Receptor-Mediated, Tumor-Targeted Gene Delivery Using Folate-Terminated Polyrotaxanes

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• 作者：Yi Zhou ; He Wang ; Chengxi Wang ; Yueshan Li ; Wenfeng Lu ; Shuifang Chen ; Jiandong Luo ; Yongnan Jiang ; Jianhai Chen
• 刊名：Molecular Pharmaceutics
• 出版年：2012
• 出版时间：May 7, 2012
• 年：2012
• 卷：9
• 期：5
• 页码：1067-1076
• 全文大小：480K
• 年卷期：v.9,no.5(May 7, 2012)
• ISSN：1543-8392

文摘

Safe and effective gene delivery is essential to the success of gene therapy. We synthesized and characterized a novel nonviral gene delivery system in which folate (FA) molecules were functioned as blockers on cationic polyrotaxanes (PR) composed of poly(ethylenimine) (PEI)₆₀₀-grafted 伪-cyclodextrin rings linearized on polyethylene glycol to form FA-terminated PR-PEI₆₀₀ (FPP). The FA terminal caps of FPP target cell surfaces abundant in FA receptor (FR), a common feature of tumor cells. The structure of FPP was characterized by using ¹H nuclear magnetic resonance (¹H NMR). The delivery particle was composed of chemically bonded PEG (4000), 伪-cyclodextrins (CD), and PEI (600 Da) at a molar ratio of 1:17:86.7, and the particle size and zeta potential of FPP/pDNA polyplexes were measured using dynamic light scattering. FPP/pDNA exhibited a lower cytotoxicity, strong specificity to FR, and high efficiency of delivering DNA to target cells in vitro and in vivo with the reporter genes. Furthermore, the FPP/DNA complex showed an enhanced antitumor effect in the nude mice compared with other delivery systems, such as PEI-25K. Together, these results suggest that FPP may be useful for gene therapy.

Keywords:

poly(ethylenimine); supramolecule; cyclodextrin; folate receptor targeting; gene carrier