Nanozyme-activating prodrug therapies: A review

Enzyme prodrug therapies (EPTs) have been intensively explored as attractive approaches to selective activation of systemically administered benign prodrugs by the exogenous enzymes or enzymes expressed at the desired target site, thus achieving localized, site-specific therapeutic effect. Many effective strategies (e.g., antibody-, viral-, gene-, as well as polymer-directed EPT) have been developed for enzyme localization to locally activate systemically administered benign prodrugs. Nevertheless, intrinsic limitations (e.g., complex intracellular environment and catalyst instability) make the practical application of EPT strategies a task that presents itself as highly challenging. As a promising alternative to natural enzyme, nanozyme has attracted substantial attention since its discovery in 2007, mainly due to the advantages of robust catalytic activity, high stability, low cost, and facile synthesis. Recently, nanozyme-activated prodrug strategies bring a new opportunity for targeted therapy, referred to as nanozyme-activating prodrug therapies. This review focuses on recently reported nanozyme-activated prodrug strategies, aiming to provide some new insights into the potential applications in site-specific drug synthesis.