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Tumor oxygen spatial heterogeneity is a critical challenge for the photodynamic inhibition of solid tumors. Development of an intelligent nanoagent to initiate optimal therapeutics according to the localized oxygen levels is an effective settlement. Herein, we report an activatable nanoagent (BDP-Oxide nanoparticles (NPs)) to enable the oxygen auto-adaptive photodynamic/photothermal complementary treatment. Upon the nanoagent accumulated in the tumor region, the low extracellular pH could trigger the disassociation of the nanoagent to release the phototheranostic agent, BDP-Oxide, which will subsequently afford the fluorescence imaging-guided photodynamic oxidation after it gets into the outer oxygen-rich tumors. Along with the penetration deepening in the solid tumor, furthermore, BDP-Oxide could be reduced into BDP by the cytochrome P450 (CYP450) enzymes activated in the low oxygen tension regions of inner hypoxic tumors, which will switch on the photothermal and photoacoustic effects. Overall, the BDP-Oxide NPs-enabled photodynamic/photothermal complementary therapy significantly suppressed the solid tumor growth (inhibition rate of 94.8%). This work proposes an intelligent platform to address the oxygen partial pressure for the optimization of cancer phototherapeutics.
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