Regulating the level of
reactive oxygen species (ROS) in a
tumor is an efficient and innovative anticancer strategy. However, the therapeutic efficacy of ROS-based
therapies, such as chemodynamic
therapy (CDT) and
photodynamic therapy (
PDT), offers finite outcomes due to the
oxygen dependence and limited concentration of
hydrogen peroxide (H2O2) and overexpression of
glutathione (GSH) within the tumor microenvironment (TME), so a single therapeutic strategy is insufficient to completely eliminate
tumors. Therefore, we demonstrated an omnipotent nanoplatform MnO2/Ag3SbS3 (abbreviated as MA) with strong optical absorbance in the NIR-II biowindow and
oxygen self-sufficient ROS-mediated ability, which not only relieves tumor hypoxia significantly but also enhances the
photothermal therapy (PTT)/
PDT/CDT efficacy. By 1064 nm
laser irradiation, MnO2/Ag3SbS3 nanoparticles (NPs) reveal a favorable photothermal conversion efficiency of 23.15% and achieve a single-
laser-triggered NIR-II PTT/
PDT effect, resulting in effective
tumor elimination. Once internalized into the
tumor, MnO2/Ag3SbS3 NPs will be degraded to Mn2+ and Ag3SbS3. The released Ag3SbS3 NPs as a NIR-II
phototherapy agent could be utilized for photoacoustic imaging-guided NIR-II
PDT/PTT. Mn2+ could be used as a Fenton-like catalyst to continuously catalyze endogenous H2O2 for generating highly virulent
hydroxyl radicals (•OH) for CDT and O2 for
PDT, enhancing the efficiency of
PDT and CDT, respectively. Meanwhile, Mn2+ realizes magnetic resonance imaging-guided accurate
tumor therapy. Moreover, the MnO2/Ag3SbS3 NPs could deplete intracellular GSH in TME to promote oxidative stress of the
tumor, further strengthening ROS-mediated antitumor treatment efficacy. Overall, this work presents a distinctive paradigm of TME-responsive
PDT/CDT/PTT in the second near-infrared biowindow by depleting GSH and decomposing H2O2 for efficient and precise
cancer treatment.