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

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.