Targeted Gene Delivery Mediated by Folate-polyethylenimine-block-poly(ethylene glycol) with Receptor Selectivity

被引:74
作者
Cheng, Han [1 ]
Zhu, Jing-Ling [1 ]
Zeng, Xuan [1 ]
Jing, Yue [1 ]
Zhang, Xian-Zheng [1 ]
Zhuo, Ren-Xi [1 ]
机构
[1] Wuhan Univ, Dept Chem, Minist Educ, Key Lab Biomed Polymers, Wuhan 430072, Peoples R China
基金
中国国家自然科学基金;
关键词
CHITOSAN-DNA NANOPARTICLES; POLYION COMPLEX MICELLES; LOW-MOLECULAR-WEIGHT; PHYSICOCHEMICAL PROPERTIES; TRANSFECTION EFFICIENCY; ADENOASSOCIATED VIRUS; CATIONIC POLYMERS; NONVIRAL VECTOR; BLOCK-COPOLYMER; THERAPY;
D O I
10.1021/bc8004057
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
The folate receptor (FR) is a tumor marker overexpressed in large numbers of cancer cells. Folic acid has high affinity to the FR and retains its binding affinity upon derivatization via its gamma-carboxyl. Therefore, in this article, folate-polyethylenimine-block-poly(ethylene glycol) (FOL-PEI-b-PEG) was designed for specific receptor targeted gene delivery. Physicochemical characterizations of resulting FOL-PEI-b-PEG/DNA complexes in terms of agarose gel electrophoresis, particle size, and zeta potential measurements were investigated. The results indicated that FOL-PEI-b-PEG was able to condense plasmid DNA tightly with a suitable particle size. The cytotoxicity study indicated that the copolymer exhibited less toxicity in comparison with that of 25 kDa PEI. Luciferase assay and green fluorescent protein (GFP) detections were also used to confirm that FOL-PEI-b-PEG could be an effective gene vector. Importantly, transfection efficiency of FOL-PEI-b-PEG with free folic acid was much lower than that of the copolymer without free folic acid on FR-positive HeLa cells, suggesting that FOL-PEI-b-PEG has great potential as a targeting gene vector.
引用
收藏
页码:481 / 487
页数:7
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