O₂ self-sufficient and glutathione-depleted nanoplatform for amplifying phototherapy synergistic thermodynamic...

Tumor hypoxia and high levels of intracellular glutathione (GSH) significantly limit the efficacy of photodynamic therapy (PDT). In addition, a single PDT treatment strategy is relatively insufficient to eliminate tumor, further limiting its application in biomedicine. Therefore, we demonstrated an omnipotent nanoplatform based on 2,2'-azobis [2-(2 imidazolin-2-yl)propane] dihydrochloride (AIPH) loaded manganese dioxide (MnO₂) nanoflower (abbreviated as MnO₂-AIPH) with simultaneously self-supplying oxygen (O₂), depleting GSH, performing PDT, photothermal (PTT) and thermodynamic therapy (TDT) for boosting antitumor effects. By 808 nm near infrared (NIR) light irradiation, MnO₂-AIPH not only reveals highly toxic reactive oxygen species (ROS) generation and excellent photothermal conversion ability for PDT and PTT, but also generates alkyl radicals by decomposing AIPH for TDT simultaneously to eliminate tumor effectively. Once internalized into the tumor, MnO₂ will be degraded to Mn²⁺ which catalyzes endogenous hydrogen peroxide (H₂O₂) into O₂ for enhanced PDT. Moreover, MnO₂ can facilitate GSH oxidation to amplify oxidative stress, further enhancing ROS and alkyl radicals mediated cancer cell killing. In brief, this study provides a paradigm of antitumor efficiency amplification by the combination of sustained oxygen supply, potent GSH depletion, and phototherapy synergistic TDT.