Poly[(5-methyl-5-allyloxycarbonyl-trimethylene carbonate)-co-(5,5-dimethyl-trimethylene carbonate)] with Grafted Polyethylenimine as Biodegradable Polycations for Efficient Gene Delivery
Poly[(5-methyl-5-allyloxycarbonyl-trimethylene carbonate)-co-(5,5-dimethyl-trimethylene carbonate)] with Grafted Polyethylenimine as Biodegradable Polycations for Efficient Gene Delivery
复制标题
聚[(5-甲基-5-烯丙氧基羰基-三亚甲基碳酸酯)-共-(5,5-二甲基-三亚甲基碳酸酯)]与接枝聚乙烯亚胺作为可生物降解的聚阳离子用于高效基因递送
DOI：
10.1021/bm1008525
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发表时间：
2010-11-01
影响因子：
6.2
通讯作者：
Zhuo, Ren-Xi
中科院分区：
文献类型：
--
作者：
He, Feng;Wang, Chang-Fang;Zhuo, Ren-Xi
本文合成了聚碳酸酯接枝聚乙烯亚胺(PEI)的可生物降解聚阳离子作为非病毒载体或基因载体。用固定化猪胰脏脂肪酶(IPPL)催化5-甲基-5-烯丙氧基三亚甲基碳酸酯(MAC)与5，5-二甲基三亚甲基碳酸酯(DTC)的共聚反应。DTC摩尔分数X分别等于6.7、12.5和45.4。所得不同组成的共聚物(P(MAC-co-DTCx))经过额外的烯丙基环氧化，从而接枝到低相对分子质量的PEI1800上。GPC-MALS测得P(MAC-co-DTCx)-g-PEI的相对分子质量分别为219800、179100和51700克/摩尔，多分散度分别为1.5、1.4和1.2g/摩尔。对载体的理化性质进行了表征，并对载体的DNA载量进行了评价。P(MAC-co-DTCx)-g-PEI可与PDNA形成小于100 nm的纳米粒子。三种P(MAC-co-DTCx)-g-PEI/DNA复合体具有相似的缓冲能力，优于PE125K和PMAC-g-PEI。尽管DNA结合能力稍低，但在293T细胞中，PEI接枝的聚碳酸酯，尤其是P(MAC-co-DTC45.4)-g-PEI，表现出明显的低细胞毒性和比PEI25K更高的基因转染率。此外，P(MAC-co-DTC6.7)-g-PEI的预孵育显示出DNA结合能力的迅速减弱，而适当的载体降解速度有利于细胞摄取后PDNA从复合体中有效地释放，并降低细胞毒性。这项研究的结果证明了P(MAC-co-DTCx)-g-PEI共聚物在高效基因传递方面的前景。
In this paper, biodegradable polycations based on polycarbonates with grafted polyethylenimine (PEI) were synthesized as a nonviral vector or gene delivery. Immobilized porcine pancreas lipase (IPPL) was employed 19 perform the copolymerization of 5-methyl-5-allyloxy carbonyl-trimethylenecarbonate (MAC) with 5,5-dimethyl-trimethylene carbonate (DTC). The DTC molar percent X was equal to 6.7, 12.5, and 45.4, respectively. The resulting copolymers with different compositions (P(MAC-co-DTCx) underwent additional allyl epoxidation and thereby grafted by low molecular weight PEI1800. The MWs of P(MAC-co-DTCx)-g-PEI, measured by GPC-MALLS, were 219800, 179100, and 51700 g/mol with polydispersities of 1.5, 1.4, and 1.2, respectively. Physicochemical properties of these vectors were characterized and the DNA loading was evaluated. P(MAC-co-DTCx)-g-PEI could form nanosized particles (less than 100 nm) with pDNA. The three P(MAC-co-DTCx)-g-PEI/DNA polyplexes had similar buffer capabilities that were better than that of PE125K and PMAC-g-PEI. Despite a slightly lower DNA binding ability, the PEI-grafted polycarbonates, especially P(MAC-co-DTC45.4)-g-PEI, presented apparently low cytotoxicity and much higher gene transfection efficiency in comparison with PEI25K in 293T cells. Moreover, preincubation of P(MAC-co-DTC6.7)-g-PEI showed a quickly weakening DNA binding capacity, while a suitable degradation rate of vectors would facilitate the efficient release of pDNA from polyplexes after cellular uptake and also reduce cell cytotoxicity. The results of this study demonstrated the promise of P(MAC-co-DTCx)-g-PEI copolymers for efficient gene delivery.