Journal of Chinese Pharmaceutical Sciences ›› 2018, Vol. 27 ›› Issue (6): 383-396.DOI: 10.5246/jcps.2018.06.039

• Original articles • Previous Articles     Next Articles

Novel cationic lipid with reduction-responsive cleavable hydrophobic tail for siRNA delivery

Yi Yan1, Shihe Cui1, Jing Sun1, Piaopiao Li1, Haitao Zhang1,2, Jiancheng Wang1*   

  1. 1. Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China 
    2. School of Pharmaceutical Sciences, Central South University, Changsha 410013, Hunan, China

  • Received:2018-05-06 Revised:2018-05-28 Online:2018-06-30 Published:2018-06-03
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  • Supported by:

    National Natural Science Foundation of China (Grant No. 81473158, 81690264 and 81773650), the New Drug R&D program of China (Grant No. 2018ZX09721003-004) and the Opening Project of Key Laboratory of Drug Targeting and Drug Delivery System, Ministry of Education (Sichuan University).


To achieve a higher transfection efficiency and lower toxicity, a novel herringbone-like cationic lipid (2ssHLL) 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 siRNAs and 2ssHLL-based liposomes. From the results evaluated in HepG2 cells, it was shown that the nanoplexes exhibited high cellular uptake of siRNA with a low cytotoxicity. Moreover, the significant down-regulation effects of 2ssHLL/siEGFR nanoplexes on target mRNA were displayed by RT-PCR analysis, which were similar to those of Lipofectamine2000. It suggested that the enhanced siRNA 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 siRNA release of nanoplexes in the reductive environment and DTT-absence condition. Overall, we believed that the redox-active herringbone-like 2ssHLL would be a potential nanocarrier towards siRNA delivery.

Key words: siRNA delivery, Disulfide bond, Reduction-responsive, Nanoplexes, Cleavage

CLC Number: