A hybrid semiconducting organosilica-based O₂ nanoeconomizer for on-demand synergistic photothermally boosted radiotherapy

The outcome of radiotherapy is significantly restricted by tumor hypoxia. To overcome this obstacle, one prevalent solution is to increase intratumoral oxygen supply. However, its effectiveness is often limited by the high metabolic demand for O₂ by cancer cells. Herein, we develop a hybrid semiconducting organosilica-based O₂ nanoeconomizer pHPFON-NO/O₂ to combat tumor hypoxia. Our solution is twofold: first, the pHPFON-NO/O₂ interacts with the acidic tumor microenvironment to release NO for endogenous O₂ conservation; second, it releases O₂ in response to mild photothermal effect to enable exogenous O₂ infusion. Additionally, the photothermal effect can be increased to eradicate tumor residues with radioresistant properties due to other factors. This “reducing expenditure of O₂ and broadening sources” strategy significantly alleviates tumor hypoxia in multiple ways, greatly enhances the efficacy of radiotherapy both in vitro and in vivo, and demonstrates the synergy between on-demand temperature-controlled photothermal and oxygen-elevated radiotherapy for complete tumor response.