Multimode Imaging-Guided Photothermal/Chemodynamic\nSynergistic Therapy Nanoagent with a Tumor Microenvironment Responded\nEffect

Abstract

The\ndevelopment of near-infrared (NIR) laser triggered phototheranostics\nfor multimodal imaging-guided combination therapy is highly desirable.\nHowever, multiple laser sources, as well as inadequate therapeutic\nefficacy, impede the application of phototheranostics. Here, we develop\nan all-in-one theranostic nanoagent PEGylated DCNP@DMSN-MoO<i>_x</i> NPs (DCDMs) with a flower-like structure fabricated\nby coating uniformly sized down-conversion nanoparticles (DCNPs) with\ndendritic mesoporous silica (DMSN) and then loading the ultrasmall\noxygen-deficient molybdenum oxide nanoparticles (MoO<i>_x</i> NPs) inside through an electrostatic interaction. Owing\nto the doping of Nd ions, when excited by an 808 nm laser, DCNPs emit\nbright NIR-II emissions (1060 and 1300 nm), which have characteristic\nhigh spatial resolution and deep tissue penetration. In terms of treatment,\nMoO<i>_x</i> NPs could be specifically activated\nby excessive hydrogen peroxide (H₂O₂) in the\ntumor microenvironment, thus generating ¹O₂ <i>via</i> the Russell mechanism. In addition, the excessive glutathione\n(GSH) in the tumor cells could be depleted through the Mo-mediated\nredox reaction, thus effectively decreasing the antioxidant capacity\nof tumor cells. Importantly, the excellent photothermal properties\n(photothermal conversion efficiency of 51.5% under an 808 nm laser)\nsynergistically accelerate the generation of ¹O₂. This cyclic redox reaction of molybdenum indeed ensured the high\nefficacy of tumor-specific therapy, leaving the normal tissues unharmed.\nMoO<i>_x</i> NPs could also efficiently catalyze\ntumor endogenous H₂O₂ into a considerable amount\nof O₂ in an acidic tumor microenvironment, thus relieving\nhypoxia in tumor tissues. Moreover, the computed tomography (CT) and <i>T</i>₁-weighted magnetic resonance imaging (MRI)\neffect from Gd³⁺ and Y³⁺ ions make DCNPs act\nas a hybrid imaging agent, allowing comprehensive analysis of tumor\nlesions. Both <i>in vitro</i> and <i>in vivo</i> experiments validate that such an “all-in-one” nanoplatform\npossesses desirable anticancer abilities under single laser source\nirradiation, benefiting from the NIR-II fluorescence/CT/MR multimodal\nimaging-guided photothermal/chemodynamic synergistic therapy. Overall,\nour strategy paves the way to explore other noninvasive cancer phototheranostics.