Biodegradable Silica‐Based Nanotheranostics for Precise MRI/NIR‐II Fluorescence Imaging and Self‐Reinforcing Antitumor Therapy

Abstract Multi‐modality cancer diagnosis techniques based on the second near‐infrared window fluorescence (NIR‐II FL, 1000–1700 nm) imaging have become the focus of research attention. For such multimodality probes, how to take advantage of the tumor microenvironments (TME) characteristics to better image diseases and combine efficient therapeutics to achieve theranostics is still a big challenge. Herein, a novel TME‐activated nanosystem (FMSN‐MnO 2 ‐BCQ) employing degradable silica‐based nanoplatform is designed, adjusting the ratio of intratumoral hydrogen peroxide (H 2 O 2 )/glutathione (GSH) for magnetic resonance imaging (MRI)/NIR‐II FL imaging and self‐reinforcing chemodynamic therapy (CDT). Innovative bovine serum albumin (BSA)‐modified fusiform‐like mesoporous silica nanoparticles (FMSN) is fabricated as a carrier for NIR‐II small molecule (CQ4T) and MRI reporter MnO 2 . Remarkably, the BSA modification helped to achieve the dual‐functions of high biocompatibility and enhance NIR‐II fluorescence. The FMSN‐MnO 2 ‐BCQ with FMSN framework featuring a stepwise degradability in tumor interior released MnO 2 and BCQ nanoparticles. Through the specific degradation of MnO 2 by the TME, the produced Mn 2+ ions are effectively exerted Fenton‐like activity to generate hydroxyl radical (•OH) from endogenous H 2 O 2 to eradicate tumor cells. More importantly, the GSH depletion due to the synergistic effect of tetrasulfide bond and MnO 2 in turn induced the oxidative cytotoxicity for self‐reinforcing CDT.