Metal-Based Nanozymes with Multienzyme-Like Activities as Therapeutic Candidates: Applications, Mechanisms, and Optimization Strategy

Most nanozymes in development for medical applications only exhibit single-enzyme-like activity, and are thus limited by insufficient catalytic activity and dysfunctionality in complex pathological microenvironments. To overcome the impediments of limited substrate availabilities and concentrations, some metal-based nanozymes may mimic two or more activities of natural enzymes to catalyze cascade reactions or to catalyze multiple substrates simultaneously, thereby amplifying catalysis. Metal-based nanozymes with multienzyme-like activities (MNMs) may adapt to dissimilar catalytic conditions to exert different enzyme-like effects. These multienzyme-like activities can synergize to realize self-provision of the substrate, in which upstream catalysts produce substrates for downstream catalytic reactions to overcome the limitation of insufficient substrates in the microenvironment. Consequently, MNMs exert more potent antitumor, antibacterial, and anti-inflammatory effects in preclinical models. This review summarizes the cellular effects and underlying mechanisms of MNMs. Their potential medical utility and optimization strategy from the perspective of clinical requirements are also discussed, with the aim to provide a theoretical reference for the design, development, and therapeutic application of their catalytic effects.

Automated summary

Most nanozymes developed for medical applications lack sufficient catalytic activity and functionality in complex pathological microenvironments due to their single-enzyme-like activity. Metal-based nanozymes with multienzyme-like activities (MNMs) can mimic two or more activities of natural enzymes, effectively catalyzing cascade reactions or multiple substrates simultaneously. These MNMs can adapt to different catalytic conditions, producing substrates for downstream catalytic reactions and overcoming the limitation of insufficient substrates in the microenvironment. As a result, MNMs have stronger antitumor, antibacterial, and anti-inflammatory effects in preclinical models. This review summarizes the cellular effects and underlying mechanisms of MNMs, and discusses their potential medical utility and optimization strategy for clinical applications, providing a theoretical reference for the design, development, and therapeutic application of their catalytic effects.