Reductant‐Free Synthesis of MnO2 Nanosheet‐Decorated Hybrid Nanoplatform for Magnetic Resonance Imaging‐Monitored Tumor Microenvironment‐Responsive Chemodynamic Therapy and Near‐Infrared‐Mediated Photodynamic Therapy

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Recently, the therapeutic efficacy of reactive oxygen species (ROS)‐mediated photodynamic therapy (PDT) involving laser irradiation or chemodynamic therapy (CDT) has been limited by low laser penetration depth and insufficient O2 supply in PDT and modest ROS production in CDT. To address these, a facile “reductant‐free reduction” strategy is developed to construct a smart tumor microenvironment (TME)/near‐infrared dual‐responsive hybrid nanoplatform, consisting of up‐conversion nanoparticles (UCNPs) and photosensitizer chlorin e6 (Ce6) in the micellar core and MnO2 nanosheets on the organosilica shell, via the self‐assembly of block copolymer and followed by a sol−gel process. The conversion capability of UCNPs improves laser penetration of visible light for initiating the photodynamic process. The degradation of MnO2 nanosheets in the TME rich in acid H2O2 achieves continuous O2 supply for enhanced PDT. Following degradation of MnO2, the endogenous antioxidant glutathione (GSH) is significantly depleted and hydroxyl radicals (•OH) are simultaneously produced though CDT, together inducing massive production of ROS. More importantly, Mn2+ released from MnO2 decomposition serves as a T1‐weighted MR contrast agent, providing an easy monitor for the CDT process. This hybrid MnO2/Ce6@UPOMs nanoplatform could be used for MRI‐monitored tumor therapy of TME‐responsive CDT and NIR‐mediated PDT.