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.