Key Laboratory of Mesoscopic Chemistry of MOE, Center for Multimolecular Chemistry, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210093, China.
J Am Chem Soc. 2013 Jul 17;135(28):10542-9. doi: 10.1021/ja405014r. Epub 2013 Jul 9.
The drug delivery system based on supramolecular vesicles that were self-assembled by a novel host-guest inclusion complex between a water-soluble pillar[6]arene (WP6) and hydrophobic ferrocene derivative in water has been developed. The inclusion complexation between WP6 and ferrocene derivative in water was studied by (1)H NMR, UV-vis, and fluorescence spectroscopy, which showed a high binding constant of (1.27 ± 0.42) × 10(5) M(-1) with 1:1 binding stoichiometry. This resulting inclusion complex could self-assemble into supramolecular vesicles that displayed a significant pH-responsive behavior in aqueous solution, which were investigated by fluorescent probe technique, dynamic laser scattering, and transmission electron microscopy. Furthermore, the drug loading and in vitro drug release studies demonstrated that these supramolecular vesicles were able to encapsulate mitoxantrone (MTZ) to achieve MTZ-loaded vesicles, which particularly showed rapid MTZ release at low-pH environment. More importantly, the cellular uptake of these pH-responsive MTZ-loaded vesicles by cancer cells was observed by living cell imaging techniques, and their cytotoxicity assay indicated that unloaded vesicles had low toxicity to normal cells, which could dramatically reduce the toxicity of MTZ upon loading of MTZ. Meanwhile, MTZ-loaded vesicles exhibited comparable anticancer activity in vitro as free MTZ to cancer cells under examined conditions. This study suggests that such supramolecular vesicles have great potential as controlled drug delivery systems.
基于超分子囊泡的药物传递系统，该超分子囊泡由在水中通过新型主体-客体包合复合物自组装而成，主体是水溶性的柱[6]芳烃（WP6），客体是疏水性二茂铁衍生物。通过（1）H NMR、UV-vis 和荧光光谱研究了 WP6 和二茂铁衍生物在水中的包合作用，结果表明其结合常数为（1.27 ± 0.42）×10(5) M(-1)，具有 1:1 的结合计量比。所得的包合物可以自组装成超分子囊泡，在水溶液中显示出显著的 pH 响应行为，这通过荧光探针技术、动态激光散射和透射电子显微镜进行了研究。此外，药物负载和体外药物释放研究表明，这些超分子囊泡能够包载米托蒽醌（MTZ），从而实现 MTZ 负载囊泡，在低 pH 环境下表现出快速的 MTZ 释放。更重要的是，通过活细胞成像技术观察到这些 pH 响应的 MTZ 负载囊泡被癌细胞摄取，其细胞毒性测定表明，未负载的囊泡对正常细胞的毒性较低，当负载 MTZ 时，可显著降低 MTZ 的毒性。同时，在研究条件下，负载 MTZ 的囊泡在体外对癌细胞的抗癌活性与游离 MTZ 相当。这项研究表明，这种超分子囊泡具有作为控制药物传递系统的巨大潜力。
