Rhenium(I) coordinated carbon nitride as type II immunogenic cell death inducers for enhancing photoimmunotherapy against triple-negative breast cancer

Immunotherapy is a promising modality for treating triple-negative breast cancer (TNBC). However, its therapeutic effect is severely restricted by the drug resistance and non-immunogenic tumor microenvironment. Herein, an endoplasmic reticulum (ER)-targeting rhenium(I) coordinated carbon nitride photosensitizer based on Re(CO)5Cl coordinated to g-C3N4 nanosheets can realize photoimmunotherapy against hypoxic-drug resistant TNBC. Compared with the clinical anti-cancer chemotherapy drug doxorubicin, the photosensitizer induces robust ER stress to evoke damage-associated molecular patterns (DAMPs) exposure on the cell surface by a combinatorial interaction mechanism of apoptosis, pyroptosis, ferroptosis, and ICD under two-photon light irradiation. The DAMPs can stimulate the antigen-presenting function of dendritic cells. As a result, a series of immunological responses are activated, including CD8+ and CD4+ T cell proliferation, which effectively inhibited the growth of the primary and secondary distant tumor in vivo. In all, we present a light-dependent type II ICD inducer of metal-based complexes that can conquer drug resistance for hypoxic TNBC, which may have great potential in the substitution of clinical anticancer drugs.