Rapid Decomposition and Catalytic Cascade Nanoplatforms Based on Enzymes and Mn-Etched Dendritic Mesoporous Silicon for MRI-Guided Synergistic Therapy

Abstract

The endogenous tumor microenvironment (TME) can signally influence the therapeutic effects of cancer, so it is necessary to explore effective synergistic therapeutic strategies based on changing of the TME. Here, a catalytic cascade nanoplatform based on manganese (Mn)-etched dendritic mesoporous silicon nanoparticles (designated as DMMnSiO3 NPs) loaded with indocyanine green (ICG) and natural glucose oxidase (GOD) is established (designated as DIG nanocomposites). As the Mn-O bonds in DMMnSiO3 NPs are susceptive to mildly acidic and reducing environments, the DIG nanocomposites can be rapidly decomposed because of the biodegradation of DMMnSiO3 NPs once internalized into the tumor by the consumption of glutathione (GSH) in TME to weaken the antioxidant capability of the tumors. The released Mn2+ could catalyze endogenous hydrogen peroxide (H2O2) to generate oxygen (O2) to relieve the hypoxia in TME. The generation of O2 may promote the catalyzed oxidation of glucose by GOD, which will cut off nutrient supplies, accompanied by the regeneration of H2O2. The regenerated H2O2 could be sequentially catalyzed by Mn2+ to compensate for the consumed O2, and thus, the catalytic cascade process between Mn2+ and GOD was set up. As a result, a synergistic therapeutic strategy based on T1-weighted magnetic resonance imaging (MRI) of Mn2+, starvation therapy by O2-compensation enhanced catalyzing glucose, dual-model (GSH consumption and O2 compensation) enhanced photodynamic therapy, and effective photothermal therapy of ICG (η = 23.8%) under 808 nm laser irradiation has been successfully established.