Department of Materials and §Institute of Pharmaceutical Sciences, Department of Chemistry and Applied Biosciences, ETH-Zürich , CH-8093, Switzerland.
Biomacromolecules. 2014 May 12;15(5):1707-15. doi: 10.1021/bm5001197. Epub 2014 Apr 22.
In this study, we systematically explore the influence of the lipophilic group on the siRNA transfection properties of the polycationic-based delivery vectors. For this, a novel and modular synthetic strategy was developed for the preparation of polymers carrying a cationic site and a lipophilic group at each polymer repeat unit. These bifunctional polymers could form a complex with siRNA and deliver it to human colon carcinoma cells (HT-29-luc). In general, transfection capability increased with an increase in the chain length of the lipophilic moiety. The best transfection agent, a polymer containing ammonium groups and pentyl side chains, exhibited lower toxicity and higher transfection efficiency than branched and linear polyethylenimines (PEI). Moreover, as opposed to PEI, the transfection efficiency of polymer/siRNA complexes remained unchanged in the presence of bafilomycin A1, a proton pump inhibitor, suggesting that the present system did not rely on the "proton sponge" effect for siRNA delivery.
在这项研究中，我们系统地研究了亲脂基团对基于聚阳离子的递送载体转染 siRNA 性质的影响。为此，开发了一种新颖的模块化合成策略，用于制备在每个聚合物重复单元上带有阳离子和亲脂基团的聚合物。这些双功能聚合物可以与 siRNA 形成复合物并将其递送至人结肠癌细胞（HT-29-luc）。一般来说，转染能力随亲脂部分链长的增加而增加。最佳转染试剂是一种含有铵基团和戊基侧链的聚合物，其毒性低于支化和线性聚乙烯亚胺（PEI），转染效率更高。此外，与 PEI 不同，质子泵抑制剂巴弗洛霉素 A1 的存在并不改变聚合物/siRNA 复合物的转染效率，这表明该体系不依赖于“质子海绵”效应来递送 siRNA。
