Programming nanozyme identity for precision catalytic medicine by tailoring the bio-nano interface

The clinical translation of nanozymes faces substantial challenges, as their therapeutic efficacy in vivo is often significantly diminished by multiple physiological barriers and complex bio-nano interfacial interactions. To address these issues systematically, this review proposes an active "nanozyme identity programming" paradigm. Through rational design, this approach enables nanozymes to sequentially overcome biological barriers, thereby accelerating their clinical translation. We begin by systematically outlining the in vivo physiological roles and structural features of these barriers. We then examine how nanozymes can be functionally programmed at key hierarchical levels to acquire: (1) a "stealth identity" for prolonged circulation, (2) a "targeting identity" for precise lesion accumulation, and (3) a "microenvironment-responsive identity" for spatiotemporally controlled activation. Furthermore, we highlight the crucial roles of "bioinspired design" and artificial intelligence as powerful tools for integrating these functions and enabling the de novo design of intelligent nanozymes. Integrating this "identity programming" framework with the "nanozyme-interface-performance-application" research pipeline has shown great promise in developing advanced therapeutics for various pathological conditions, including inflammatory diseases, neurological disorders, cancers, and bacterial infections. Finally, we discuss the prospects, challenges, and opportunities of this paradigm in advancing nanozymes from functional materials toward precise nanomedicines and successful clinical translation.