Supramolecular Chemotherapy: Carboxylated Pillar[6]arene for Decreasing Cytotoxicity of Oxaliplatin to Normal Cells and Improving Its Anticancer Bioactivity Against Colorectal Cancer.

We have successfully demonstrated that the host-guest complex of carboxylated pillar[6]arene with oxaliplatin (OxPt) exhibits low cytotoxicity toward normal cells and displays higher anticancer bioactivity against colorectal cancer cells than OxPt itself. Owing to higher binding affinity of carboxylated pillar[6]arene with spermine (SPM) than that with OxPt, the encapsulated OxPt can be thoroughly released from its host-guest complex by the competitive replacement with SPM. This supramolecular chemotherapy works well both in vitro and in vivo for SPM-overexpressed cancers, such as colorectal cancer. Compared to OxPt itself, the anticancer bioactivity of this host-guest complex is further improved by about 20%. Such an improvement results from the combined effect of controlled release of OxPt from its host-guest complex and simultaneous consumption of SPM by carboxylated pillar[6]arene. It is anticipated that this supramolecular strategy may be extended to other clinical anticancer drugs for decreasing their severe side effects and improving their anticancer bioactivity, thus enriching the realm of supramolecular chemotherapy.