arene / ATP host – guest recognition : selectivity , inhibition of ATP hydrolysis , and application in multidrug resistance treatment †

Due to the differences in the cavity size of the hosts and the charge and length of the guests, a cationic water-soluble pillar[6]arene (WP6) selectively complexes with ATP to form a stable 1 : 1 inclusion complex WP6IATP. This host–guest complexation was utilized to efficiently inhibit the hydrolysis of ATP, arising from the existence of the hydrophobic cavity of WP6. A folic acid functionalized diblock copolymer (FA-PEG-b-PAA) was employed to PEGylate WP6 to endow the polyion complex (PIC) micelles with specific targeting ability, preferentially delivering WP6 to folate receptor over-expressing KB cell. This host–guest complexation was further used to block the efflux pump to transport anticancer drugs out of cells by cutting off the energy source, which enhanced the efficacy of the cancer chemotherapy of DOX$HCl towards drug resistant MCF-7/ADR cell. This supramolecular method provides an extremely distinct strategy to potentially overcome multidrug resistance (MDR).

由于主体的空腔大小以及客体的电荷和长度存在差异，一种阳离子水溶性柱[6]芳烃（WP6）选择性地与三磷酸腺苷（ATP）络合，形成稳定的1∶1包合物WP6⊃ATP。这种主 - 客体络合作用被用于有效抑制ATP的水解，这是由于WP6存在疏水空腔。一种叶酸功能化的两嵌段共聚物（FA - PEG - b - PAA）被用于将WP6聚乙二醇化，使聚离子复合物（PIC）胶束具有特定的靶向能力，优先将WP6递送至叶酸受体过度表达的KB细胞。这种主 - 客体络合作用还被进一步用于阻断外排泵通过切断能量来源将抗癌药物运出细胞，这提高了盐酸阿霉素（DOX·HCl）对耐药MCF - 7/ADR细胞的癌症化疗效果。这种超分子方法为潜在克服多药耐药性（MDR）提供了一种截然不同的策略。