Bioorthogonal nanozymes: an emerging strategy for disease therapy

Transition metal catalysts (TMCs), capable of performing bioorthogonal reactions, have been engineered to trigger the formation of bioactive molecules in a controlled manner for biomedical applications. However, the widespread use of TMCs based biorthogonal reactions in vivo is still largely limited owing to their toxicity, poor stability, and insufficient targeting properties. The emergence of nanozymes (nanomaterials with enzyme-like activity), especially bioorthogonal nanozymes that combine the bioorthogonal catalytic activity of TMCs, the physicochemical properties of nanomaterials, and the enzymatic properties of classical nanozymes potentially provide opportunities to address these challenges. Thus, they can be used as multifunctional catalytic platforms for disease treatment and will be far-reaching. In this review, we first briefly recall the classical TMC-based bioorthogonal reactions. Furthermore, this review highlights the diverse strategies for manufacturing bioorthogonal nanozymes and their potential for therapeutic applications, with the goal of facilitating bioorthogonal catalysis in the clinic. Finally, we present challenges and the prospects of bioorthogonal nanozymes in bioorthogonal chemistry.