Chemotherapy is among the most important modalities for clinical anticancer treatment. However, common chemotherapeutic drugs still have several disadvantages including high cytotoxicity to normal cells and low specificity to cancer cells. To address these issues, we have collaborated with Prof. Zhiwei Sun and Dr. Yueyue Chen from Capital Medical University and presented a new strategy of “supramolecular chemotherapy”.

　Supramolecular chemotherapy aims to employ supramolecular chemistry to reduce cytotoxicity of chemotherapeutic drugs to normal cells and improve their anticancer bioactivity. In cancer microenvironments, some cancer biomarkers are overexpressed (e.g. spermine bearing many positive charges) as essential components for cell growth and proliferation. Upon this point, we decided to utilize macrocyclic hosts to encapsulate anticancer drugs for decreasing their cytotoxicity to normal cells and using cancer biomarkers to selectively release them in cancer microenvironments. On the one hand, cancer biomarkers can competitively bind with macrocyclic hosts and replace anticancer drugs, thus recovering their anticancer bioactivity. On the other hand, cancer biomarkers can be consumed by macrocyclic hosts as well. Thus, these two simultaneous events could result in further improvement of anticancer bioactivity.

　We have utilized cucurbit[7]uril (CB[7]) to encapsulate a model anticancer drug of dimethyl viologen and a clinical anticancer drug of oxaliplatin for successfully demonstrating supramolecular chemotherapy. Taking oxaliplatin as an example, the host-guest complex of oxaliplatin and CB[7] exhibited decreased cytotoxicity to normal cells. Owing to overexperssed spermine in the microenvironments of lung and colorectal cells, oxaliplatin could be released by competitive replacement and kill cancer cells; in the meantime, the host-guest complexation between spermine and CB[7] could reduce the concentration of spermine in cancer microenvironments, thus promoting their cell apoptosis. Therefore, the host-guest complex of oxaliplatin and CB[7] displayed higher anticancer bioactivity than oxaliplatin itself. It is anticipated that this strategy of supramolecular chemotherapy with concise design has considerable potentials for practical applications in spermine-overexpressed cancer treatments.