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

Thedevelopment of tumor microenvironment (TME)-activated nanoassemblieswhich can produce a photoacoustic (PA) signal and enhance the H2O2 level is critical to achieve accurate diagnosisand highly efficient chemodynamic therapy (CDT). In this study, wedeveloped 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 nanoassembliescan reduce tetrasulfide bonds and Cu2+ to sulfur ions andCu(+) in the TMG nanoassemblies, respectively, causing thebreakage of the tetrasulfide bond and the mesoporous structure collapse,releasing Cu+ ions and TiO2-x nanoparticles, and producing hydrogen sulfide gas, therebyachieving synergistic multimodal tumor treatment through TME-activatedNIR-II PA imaging and photothermal-enhanced gas starvation-primedCDT. Therefore, the TMG nanoassemblies form a smart nanoplatform thatcan serve as an excellent tumor diagnosis-treatment agent by playingan important role in imaging-guided precision diagnosis of cancerand efficient targeting treatment.

Automated summary

The development of tumor microenvironment-activated nanoassemblies that can produce a photoacoustic signal and enhance H2O2 level is crucial for accurate diagnosis and efficient chemodynamic therapy. In this study, nanoassemblies consisting of oxygen vacancy titanium dioxide, copper-sulfur-doped mesoporous organosilica, and glucose oxidase were developed. These nanoassemblies showed synergistic multimodal tumor treatment through TME-activated NIR-II PA imaging and photothermal-enhanced gas starvation-primed CDT, making them an excellent tumor diagnosis-treatment agent.