Facile synthesis of intelligent semi-salamo Cu (II) complex with glutathione depletion for enhanced chemodynamic therapy

Due to its high selectivity, chemokinetic therapy (CDT), which uses Fenton catalyst to kill cancer cells by converting intracellular H2O2 into highly toxic hydroxyl radicals (.OH), has shown potential application in the treatment of tumors. Nevertheless, the presence of overexpressed glutathione (GSH) in tumor cells limits the lethal effect of this treatment on tumors. Herein, an intelligent semi-salamo-type copper complex (CuL1) was synthesized to consume excess glutathione (GSH) in tumor cells for enhanced CDT. Research on the crystal structure of CuL1 indicates that the formed complex self-assembles through intermolecular hydrogen bonding interactions, resulting in a three-dimensional supramolecular shape that can be infinitely stretched inward. After being internalized by tumor cells, CuL1 can be degraded and reduced by GSH, resulting in the generation of high concentrations of Cu (I). The subsequent Fenton-like reaction resulted in excessive Cu (I) ions binding with H2O2 to produce highly toxic .OH, increasing the efficacy of CDT. Our findings can be utilized to create more intelligent metal-based anticancer drugs and improve the effectiveness of tumor CDT.