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Abstract
Advanced chemotherapy strategies are in urgent demand for improving anticancer efficacy. Herein, a water-soluble pillar[6]arene (WP6A) was used to load chemotherapeutic agent pemetrexed (PMX) by forming direct host-guest inclusion, which is beneficial for decreasing cytotoxicity of PMX on BEAS-2B cells. NMR and florescence titration served to confirm the complexation between WP6A and ATP with higher affinity [(5.67 ± 0.31) × 105 L/mol], favoring competitive replacement of PMX. Complexation ATP by WP6A effectively prevented ATP from being hydrolyzed in presence of alkaline phosphatase. The formed host-guest complex was further used to block the efflux pump by cutting off energy source from ATP hydrolysis, which was accompanied with releasing PMX to produce synergistic enhancement of anticancer performance towards A549 cells. This supramolecular strategy would also be extended to other clinical chemotherapeutic agents and it was expected to provide salutary profits for cancer patients.
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