A glutathione depletion-activated near-infrared nanoprobe based on valence engineering of molybdenum and cerium for boosting tumor photoacoustic diagnosis and cascade therapy

Photoacoustic (PA) imaging-guided tumor treatment can realize the accurate diagnosis of cancers and the visual monitoring of the treatment process. For this purpose, a tumor microenvironment (TME)-activated cerium-doped polyoxometalate (Ce-POM) nanoprobe was developed for PA imaging-guided diagnosis and boosted cascade therapy. Mo 6+ in the Ce-POM structure reacts with glutathione (GSH), which is enriched in the TME, resulting in a broad near-infrared absorption peak (650–1300 nm) for tumor-specific PA imaging. In addition, Ce-POM exhibits peroxidase-like activity, which can catalyze the Fenton-like reaction of Ce 3+ with hydrogen peroxide (H 2 O 2 ) in the TME to form hydroxyl radicals ( · OH) for chemodynamic therapy (CDT). Ce-POM reduced antioxidative capacity by depleting GSH in tumor cells, and 808-nm laser irradiation promoted its reaction with H 2 O 2 to generate abundant · OH, thus improving the CDT efficacy. The GSH consumption in tumor tissues also enhanced the photothermal conversion capacity of Ce-POM, leading to a rapid temperature rise to more than 50°C at tumor sites, realizing efficient photothermal treatment. The Ce-POM nanoprobe enabled PA visualization and effective cascade therapy in 4T1 tumor-bearing mice, providing a theranostic platform for PA imaging-guided tumor ablation.