An Activatable Host-Guest Conjugate as a Nanocarrier for Effective Drug Release through Self-Inclusion

There is a challenge in supramolecular chemotherapy for constructing a system equipped with both sufficient protection and high-efficiency release of drugs. To this end, a new strategy of an activatable host-guest conjugate with self-inclusion property is proposed. Based on the binding affinity gain of intramolecular host-guest self-inclusion, an activatable host-guest conjugate was designed, bearing cucurbit[7]uril as the host, an alkyl ammonium moiety as the guest, and the redox-responsive disulfide linkage. Oxaliplatin, a clinical antitumor drug, could be firmly encapsulated by the activatable host-guest conjugate to form the supramolecular drug with high stability. Moreover, oxaliplatin loaded in the activatable host-guest conjugate could be almost completely released by self-inclusion triggered by glutathione in a tumor microenvironment, thus exhibiting comparable antitumor bioactivity with naked oxaliplatin through in vitro cell experiments. It is highly anticipated that this line of research may open new horizons for programmable and on-demand supramolecular chemotherapy with high antitumor efficiency.

Automated summary

A new strategy of activatable host-guest conjugate with self-inclusion property is proposed for supramolecular chemotherapy, which can achieve high-efficiency drug release triggered by intramolecular host-guest self-inclusion. The encapsulation of oxaliplatin in the conjugate leads to the formation of a stable supramolecular drug, and the release of oxaliplatin in the tumor microenvironment shows comparable anti-tumor bioactivity to naked oxaliplatin. This research may open new horizons for programmable and on-demand supramolecular chemotherapy with high anti-tumor efficiency.