为了获得更高的转染效率和更低的毒性,本研究合成了一种新型的人字形阳离子脂质 (2ss HLL),它由亲水性天冬氨酸和两条还原敏感可断裂的疏水油酸尾链组成.通过siRNA和基于2ss HLL的脂质体间的静电相互作用,成功制备了粒径约150 nm的均匀的球形阳离子纳米复合物.从评估结果可以看出,该纳米复合物在Hep G2细胞试验中表现出较好的细胞摄取和较低的细胞毒性.RT-PCR分析结果表明,2ss HLL/si EGFR纳米复合物可表现出与Lipofectamine2000相类似的对靶mRNA显著的下调效应.这些增强的siRNA基因沉默效率可能归因于还原响应性断裂所诱导的疏水尾链的分离.在还原环境中观察到的纳米复合物的粒径和siRNA释放的变化也证实了上述的机制.由此,我们认为氧化还原响应型2ss HLL将有可能成为siRNA递送的潜在纳米载体.“,”To achieve a higher transfection efficiency and lower toxicity, a novel herringbone-like cationic lipid (2 ss HLL) composed of hydrophilic aspartic acid linked with two reduction-responsive cleavable hydrophobic oleic acid tails was synthesized and assessed in this study. In our results, the cationic nanoplexes with a uniform spherical shape and a particle size of ～150 nm were successfully prepared by the electrostatic interaction between si RNAs and 2 ss HLL-based liposomes. From the results evaluated in Hep G2 cells, it was shown that the nanoplexes exhibited high cellular uptake of si RNA with a low cytotoxicity. Moreover, the significant down-regulation effects of 2 ss HLL/si EGFR nanoplexes on target m RNA were displayed by RT-PCR analysis, which were similar to those of Lipofectamine2000. It suggested that the enhanced si RNA gene silencing efficiency was probably attributed to the detachment of hydrophobic tail chains induced by reduction-responsive cleavage. This mechanism was also confirmed by the changes of size distribution and si RNA release of nanoplexes in the reductive environment and DTT-absence condition. Overall, we believed that the redox-active herringbone-like 2 ss HLL would be a potential nanocarrier towards si RNA delivery.