A reducible polycationic gene vector derived from thiolated low molecular weight branched polyethyleneimine linked by 2-iminothiolane.
A reducible polycationic gene vector derived from thiolated low molecular weight branched polyethyleneimine linked by 2-iminothiolane.
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DOI：
10.1016/j.biomaterials.2010.08.079
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发表时间：
2011-02
期刊：
影响因子：
14
通讯作者：
Bae, You Han
中科院分区：
文献类型：
--
作者：
Kang, Han Chang;Kang, Ho-Jung;Bae, You Han
关键词：
为了提高高分子基因载体的转染效率和降低细胞毒性，以低分子量支链聚乙烯亚胺（bPEI）为原料，通过硫醇化和氧化反应合成了可还原聚阳离子（RPC）。RPC（RPC-bPEI 0. 8 kDa）分子量为5 kDa~80 kDa，最终产物保留了bPEI 0. 8 kDa原有质子缓冲能力的50%~70%。RPC-bPEI 0.8kDa的细胞毒性比高分子转染试剂的金标准bPEI 25 kDa低8~19倍。尽管bPEI 0. 8 kDa表现出较差的基因凝聚能力（在40的重量比（WR）下约为2 µm），但RPC-bPEI 0. 8 kDa在WR为2时有效地凝聚了质粒DNA（pDNA）。RPC-bPEI 0. 8 kDa/pDNA（WR ≥ 2）可形成100~200 nm大小的颗粒，表面带正电（20~35 mV）。此外，巯基/聚阴离子可通过断裂和离子交换作用引发RPC-bPEI 0. 8 kDa/pDNA的释放。RPC-bPEI 0. 8 kDa/pDNA的转染效率是bPEI 0. 8 kDa/pDNA的1200~1500倍，与bPEI 25 kDa/pDNA相当或上级（约7倍）。有趣的是，高分子量RPC-bPEI 0. 8 kDa/pDNA在细胞核中的分布高于低分子量RPC-bPEI 0. 8 kDa/pDNA。因此，本研究的结果表明RPC-bPEI 0. 8 kDa具有有效递送具有较低毒性水平的遗传物质的潜力。
To improve transfection efficiency and reduce the cytotoxicity of polymeric gene vectors, reducible polycations (RPC) were synthesized from low molecular weight (MW) branched polyethyleneimine (bPEI) via thiolation and oxidation. RPC (RPC-bPEI0.8kDa) possessed a MW of 5 kDa~80 kDa, and 50%~70% of the original proton buffering capacity of bPEI0.8kDa was preserved in the final product. The cytotoxicity of RPC-bPEI0.8kDa was 8~19 times less than that of the gold standard of polymeric transfection reagents, bPEI25kDa. Although bPEI0.8kDa exhibited poor gene condensing capacities (~2 µm at a weight ratio (WR) of 40), RPC-bPEI0.8kDa effectively condensed plasmid DNA (pDNA) at a WR of 2. Moreover, RPC-bPEI0.8kDa/pDNA (WR ≥ 2) formed 100~200 nm-sized particles with positively charged surfaces (20~35 mV). In addition, the results of the present study indicated that thiol/polyanions triggered the release of pDNA from RPC-bPEI0.8kDa/pDNA via the fragmentation of RPC-bPEI0.8kDa and ion-exchange. With negligible polyplex-mediated cytotoxicity, the transfection efficiencies of RPC-bPEI0.8kDa/pDNA were approximately 1200~1500-fold greater than that of bPEI0.8kDa/pDNA and were equivalent or superior (~7-fold) to that of bPEI25kDa/pDNA. Interestingly, the distribution of high MW RPC-bPEI0.8kDa/pDNA in the nucleus of the cell was higher than that of low MW RPC-bPEI0.8kDa/pDNA. Thus, the results of the present study suggest that RPC-bPEI0.8kDa has the potential to effectively deliver genetic materials with lower levels of toxicity.
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