Trimodule Synergistic Janus Mesoporous Nanomotor for Photothermally-Enhanced Chemodynamic Therapy

Chemodynamic therapy (CDT) holds great promise for specific tumor ablation by <i>in situ</i> catalyzing endogenous H₂O₂ into highly reactive ·OH radicals that induce oxidative stress and trigger cell apoptosis. However, the intrinsically low H₂O₂ level in the tumor microenvironment (TME), together with the poor intratumoral accumulation and penetration of nanoparticles, severely restrict CDT efficacy. Herein, we report a trimodule, spatially asymmetric mesoporous nanomotor that integrates cascade catalysis, photothermal amplification, and self-propelled motion within a single Janus architecture to ameliorate these constraints. The GOx/Fe₃O₄@mSiO₂&mPDA (GOx: glucose oxidase; mSiO₂: mesoporous silica; mPDA: mesoporous polydopamine) nanomotors were constructed via an emulsion-induced oriented assembly strategy, featuring well-defined dual mesoporous domains of GOx/Fe₃O₄@mSiO₂ and mPDA with high surface area, robust near-infrared (NIR) photothermal conversion, and responsive motion under NIR irradiation. In mildly acidic conditions, the GOx/Fe₃O₄@mSiO₂ domain acts as a cascade catalytic subunit, where Fe₃O₄ catalyzes H₂O₂ to generate ·OH, while the surface-grafted GOx continuously converts glucose to gluconic acid and H₂O₂, thereby remodeling the TME into a favorable catalytic environment by acidifying it and replenishing the Fenton substrate. Simultaneously, the mPDA domain serves as a photothermal converter and propulsion engine unit. Its photothermal heating under 808 nm NIR irradiation not only drives active self-propelled motion, enabling enhanced penetration through the dense tumor matrix and deeper intratumoral distribution, but also elevates the local temperature, thereby accelerating the cascade catalytic kinetics and amplifying ·OH production. Benefiting from this trimodule synergy and motor-enhanced intratumoral transport, the nanomotors induce robust ·OH generation, amplified intracellular reactive oxygen species (ROS) levels, and pronounced 4T1 tumor cell ablation under NIR irradiation <i>in vitro</i> and achieve ∼99% tumor growth inhibition in 4T1 tumor-bearing mice.