Multifunctional MnO 2 /Ag 3 SbS 3 Nanotheranostic Agent for Single-Laser-Triggered Tumor Synergistic Therapy in the NIR-II Biowindow.

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 (H 2 O 2 ) 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 MnO 2 /Ag 3 SbS 3 (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, MnO 2 /Ag 3 SbS 3 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, MnO 2 /Ag 3 SbS 3 NPs will be degraded to Mn 2+ and Ag 3 SbS 3 . The released Ag 3 SbS 3 NPs as a NIR-II phototherapy agent could be utilized for photoacoustic imaging-guided NIR-II PDT/PTT. Mn 2+ could be used as a Fenton-like catalyst to continuously catalyze endogenous H 2 O 2 for generating highly virulent hydroxyl radicals ( • OH) for CDT and O 2 for PDT, enhancing the efficiency of PDT and CDT, respectively. Meanwhile, Mn 2+ realizes magnetic resonance imaging-guided accurate tumor therapy. Moreover, the MnO 2 /Ag 3 SbS 3 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 H 2 O 2 for efficient and precise cancer treatment.