Supramolecular host-guest polycationic gene delivery system based on poly(cyclodextrin) and azobenzene-terminated polycations

Supramolecular host-guest polycationic gene delivery system based on poly(cyclodextrin) and azobenzene-terminated polycations
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基于聚环糊精和偶氮苯封端聚阳离子的超分子主客体聚阳离子基因传递系统

DOI:
10.1016/j.colsurfb.2016.07.028
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发表时间:
2016
影响因子:
5.8
通讯作者:
Jiang Xulin
Jiang Xulin
中科院分区:
工程技术2区
文献类型:
--
作者:
Jiang Qimin;Zhang Yunti;Zhuo Renxi;Jiang Xulin

文献摘要

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本文介绍了基于聚β-环糊精(PCD)和偶氮苯封端的聚阳离子的超分子主客体基因传递系统。以甲基丙烯酸二甲氨基乙酯(DMAEMA)为单体,通过原子转移自由基聚合(ATRP)合成了端偶氮苯直链(Az-LPDM)和支链(Az-BPDM)阳离子聚合物。紫外可见光谱和核磁共振谱分析证实了偶氮苯封端的聚阳离子Az-LPDM和Az-BPDM与PCD形成的超分子聚阳离子的形成和光敏行为。PCD/Az-BPDM/DNA和PCD/Az-LPDM/DNA超分子复合物的大小和阳性率均低于无PCD的复合物。体外实验表明,与无PCD的偶氮苯端聚阳离子/DNA复合物相比,光敏超分子聚阳离子复合物(PCD/Az-LPDM/DNA和PCD/Az-BPDM/DNA)具有更高的细胞摄取、更高的转染效率和更低的细胞毒性。支化的聚阳离子复合物比线性的聚阳离子复合物具有更高的转染效率。此外,紫外光照射后,光敏超分子复合物的转染效率提高,这是由于更多的DNA被递送并释放到细胞核内。因此,这种含有偶氮苯封端的支化阳离子聚合物和PCD的光响应性超分子主客体系统是一种很有前途的基因载体。
This article describes the supramolecular host-guest polycationic gene delivery system based on poly(β-cyclodextrin) (PCD) and azobenzene-terminated polycations. The azobenzene-terminated linear (Az-LPDM) and branched (Az-BPDM) cationic polymers were synthesized by atom transfer radical polymerization (ATRP) of 2-dimethylamino ethyl methacrylate (DMAEMA). The formation and photosensitive behavior of the supramolecular polycations of azobenzene-terminated polycations Az-LPDM and Az-BPDM with PCD were confirmed by UV–vis and NMR analysis. The supramolecular PCD/Az-BPDM/DNA and PCD/Az-LPDM/DNA polyplexes showed smaller size and were less positive than those of their corresponding polyplexes without PCD. Moreover, the UV irradiation may promote release of DNA from the photosensitive supramolecular polyplexes due to dissociation of supramoelcular polyplexes.In vitroexperiments revealed that the photosensitive supramolecular polycationic polyplexes (PCD/Az-LPDM/DNA and PCD/Az-BPDM/DNA) exhibited enhancement of cellular uptake, higher transfection efficiency, and lower cytoxicity compared to the azobenzene-terminated polycation/DNA polyplexes in the absence of PCD. Branched polycationic polyplexes showed higher transfection efficiency than its linear polycationic polyplexes. Furthermore, after UV irradiation, the transfection efficiency of photosensitive supramolecular polyplexes was improved resulting from more DNAs delivered and released inside of the cell nuclei. Thus this photoresponsive supramolecular host-guest system containing azobenzene-terminated branched cationic polymers and PCD is a promising gene vector.