Overcoming oxygen heterogeneity of tumor microenvironments to boost cancer immunotherapy by oxygen-switchable ROS/RNS nanogenerators

The spatiotemporal heterogeneity of oxygen not only represents a hallmark of malignant tumors but also determines the degree and persistence of immunotherapy response in solid tumors. Smart materials that can adapt to pathological oxygen levels and generate immunogenic stimuli to improve immunotherapy are highly desirable. Here, we develop oxygen-switchable reactive oxygen species/nitrogen species nanogenerators (RO/NS NGs) to overcome the oxygen heterogeneity of tumors and boost cancer immunotherapy. Upon receiving laser irradiation, the tetraphenylporphyrin moieties within RO/NS NGs serve as photosensitizers to generate ROS under normoxia and photocatalysts to activate nitric oxide donors to release RNS under hypoxia. Both ROS and RNS can induce immunogenic cell death in both normoxic and hypoxic tumor cells, stimulate dendritic cell maturation, and increase the infiltration of cytotoxic T cells into tumors. This work provides a feasible means for overcoming oxygen heterogeneity to boost immunotherapy.