A Deep-Red-Absorbing Osmium(II) Complex as a Photosensitizer for Photodynamic Therapy Inducing Immunogenic Cell Death

Area of Science:

• Materials Science
• Chemical Biology
• Immunology

Background:

• Immunogenic cell death (ICD) is crucial for developing novel anticancer therapies by converting tumor cells into vaccines.
• Osmium(II) polypyridyl complexes are being explored for their therapeutic potential in cancer treatment.

Purpose of the Study:

• To synthesize and evaluate osmium(II) polypyridyl complexes as photosensitizers for cancer therapy.
• To investigate the mechanism of action, including photodynamic therapy (PDT) and immunogenic cell death (ICD) induction.
• To assess the in vitro and in vivo efficacy of the most promising compound.

Main Methods:

• Synthesis of a series of osmium(II) polypyridyl complexes.
• Evaluation of dark toxicity and phototoxicity against various cancer cell lines.
• Mechanism studies involving reactive oxygen species (ROS) generation (Type-I and Type-II pathways).
• In vitro and in vivo assessment of ICD induction and anti-tumor effects using CT26 and MCA205 cell lines.
• Comprehensive immune analysis in mice, including T cell activation and macrophage reprogramming.

Main Results:

• The compound Os2 demonstrated significant phototoxicity via photogeneration of ¹O₂ and •OH, acting through Type-I and Type-II mechanisms.
• Os2 effectively induced immunogenic cell death (ICD) in CT26 and MCA205 cells upon 740 nm irradiation, both in vitro and in vivo.
• Mice treated with Os2-modified CT26-luc cells showed enhanced systemic adaptive immune responses, including CD8+ T cell activation and macrophage reprogramming.
• Significant inhibition of tumor growth was observed in vivo.

Conclusions:

• Os2 is identified as a highly effective photosensitizer for photodynamic therapy and a potent inducer of immunogenic cell death.
• Os2 represents the first photoactive osmium-based complex capable of inducing ICD, offering a novel platform for cancer immunotherapy.
• The study highlights the potential of Os2 in developing new cancer vaccines and therapies by harnessing the immune system against tumors.