A pH-Responsive Detachable PEG Shielding Strategy for Gene Delivery System in Cancer Therapy

被引：125

作者：

Guan, Xiuwen ^{[1
,2
]}

Guo, Zhaopei ^{[1
]}

Wang, Tinghong ^{[3
]}

Lin, Lin ^{[1
]}

Chen, Jie ^{[1
]}

Tian, Huayu ^{[1
]}

Chen, Xuesi ^{[1
]}

机构：

[1] Chinese Acad Sci, Changchun Inst Appl Chem, Key Lab Polymer Ecomat, Changchun 130022, Peoples R China

[2] Univ Chinese Acad Sci, Beijing 100049, Peoples R China

[3] Changchun Chaoyang Peoples Hosp, Changchun 130022, Peoples R China

来源：

BIOMACROMOLECULES | 2017年 / 18卷 / 04期

基金：

中国国家自然科学基金;

关键词：

BLOCK-COPOLYMERS; CELLULAR UPTAKE; SIRNA DELIVERY; IN-VIVO; NANOPARTICLES; PEGYLATION; POLYPLEXES; POLYETHYLENIMINE; TRAFFICKING; DRUG;

D O I：

10.1021/acs.biomac.7b00080

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

In this study, a pH-responsive detachable polyethylene glycol (PEG) shielding strategy was designed for gene delivery in cancer therapy. Polyethylenimine/DNA complex (PEI/DNA) was in situ shielded by aldehyde group-modified PEG derivatives. The aldehyde groups of PEG could react with the amino groups of PEI by Schiff base reaction. The Schiff base bond was stable in neutral pH but labile in slightly acidic pH, which made the PEG sheddable in tumors. PEG-coated nanoparticles (NPs) had distinct advantages compared to their mPEG counterpart, possessing decreased zeta potential, more compressed size, and enhanced stability. PEG/PEI/DNA NPs showed not only high tumor cell uptake and transfection efficiency in vitro but also efficient accumulation and gene expression in solid tumors in vivo. This pH-responsive detachable PEG shielding system has the potential to be applied to other polycationic nanoparticles that contain amino groups on their surfaces, which will have broad prospects in cancer therapy.

引用

页码：1342 / 1349

页数：8

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