight (MW) on their gene transfection activity. Using a stepwise precipitation strategy, HPAEs were fractionated. It is shown that MW has a significant effect on the transfection activity and cytotoxicity of HPAEs. The intermediate MW mediates higher transfection efficiency while maintaining high cell viability. Mechanistic studies show that the intermediate MW confers stronger DNA binding affinity to HPAEs, leading to the formulation of polyplexes with a relatively smaller size and more positive zeta potential. This study not only suggests a simple strategy to fractionate HPAEs with narrow MWD but also provides new insights into understanding the structure-property relationship, which would facilitate the clinical translation of HPAEs in gene therapy.
- Gene transfection,
- Non-viral vector,
- Highly branched poly(β-amino ester)s,
- Fractionation,
- Transfection activity
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