Chemodynamic therapy (CDT) holds great promise for specific tumor ablation by in situ 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 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 in vitro and achieve ∼99% tumor growth inhibition in 4T1 tumor-bearing mice.
Ma et al. (Thu,) studied this question.