Abstract
Stimuli-responsive supramolecular chemotherapy, particularly in response to cancer biomarkers, has emerged as a promising strategy to overcome the limitations associated with traditional chemotherapy. Spermine (SPM) is known to be overexpressed in certain cancers. In this study, we introduced a novel supramolecular chemotherapy system triggered by SPM. The system featured pyridine salts of a diphenylanthracene derivative (PyEn) and a complementary water-soluble pillar[5]arene (WP5C5) with long alkyl chains. The diphenylanthracene unit of PyEn is effectively encapsulated within the long alkyl chains of WP5C5, resulting in a substantial reduction in the cytotoxicity of PyEn towards normal cells. The therapeutic effect of PyEn is selectively triggered intracellularly through SPM, leading to the endosomal release of PyEn and concurrent in situ cytotoxicity. This supramolecular chemotherapy system exhibits notable tumor inhibition against SPM-overexpressed cancers with reduced side effects on normal tissues. The supramolecular strategy for intracellular activation provides a novel tool with potential applications in chemotherapeutic interventions, offering enhanced selectivity and reduced cytotoxicity to normal cells.
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