Cytotoxicity Regulated by Host–Guest Interactions: A Supramolecular Strategy to Realize Controlled Disguise and Exposure

Abstract

This work is aimed at providing a supramolecular strategy for tuning the cytotoxicity in chemotherapy. To this end, as a proof of concept, we employed dynamic cucurbit[7]­uril­(CB[7])-mediated host–guest interaction to control the loading and releasing of dimethyl viologen (MV) as a model antitumor agent. MV has high cytotoxicity to both normal cells and tumor cells without specificity. By encapsulating MV into the hydrophobic cavity of CB[7], the cytotoxicity of MV to normal cells can be significantly decreased. When the host–guest complex of MV-CB[7] is added into tumor cells with overexpressed spermine, the antitumor activity of MV can be recovered in tumor cell environment. There are two reasons behind this effect: on the one hand, spermine has a high affinity to CB[7], leading to releasing of MV from MV-CB[7]; on the other hand, CB[7] can soak up spermine, which is essential for tumor cell growth, therefore decreasing the cell viability furthermore. Then, it is highly anticipated that this kind of supramolecular strategy could apply to clinical antitumor agents and provide a new approach for decreasing the cytotoxicity and increasing the antitumor activity, thus opening horizons of supramolecular chemotherapy