H₂O₂ Self-Supply and Glutathione Depletion Engineering Nanoassemblies for NIR-II Photoacoustic Imaging of Tumor Tissues and Photothermal-Enhanced Gas Starvation-Primed Chemodynamic Therapy

The development of tumor microenvironment (TME)-activated nanoassemblies which can produce a photoacoustic (PA) signal and enhance the H 2 O 2 level is critical to achieve accurate diagnosis and highly efficient chemodynamic therapy (CDT). In this study, we developed nanoassemblies consisting of oxygen vacancy titanium dioxide (TiO 2– x ) surface-constructed copper, sulfur-doped mesoporous organosilica and glucose oxidase (TiO 2– x @Cu,S-MONs@GOx, hereafter TMG). We found that highly abundant glutathione (GSH) in the TME nanoassemblies can reduce tetrasulfide bonds and Cu 2+ to sulfur ions and Cu + in the TMG nanoassemblies, respectively, causing the breakage of the tetrasulfide bond and the mesoporous structure collapse, releasing Cu + ions and TiO 2– x nanoparticles, and producing hydrogen sulfide gas, thereby achieving synergistic multimodal tumor treatment through TME-activated NIR-II PA imaging and photothermal-enhanced gas starvation-primed CDT. Therefore, the TMG nanoassemblies form a smart nanoplatform that can serve as an excellent tumor diagnosis-treatment agent by playing an important role in imaging-guided precision diagnosis of cancer and efficient targeting treatment.