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.

肿瘤氧空间异质性是实体瘤光动力抑制的关键挑战。开发智能纳米试剂以根据局部氧水平启动最佳治疗是一种有效的解决方案。在此，我们报告了一种可激活的纳米剂（BDP-氧化物纳米颗粒（NPs）），以实现氧自适应光动力/光热互补处理。当纳米试剂在肿瘤区域积累时，细胞外的低 pH 值会触发纳米试剂的解离，释放出光热治疗剂 BDP-Oxide，随后在进入富含氧气的外部后提供荧光成像引导的光动力氧化。肿瘤。随着在实体瘤中渗透的加深，此外，BDP-Oxide 可被细胞色素 P450 (CYP450) 酶在内部缺氧肿瘤的低氧张力区激活，还原为 BDP，从而开启光热和光声效应。总体而言，BDP-Oxide NPs 启用的光动力/光热互补疗法显着抑制了实体瘤的生长（抑制率为 94.8%）。这项工作提出了一个智能平台来解决氧分压，以优化癌症光疗法。