Tumor Microenvironment‐Responsive Mesoporous MnO₂‐Coated Upconversion Nanoplatform for Self‐Enhanced Tumor Theranostics

Abstract The insufficient blood flow and oxygen supply in solid tumor cause hypoxia, which leads to low sensitivity of tumorous cells and thus causing poor treatment outcome. Here, mesoporous manganese dioxide (mMnO 2 ) with ultrasensitive biodegradability in a tumor microenvironment (TME) is grown on upconversion photodynamic nanoparticles for not only TME‐enhanced bioimaging and drug release, but also for relieving tumor hypoxia, thereby markedly improving photodynamic therapy (PDT). In this nanoplatform, mesoporous silica coated upconversion nanoparticles (UCNPs@mSiO 2 ) with covalently loaded chlorin e6 are obtained as near‐infrared light mediated PDT agents, and then a mMnO 2 shell is grown via a facile ultrasonic way. Because of its unique mesoporous structure, the obtained nanoplatform postmodified with polyethylene glycol can load the chemotherapeutic drug of doxorubicin (DOX). When used for antitumor application, the mMnO 2 degrades rapidly within the TME, releasing Mn 2+ ions, which couple with trimodal (upconversion luminescence, computed tomography (CT), and magnetic resonance imaging) imaging of UCNPs to perform a self‐enhanced imaging. Significantly, the degradation of mMnO 2 shell brings an efficient DOX release, and relieve tumor hypoxia by simultaneously inducing decomposition of tumor endogenous H 2 O 2 and reduction of glutathione, thus achieving a highly potent chemo‐photodynamic therapy.