NIR‐II Photoactivatable Cobalt(III) Nanoparticles for Photoactivated Metal Chemo‐Immunotherapy

Abstract Photoactivated cobalt(III) (Co(III)) complexes have great potential for cancer therapy due to their unique interactions with cancer cells. However, its clinical application remains limited by its high toxicity due to low spatial‐temporal control. Here, a second near‐infrared window (NIR‐II) photoactivated Co(III) nanoparticles (NanoCo) is shown. Under 1064 nm light irradiation, NanoCo is capable of generating photothermal heat to accelerate the reduction of Co(III) to Co(II). Under hypoxic conditions, NanoCo is 166 times more effective than cisplatin at killing platinum‐resistant A549DDP tumor cells. Notably, when exposed to 1064 nm irradiation, NanoCo becomes 5000 times more effective than oxaliplatin at killing CT26 cells under normoxic conditions. NanoCo accumulates at the tumor site, generating photothermal heat and killing tumor cells under 1064 nm irradiation. Additionally, NanoCo under 1064 nm irradiation triggers immunogenic cell death, further stimulating dendritic cell maturation and inducing anti‐tumor immune responses. The combination of Pt(IV) nanoparticles (HSA@Pt) with NanoCo under 1064 nm irradiation achieves a 99% tumor growth inhibition rate in a 4T1 tumor‐bearing mouse model. This work is the first to introduce Co(III) complexes activated by NIR‐II light for photoactivated chemo‐immunotherapy.