两亲性柱[5]芳烃超分子纳米载药体系的构筑及其抗肿瘤活性研究

Construction and Antitumor Activity of Supramolecular Nano Drug Delivery System Based on Amphiphilic Pillar[5]arene

合成了一种新型的丙氨酸取代水溶性柱[5]芳烃DAP5,以此作为构建单元可与十二烷基苯磺酸钠(SDBS)通过主客体作用构筑出可高效包载抗癌药物阿霉素(DOX)的超分子纳米载体SDBS∈DAP5,包封率为62.6%。该纳米载药体系不仅具有较好的pH响应性能并在模拟肿瘤弱酸性微环境中可持续释放药物,而且对正常肝细胞(LO2)具有较低的毒性(半抑制浓度IC_(50)>10μmol/L),重要的是对四种测试的癌细胞(Hela、HepG2、MGC-803和T24)表现出比裸药更强的增殖抑制活性和更短的用药时间。其中,对于HepG2效果更为显著,作用24h后,其IC_(50)为0.77μmol/L,约为裸药DOX(3.43μmol/L)的22%。上述结果为超分子载药体系在未来肿瘤的治疗中提高药物的有效性以及降低毒副作用提供了重要的参考信息。

A novel alanine substituted water-soluble pillar[5]arene DAP5 was synthesized,which could be used as building block to construct a supramolecular nano drug loading carrier SDBS?DAP5 through host-guest interaction with sodium dodecylbenzene sulfonate(SDBS).This carrier can efficiently encapsulate DOX with an entrapment efficiency of 62.6%.And its nano drug delivery system DOX∈SDBS∈DAP5 not only had good pH response performance and could continuously release the drug in a simulated weak acid tumor microenvironment,but also had low toxicity to normal liver cells(LO2)(IC_(50)>10μmol/L).More importantly,DOX∈SDBS∈DAP5 exhibited stronger proliferation inhibition activity and shorter medication time over free drug for four tested cancer cells(Hela,HepG2,MGC-803 and T24).Especially for HepG2,after 24 hours of incubation with drug,IC_(50) of DOX?SDBS?DAP5 was 0.77μmol/L,about 22%of that of DOX(3.43μmol/L).These results provide important reference information for improving the efficacy and reducing the side effects of supramolecular drug delivery system in the future cancer treatment.