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Traditional combination therapy of photodynamic therapy (PDT) and photothermal therapy (PTT) is limited in the field of clinical cancer therapy due to activation by light with separate wavelengths, insufficient O 2 supply, antioxidant ability of glutathione (GSH) in tumor cell, and low penetration depth of light. Here, a multifunctional nanoplatform composed of MoO 3-x nanosheets, Ag nanocubes, and MnO 2 nanoparticles was developed to overcome these drawbacks. For this nanoplatform, hyperthermia and reactive oxygen species (ROS) were simultaneously generated under single 808 nm near-infrared (NIR) light irradiation. Once this nanoplatform accumulated in the tumor region, GSH was depleted by MnO 2 and intracellular H 2 O 2 was catalyzed by MnO 2 to produce O 2 to relieve hypoxia. Ultrasound (US) imaging confirmed in-situ O 2 generation. Magnetic resonance (MR) imaging, photoacoustic (PA) imaging, and fluorescence imaging were used to monitor in vivo biodistribution of nanomaterials. This provides a paradigm to rationally design a single NIR laser induced multimodal imaging-guided efficient PDT/PTT cancer strategy. [Display omitted] • Hyperthermia and ROS were simultaneously generated under single 808 nm NIR light irradiation. • The depletion of GSH and the decomposition of endogenous H 2 O 2 for generating oxygen against hypoxic. • Multimodal imaging can visualize the tumor site for pretreatment guidance and real-time monitoring in the PTT/PDT treatment. [ABSTRACT FROM AUTHOR]

• The FeOCl@PB@PDA@BPQDs@Mn nanocomposites could catalyze H 2 O 2 to generate O 2 and successfully ameliorated tumor hypoxia. • The FeOCl@PB@PDA@BPQDs@Mn nanocomposites showed excellent photothermal performance and ROS generation. • The FeOCl@PB@PDA@BPQDs@Mn nanocomposites can serve as a multimodal imaging agent for MR, PA, and US imaging. • The FeOCl@PB@PDA@BPQDs@Mn nanocomposites can act as an ideal theranostic agent for combined CDT, PDT, and PTT. Herein, a novel tumor microenvironment (TME)-mediated nanotheranostics platform of iron oxychloride (FeOCl) nanorods coated with Prussian Blue (PB), polydopamine (PDA), black phosphorus quantum dots (BPQDs) and chelated with Mn2+ was prepared. In the highly integrated nanoplatform (FeOCl@PB@PDA@BPQDs@Mn), FeOCl catalysts exhibit supreme efficiency to yield hydroxyl radicals (•OH) by H 2 O 2 decomposition for chemodynamic therapy (CDT). Moreover, the PB, FeOCl, and Mn2+ have a catalase-like activity that catalyze H 2 O 2 to release of O 2 in the TME. Upon laser irradiation, the BPQDs transform O 2 to a singlet oxygen (1O 2) to self-enhance photodynamic therapy (PDT). Additionally, as a result of the high near-infrared (NIR) absorption rate and efficient photothermal conversion of PB and PDA, FeOCl@PB@PDA@BPQDs@Mn nanocomposites (NCs) are capable to work as ideal theranostic agents for photothermal therapy (PTT) in vitro and in vivo. Furthermore, FeOCl@PB@PDA@BPQDs@Mn NCs can also serve as multimodal imaging agents in different methods, such as magnetic resonance (MR), photoacoustic (PA), and ultrasound (US) imaging. Among the tumor models of mice, CDT, PDT, and PTT that combined with multimodal imaging achieved a more significant synergistic therapeutic result compared to any single treatment modality alone. Therefore, the multifunctional nanosystem in this study possesses tremendous potential in providing a satisfying paradigm for effective tumor treatment. [ABSTRACT FROM AUTHOR]