Ir(III) Complexes Convert Cold to Hot Tumors via Ferroptosis/Necroptosis-Driven Immunogenic Cell Death and Photosensitized CD47 Downregulation - PubMed
2 hours ago
- #photodynamic therapy
- #CD47
- #immunogenic cell death
- Two Ir(III) complexes (Ir1 and Ir2) are developed as photodynamic therapy (PDT) agents that work via Type-I/II mechanisms to overcome hypoxic tumor microenvironments.
- Under 630 nm irradiation, Ir1-mediated PDT downregulates CD47 in a ROS-dependent manner, allowing spatial control and avoiding hematotoxicity, while also blocking the CD47-SIRPα immune checkpoint.
- Ir1-PDT triggers immunogenic cell death (ICD) through a synergy of ferroptosis and necroptosis, and promotes M1-polarization of tumor-associated macrophages.
- In 4T1 murine breast cancer models, Ir1-PDT effectively suppresses tumors and converts immunologically 'cold' tumors into 'hot' ones by combining ICD with disruption of the CD47 pathway.
- This work establishes a photodynamic CD47-signaling platform for precise immune modulation, offering a clinically translatable alternative to existing CD47-targeting therapies.