Creating Single Atomic Coordination for Hypoxia-Resistant Pyroptosis Nano-Inducer to Boost Anti-Tumor Immunotherapy

General synthesis and mechanical understanding of type I nano-photosensitizers are of great importance for hypoxia-resistant pyroptosis inducers. Herein, a simple solvothermal treatment is developed to convert non-photosensitive small molecules (hemin) into uniform carbon nanodots (HNCDs) with strong type I photodynamic activity and red fluorescence emission. These HNCDs inherit the single atomic Fe-N₄ center of hemin while creating sp²-hybridized carbon surroundings, which synergistically modulated the energy level and electron transfer for converting the type II photodynamic process to type I. After encapsulating HNCDs with bovine serum albumin (BSA) to facilitate in vivo applications, the resulting BSA nanoparticles (HB) can image tumors and significantly induce the pyroptosis of tumor cells even under an extremely hypoxic environment (2% O₂). This evokes a strong antitumor immune response, effectively restraining tumor growth and lung metastasis in triple-negative breast cancer mice, with good biocompatibility. This work introduces an applicable pyroptosis nano-inducer to combat hypoxic tumors and highlights the regulation of Fe-N₄ centers to develop hypoxia-resistant type I nano-photosensitizers for cancer treatment.