Designing an Osmium(II) Complex to Inhibit the Growth and Recurrence of Tumors by Integrating Photodynamic Therapy, Chemotherapy, and Immunotherapy

To effectively inhibit the growth and recurrence of tumors, we proposed to design a new osmium (Os) complex integrating photodynamic therapy (PDT), chemotherapy, and immunotherapy. To this end, we optimized a series of Os(II) complexes derived from differently modified thiosemicarbazone ligands to obtain an Os(II) 2-quinoxalinecarbaldehyde thiosemicarbazone complex (Os3) with remarkable cytotoxicity and phototoxicity to cancer cells. The establishment of an MC38 colon cancer xenograft model demonstrated that Os3 not only significantly inhibited the growth and recurrence of tumors but also exhibited few side effects. We confirmed that the antitumor ability of Os3 was attributed to the generation of phototoxicity, action on DNA, mitochondrial damage, induction of BRD4-mediated apoptosis, induction of ferroptosis, and activation of ferroptosis-mediated immune response.