A Cell-Specific Poly(ethylene glycol) Derivative with a Wheat-like Structure for Efficient Gene Delivery

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• 作者：Hanmei Li ; Xun Sun ; Dong Zhao ; Zhirong Zhang
• 刊名：Molecular Pharmaceutics
• 出版年：2012
• 出版时间：November 5, 2012
• 年：2012
• 卷：9
• 期：11
• 页码：2974-2985
• 全文大小：592K
• 年卷期：v.9,no.11(November 5, 2012)
• ISSN：1543-8392

文摘

A novel anionic PEG derivative with a wheat-like structure, PEG-poly(AGE-Suc), was synthesized. The spikelet part of this polymer consisting of 9.3 pairs of carboxylic acid side chains was conjugated at one end of the PEG chain. The neutral linear PEG₁₅₈₀ was designed as the stalk part to improve the biocompatibility of the vectors. The obtained polymer PEG-poly(AGE-Suc) was further modified by folate (FA) at the distal end to achieve the cell-specific targeting. It was confirmed that the negatively charged FA-PEG-poly(AGE-Suc) could coat the positively charged PEI 25K/DNA complex and form a ternary complex by electrostatic interaction. The addition of FA-PEG-poly(AGE-Suc) could change the positive charge of PEI 25K/DNA complexes to negative with no influence on the diameter. The ternary complex with the coat of FA-PEG-poly(AGE-Suc) could effectively condense DNA and protect it from degradation by DNase I. The nonspecific interaction between PEI 25K/DNA complexes and blood components was also significantly reduced by the addition of anionic PEG. The ternary complex PEI 25K/DNA/FA-PEG-poly(AGE-Suc) exhibited a 12-fold higher transfection efficiency on 293T cells compared to PEI 25K/DNA in the serum-containing medium. The competitive folate inhibition assay demonstrated that the higher transfection efficiency of PEI 25K/DNA/FA-PEG-poly(AGE-Suc) was attributed to the folate molecule conjugated to the distal end of FA-PEG-poly(AGE-Suc). The ternary complex PEI 25k/DNA/FA-PEG-poly(AGE-Suc) with low side effects and high transfection efficiency may be a novel effective gene delivery system.

Keywords:

anionic PEG derivative; folate; PEI; ternary complex; livery+system&qsSearchArea=searchText">gene delivery system