A Cleavable Self-Inclusion Conjugate with Enhanced Biocompatibility and Antitumor Bioactivity

The effective encapsulation of antitumor drugs by dynamic host–guest interactions at the submicromolar level remains a challenge.Herein,we report a cleavable self-inclusion camptothecin-cucurbit[7]uril(CPT-CB[7])conjugate.The binding affinity of CB[7]to CPT is greatly enhanced owing to the intramolecular self-inclusion,demonstrating a concentrationindependent encapsulation efficiency of nearly 100%.The disulfide linker of CPT-CB[7]conjugate can be cleaved in the reductive tumor microenvironment,transforming the self-inclusion into a binary host–guest complexation pattern,thus releasing the CPT thoroughly.The enhanced biocompatibility and antitumor bioactivity of the cleavable self-inclusion conjugate have been confirmed by in vitro and in vivo experiments.This line of research will open new horizons for supramolecular drug delivery systems operating in diluted and competitive conditions.