Enhancing the Gene Transfection of Poly(ß-amino ester)/DNA Polyplexes by Modular Manipulation of Amphiphilicity

被引：12

作者：

Shi, Jiahao ^{[1
]}

Zhang, Yuhe ^{[1
]}

Ma, Bin ^{[1
]}

Yong, Haiyang ^{[1
]}

Che, Delu ^{[3
]}

Pan, Chaolan ^{[2
]}

He, Wei ^{[2
]}

Zhou, Dezhong ^{[1
]}

Li, Ming ^{[2
]}

机构：

[1] Xi An Jiao Tong Univ, Sch Chem Engn & Technol, Xian 710049, Peoples R China

[2] Fudan Univ, Childrens Hosp, Natl Childrens Med Ctr, Dept Dermatol, Shanghai 201102, Peoples R China

[3] Xi An Jiao Tong Univ, Hosp 2, Dept Dermatol, Xian 710061, Peoples R China

来源：

ACS APPLIED MATERIALS & INTERFACES | 2023年 / 15卷 / 36期

基金：

中国国家自然科学基金;

关键词：

gene transfection; poly(& beta; -amino ester)s; modular strategy; amphiphilicity; transfectionactivity; POLY(BETA-AMINO ESTERS); MESSENGER-RNA; DELIVERY; NANOPARTICLES;

D O I：

10.1021/acsami.3c03802

中图分类号：

TB3 [工程材料学];

学科分类号：

0805 ; 080502 ;

摘要：

Poly(ss-amino ester)s (PAEs) have been widely developed for gene delivery, and hydrophobic modification can further enhance their gene transfection efficiency. However, systematic manipulation of amphiphilicity of PAEs through copolymerization with hydrophobic monomers is time-consuming and, to some extent, uncontrollable. Here, a modular strategy is developed to manipulate the amphiphilicity of the PAE/DNA polyplexes. A hydrophobic polymer (DD-C12-122) and a hydrophilic polymer (DD-90-122) are synthesized separately and used as a hydrophobic module and a hydrophilic module, respectively. The amphiphilicity of polyplexes could be manipulated by changing the ratio of the hydrophobic module and hydrophilic module. Using the modular strategy, the PAE/DNA polyplexes with the highest gene transfection efficiency and safety profile as well as possible mechanisms are identified. The modular strategy provides a novel way to engineer the hydrophobicity of PAEs to improve their gene transfection and can be easily generalized and potentially extended to other polymeric gene delivery systems.

引用

页码：42130 / 42138

页数：9

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