Receptor-mediated, tumor-targeted gene delivery using folate-terminated polyrotaxanes.
Receptor-mediated, tumor-targeted gene delivery using folate-terminated polyrotaxanes.
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DOI：
10.1021/mp200315c
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发表时间：
2012-04
影响因子：
4.9
通讯作者：
Yi Zhou;He Wang;Chengxi Wang;Yue-shan Li;Wenfeng Lu;Shui-fang Chen;Jiandong Luo;Yongnan Jiang;Jian-hai Chen
中科院分区：
文献类型：
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作者：
Yi Zhou;He Wang;Chengxi Wang;Yue-shan Li;Wenfeng Lu;Shui-fang Chen;Jiandong Luo;Yongnan Jiang;Jian-hai Chen
安全有效的基因递送对于基因治疗的成功至关重要。我们合成并表征了一种新型非病毒基因传递系统，其中叶酸（FA）分子作为阳离子聚轮烷（PR）的阻断剂，该阳离子聚轮烷由聚乙烯亚胺（PEI）（600）接枝的α-环糊精环在聚乙二醇上线性化形成FA封端的PR-PEI（600）（FPP）。 FPP 靶细胞的 FA 末端帽表面富含 FA 受体 (FR)，这是肿瘤细胞的共同特征。 FPP的结构通过(1)H核磁共振((1)H NMR)进行表征。递送颗粒由摩尔比为 1:17:86.7 化学键合的 PEG (4000)、α-环糊精 (CD) 和 PEI (600 Da) 组成，并使用动态光散射测量 FPP/pDNA 复合物的粒径和 zeta 电位。 FPP/pDNA表现出较低的细胞毒性、对FR的强特异性以及与报告基因在体外和体内将DNA递送至靶细胞的高效率。此外，与其他递送系统（例如PEI-25K）相比，FPP/DNA复合物在裸鼠中表现出增强的抗肿瘤作用。总之，这些结果表明 FPP 可能对基因治疗有用。
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 α-cyclodextrin rings linearized on polyethylene glycol to form FA-terminated PR-PEI(600) (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 (1)H nuclear magnetic resonance ((1)H NMR). The delivery particle was composed of chemically bonded PEG (4000), α-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.