Spatiotemporally Controlled Photothermal-Enhanced Cascade Nanoreactor for Efficient Antitumor Therapy through Tumor Microenvironment Modulation

The primary challenges for nanozyme-mediated tumor catalytic therapy are the insufficient catalytic activity of nanozymes and inadequate endogenous hydrogen peroxide (H2O2) levels in the tumor microenvironment (TME). To address these challenges, FeMOF/Pt/GOx (FMPG), a TME-responsive cascade nanoreactor, was designed for photothermal-cascade catalytic antitumor therapy. FMPG comprises MIL-100(Fe), an iron-based metal-organic framework material, loaded with ultrasmall platinum nanoparticles (Pt NPs) and glucose oxidase (GOx). Within the TME, FMPG degrades in the presence of high phosphate concentrations, releasing GOx, Fe2+, and Pt NPs. GOx consumes glucose, reducing ATP levels in cells and inducing a starvation state in tumor cells. Subsequently, the H2O2 produced by GOx and overexpressed in tumor cells reacts with Fe2+ to generate hydroxyl radicals, facilitating cascade catalytic therapy. The Pt NPs exhibit catalase-like activity and catalyze the production of oxygen from H2O2, further enhancing starvation. Under 808 nm laser irradiation, the as-prepared composites generate localized heat, enabling effective photothermal therapy. This nanoreactor demonstrates efficient tumor inhibition by in situ consumption and production of compounds, promoting the development of precise synergetic cancer therapies with spatiotemporal controllability.