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.

Keywords: Mn-etched dendritic mesoporous silicon; biodegradation; catalytic cascade; magnetic resonance imaging; synergistic therapy; tumor microenvironment responsive.