Ferric iron coordinated cisplatin prodrug reprograms the immune-cold tumor microenvironment through tumor hypoxia relief for enhanced cancer photodynamic-immunotherapy

The microenvironment of hypoxia and immune-cold limits the therapeutic outcomes of immune checkpoint blockade (ICB) therapy in solid tumors. It is important and imperative to search new strategies to relieve tumor hypoxia and reverse immunosuppression of cold tumors. In this study, the oxygen (O₂) self-replenishing nano-enabled coordination platform can be used to induce potent antitumor immune response in cold tumors. The nanoplatform can produce O₂ by catalyzing hydrogen peroxide (H₂O₂) in tumor site effectively, showing excellent photodynamic therapy (PDT) performance. Meanwhile, it can further trigger immunogenic cell death (ICD), enhance T cell infiltration, reverse immunosuppression, and reprogram the immune-cold tumor microenvironment. In vitro and in vivo results demonstrate that the nanoplatform has potential for eradicating tumors and long-term immunological memory effect. The nanoplatform opens up a strategy for reprograming the immunosuppressive microenvironment in cold tumors.