Qing Gao, Shuang Liu, Zhenzhen Guo, Didar Baimanov, Mingli Chen, Liming Wang
Precise control of catalytic activity in complex biological environments remains a fundamental challenge in biomedicine and nanotechnology. Nanozymes, engineered nanomaterials with enzyme-like catalytic properties, offer a promising solution, combining the robustness and tunability of inorganic materials with the functional sophistication of natural enzymes. However, their performance in vivo is profoundly influenced by dynamic interactions at biological interfaces, which govern catalytic efficiency, biodistribution, biocompatibility, and safety. In this review, we comprehensively examine the nanozyme−bio interface from two perspectives: Naturally formed interfaces have been formed, as well as artificially engineered interfaces. We elucidate how the biomolecular corona and artificial surface chemistry shape the nanozyme activity, behavior, and therapeutic outcomes. We further discuss emerging analytical technologies enabling real-time, high-resolution characterization of these interactions, alongside critical challenges hindering clinical translation. By integrating current insights and future perspectives, this work aims to advance the rational design of nanozymes with enhanced specificity, efficacy, and biocompatibility for transformative biomedical applications.