Huang Zheng, Zhao Dong-Mei, Deng Xuan, Zhang Ji, Zhang Yi-Mei, Yu Xiao-Qi
Key Laboratory of Green Chemistry & Technology (Ministry of Education), College of Chemistry, Sichuan University, Chengdu 610064, China.
Nanomaterials (Basel). 2018 Feb 17;8(2):115. doi: 10.3390/nano8020115.
The studies of bolaamphiphile-based nanoparticles as delivery vectors are still rudimentary and under development. In this study, several asymmetric bolaamphiphiles containing lysine and another moiety with special functions, such as pH-sensitive or cell-targeting property, were designed and synthesized. The potentials of these bolaamphiphile-based nanoparticles as versatile vectors for both nucleic acids and chemical drugs were studied. With the presence of 1,2-dioleoyl--glycero-3-phosphoethanolamine (DOPE), these amphiphiles could be prepared into bolasomes, which showed good DNA binding ability and could condense plasmid DNA into nanoparticles with appropriate size and surface potential. , which has a pH-sensitive histidine on one head, exhibited higher transfection efficiency than the symmetric counterpart and comparable efficiency to commercially available transfection reagent. Mechanism studies confirmed that the bolaplexes formed from might induce the highest cellular uptake and the best endosomal escape ability. On the other hand, these bolaamphiphiles also exhibited good drug loading ability. The self-assembly vesicles could efficiently encapsulate the hydrophobic anti-cancer drug doxorubicin (DOX) in aqueous solution with high drug loading content and encapsulation efficiency. Confocal laser scanning microscopy (CLSM) experiment and cell viability assay exhibited a controlled release of the drug with the assistance of bolasomes. It was shown that such bolaamphiphiles have great potential as nano-vectors for both drug and gene or their co-delivery.
基于双性离子两亲分子的纳米颗粒作为递送载体的研究仍处于初级阶段且正在发展中。在本研究中，设计并合成了几种含有赖氨酸和另一种具有特殊功能（如pH敏感性或细胞靶向性）部分的不对称双性离子两亲分子。研究了这些基于双性离子两亲分子的纳米颗粒作为核酸和化学药物通用载体的潜力。在1,2 - 二油酰基 - sn -甘油 - 3 - 磷酸乙醇胺（DOPE）存在的情况下，这些两亲分子可制备成双性离子脂质体，其显示出良好的DNA结合能力，并能将质粒DNA浓缩成具有合适尺寸和表面电位的纳米颗粒。其中一种在一个头部具有pH敏感的组氨酸，其转染效率高于对称对应物，且与市售转染试剂效率相当。机制研究证实，由其形成的双性离子脂质体复合物可能诱导最高的细胞摄取和最佳的内体逃逸能力。另一方面，这些双性离子两亲分子也表现出良好的载药能力。自组装囊泡能够在水溶液中高效包封疏水性抗癌药物阿霉素（DOX），具有高载药量和包封效率。共聚焦激光扫描显微镜（CLSM）实验和细胞活力测定表明，在双性离子脂质体的辅助下药物实现了控释。结果表明，此类双性离子两亲分子作为药物和基因的纳米载体或其共递送载体具有巨大潜力。
