Mitochondria-localized photocatalyst of biomimetic organic semiconductor nanoparticles for NIR-activatable photocatalytic immunotherapy

Photocatalytic therapy holds great prospects in high-performance tumor treatment owing to its advantages of noninvasiveness and oxygen nonreliance. However, there is still a lack of ideal photocatalyst materials that respond to near-infrared (NIR) light, especially with organelle-specific features. Here, a mitochondria-biomimetic organic semiconductor photocatalyst was designed for NIR-activatable photocatalytic immunotherapy of recurrent and metastatic tumor. With biomimetic of mitochondrial membrane, a NIR-responsive conjugated polymer YBSe-SS was prepared into biomimetic nano-photocatalysts (Mito-NPs). Upon NIR-light irradiation, the Mito-NPs achieved effective photocatalytic oxidation of reduced nicotinamide adenine dinucleotide and mitochondria dysfunction, benefiting from the mitochondria-targeted performance. Also, relatively high multiphototheranostics were demonstrated by the Mito-NPs. Subsequently, with Mito-NP-regulated mitochondrial function and metabolism, the in vivo experiments proved that the photocatalytic Mito-NPs combined with immune checkpoint therapy achieved photocatalytic immunotherapy for suppressing primary and pulmonary metastasis of osteosarcoma. This work offers a practical paradigm for NIR-activatable organic photocatalytic materials for high-performance tumor therapy.