Self-propelled enzymatic nanomotors for enhancing synergetic photodynamic and starvation therapy by self-accelerated cascade reactions

Abstract Enzyme-driven micro/nano-motors have emerged as promising self-propelled therapeutic nanosystems in biomedical field owing to good biocompatibility, versatility, and fuel bioavailability. Here, we synthesize a dual enzyme-functionalized core-shell nanomotor (designated as UTZCG) based on metal-organic framework nanoparticles for enhancing synergetic photodynamic therapy (PDT) and starvation therapy (ST). The modified glucose oxidase (GOx) catalyzes the decomposition of intracellular glucose, which starves cells and generates hydrogen peroxide (H2O2). Then, catalase-triggered decomposition of both endogenous and GOx-generated H2O2 provides propulsion force and enhances the diffusivity of the nanomotors by up to about 27%, which increases the cellular uptake of the therapeutic nanomotors. Meanwhile, the produced oxygen molecules not only promote singlet oxygen generation during near-infrared light-triggered PDT process, but also facilitate the GOx-triggered decomposition of glucose. Thus, the two enzymatic cascade reactions form a positive feedback for the whole nanomotor based therapeutic system, and greatly improve the efficacy of the synergetic PDT and ST.