Zhang Rujing, Zheng Nan, Song Ziyuan, Yin Lichen, Cheng Jianjun
Department of Materials Science and Engineering, University of Illinois at Urbana-Champaign, 1304 W Green Street, Urbana, IL 61801, USA.
Department of Materials Science and Engineering, University of Illinois at Urbana-Champaign, 1304 W Green Street, Urbana, IL 61801, USA.
Biomaterials. 2014 Mar;35(10):3443-54. doi: 10.1016/j.biomaterials.2013.12.097. Epub 2014 Jan 15.
The rational design of effective and safe non-viral gene vectors is largely dependent on the understanding of the structure-property relationship. We herein report the design of a new series of cationic, α-helical polypeptides with different side charged groups (amine and guanidine) and hydrophobicity, and mechanistically unraveled the effect of polypeptide structure on the gene delivery capability. Guanidine-containing polypeptides displayed superior membrane activities to their amine-containing analogues via the pore formation mechanism, and thus possessed notably higher transfection efficiencies. Elongating the hydrophobic side chain also potentiated the membrane activities of the polypeptides, while at the meantime caused higher cytotoxicities. Upon an optimal balance between membrane activity and cytotoxicity, maximal transfection efficiency was achieved which outperformed commercial reagent Lipofectamine™ 2000 (LPF2000) by 3-6 folds. This study thus provides mechanistic insights into the rational design of non-viral gene delivery vectors, and the best-performing materials identified also serve as a promising addition to the existing systems.
有效且安全的非病毒基因载体的合理设计很大程度上依赖于对结构-性质关系的理解。我们在此报告了一系列新的阳离子α-螺旋多肽的设计，这些多肽具有不同的带侧电荷基团（胺基和胍基）和疏水性，并从机制上揭示了多肽结构对基因递送能力的影响。含胍基的多肽通过孔形成机制表现出比其含胺基类似物更高的膜活性，因此具有显著更高的转染效率。延长疏水侧链也增强了多肽的膜活性，但同时导致更高的细胞毒性。在膜活性和细胞毒性之间达到最佳平衡时，实现了最大转染效率，其比市售试剂Lipofectamine™ 2000（LPF2000）高出3至6倍。因此，本研究为非病毒基因递送载体的合理设计提供了机制见解，所鉴定的性能最佳的材料也有望成为现有系统的补充。
