Spatiotemporally\nControlled Photothermal-Enhanced\nCascade Nanoreactor for Efficient Antitumor Therapy through Tumor\nMicroenvironment Modulation

The primary challenges for nanozyme-mediated tumor catalytic\ntherapy\nare the insufficient catalytic activity of nanozymes and inadequate\nendogenous hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>) levels in\nthe tumor microenvironment (TME). To address these challenges, FeMOF/Pt/GOx\n(FMPG), a TME-responsive cascade nanoreactor, was designed for photothermal-cascade\ncatalytic antitumor therapy. FMPG comprises MIL-100(Fe), an iron-based\nmetal–organic framework material, loaded with ultrasmall platinum\nnanoparticles (Pt NPs) and glucose oxidase (GOx). Within the TME,\nFMPG degrades in the presence of high phosphate concentrations, releasing\nGOx, Fe<sup>2+</sup>, and Pt NPs. GOx consumes glucose, reducing ATP\nlevels in cells and inducing a starvation state in tumor cells. Subsequently,\nthe H<sub>2</sub>O<sub>2</sub> produced by GOx and overexpressed in\ntumor cells reacts with Fe<sup>2+</sup> to generate hydroxyl radicals,\nfacilitating cascade catalytic therapy. The Pt NPs exhibit catalase-like\nactivity and catalyze the production of oxygen from H<sub>2</sub>O<sub>2</sub>, further enhancing starvation. Under 808 nm laser irradiation,\nthe as-prepared composites generate localized heat, enabling effective\nphotothermal therapy. This nanoreactor demonstrates efficient tumor\ninhibition by in situ consumption and production of compounds, promoting\nthe development of precise synergetic cancer therapies with spatiotemporal\ncontrollability.