A supramolecular organometallic drug complex with H2O2 self-provision intensifying intracellular autocatalysis for chemodynamic therapy

Abstract

Chemodynamic therapy (CDT) can efficiently combat tumor cells through a robust catalyst in the presence of H₂O₂. However, the insufficient intracellular H₂O₂ level and inefficiency of catalysts in tumor cells limit the production of enough toxic hydroxyl radicals (˙OH) to achieve satisfactory efficacy for CDT. Herein, a supramolecular organometallic drug complex (SOMDC) with H₂O₂ self-provision was proposed to intensify the intracellular autocatalysis for enhancing the CDT effect. The obtained SOMDC could self-assemble into supramolecular organometallic drug micelles (SOMDMs), which could be effectively dissociated because the endogenous H₂O₂ in tumor cells can rapidly destroy the host–guest interactions. The released DOX prodrug effectively upregulated the endogenous H₂O₂ level and amplified the Fenton-like intracellular autocatalysis to guarantee a remarkable ˙OH production for improving CDT efficiency. In vitro and in vivo evaluations showed that SOMDC exhibited excellent anticancer activity with reduced toxicity to normal tissues. Therefore, this novel strategy with H₂O₂ self-provision to intensify intracellular autocatalysis for enhancing the CDT effect may provide new insights for cancer therapy.