Polyethylenimine-grafted polycarbonates as biodegradable polycations for gene delivery.
Polyethylenimine-grafted polycarbonates as biodegradable polycations for gene delivery.
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DOI：
10.1016/j.biomaterials.2009.05.053
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发表时间：
2009-09
期刊：
影响因子：
14
通讯作者：
Chang-Fang Wang;Yanwen Lin;Tao Jiang;F. He;R. Zhuo
中科院分区：
文献类型：
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作者：
Chang-Fang Wang;Yanwen Lin;Tao Jiang;F. He;R. Zhuo
聚阳离子作为一种非病毒载体越来越受到人们的关注。本文合成了聚乙烯亚胺（PEI）接枝聚碳酸酯（PMAC-g-PEIx）作为一种可生物降解的基因载体。以固定化猪胰脂肪酶（IPPL）为催化剂，本体法合成了主链聚合物聚（5-甲基-5-烯丙氧基羰基三亚甲基碳酸酯）（PMAC）。然后，PMAC的烯丙基环氧化产物PMAC-O进一步用低分子量的PEIx（x = 423、800和1800）改性。通过GPC-MALLS测量的PMAC-g-PEIx的MW分别为81，900、17，9900和200，600 g/mol，多分散性分别为1.2、1.4和1.7。PAMC-g-PEIx/DNA复合物可与pDNA形成带正电荷的纳米粒子（30-90 nm），三种PAMC-g-PEIx/DNA复合物的缓冲能力相似。体外实验表明，PAMC-g-PEIx对293 T细胞的细胞毒性明显低于PEI 25 K，转染效率明显高于PEI 25 K。此外，PMAC-g-PEI 1800的预孵育显示与DNA的结合能力减弱。PMAC-g-PEIx的生物降解性可以促进pDNA从聚合复合物中的有效释放并降低细胞毒性。这些结果表明，PMAC-g-PEIx是一种很有前途的非病毒生物降解载体的基因传递系统。
Polycations as one of non-viral vectors have gained increasing attentions. In this paper, polyethylenimine(PEI)-grafted polycarbonates (PMAC-g-PEIx) were synthesized as a kind of biodegradable polycations for gene delivery. Backbone polymer, poly(5-methyl-5-allyloxycarbonyl-trimethylene carbonate) (PMAC), was synthesized in bulk catalyzed by immobilized porcine pancreas lipase (IPPL). Then, PMAC–O, the allyl epoxidation product of PMAC, was further modified by PEIx with low molecular weight (x = 423, 800 and 1800). The MWs of PMAC-g-PEIx, measured by GPC–MALLS, were 81,900, 17,9900 and 200,600 g/mol with polydispersities of 1.2, 1.4 and 1.7, respectively. PMAC-g-PEIx could form positively charged nano-sized particles (30–90 nm) with pDNA, and all the three PAMC-g-PEIx/DNA polyplexes had similar buffer capabilities. In vitro experiments demonstrated that the PAMC-g-PEIx showed much low cytotoxicity and enhanced transfection efficiency could be found in comparison with PEI25K in 293T cells. Furthermore, pre-incubation of PMAC-g-PEI1800 showed a weakening binding capacity with DNA. The biodegradability of PMAC-g-PEIx can facilitate the efficient release of pDNA from polyplexes and reduce cell cytotoxicity. These results suggested that PMAC-g-PEIx would be a promising non-viral biodegradable vector for gene delivery system.