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 H2O2 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 (TiO2-x) surface-constructed copper, sulfur-doped mesoporous organosilica and glucose oxidase (TiO2-x@Cu,S-MONs@GOx, hereafter TMG). We found that highly abundant glutathione (GSH) in the TME nanoassemblies can reduce tetrasulfide bonds and Cu2+ 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 TiO2-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.