Coordination Chemistry Reviews, 13 August, 2025, DOI：https://doi.org/10.1016/j.ccr.2025.217033

Stimuli-Responsive Nanozymes in Imaging and Therapy of Critical Diseases

Xiaowan Fan, Xiaofei Fu, Shuai Han, Dongnan Sun, Runze Wang, Mingzhen Zhang, Wei Jiang, Kelong Fan

Abstract

Conventional therapies for critical illnesses are often hampered by inadequate efficacy and pronounced systemic toxicity, severely restricting their clinical prospects. To overcome these hurdles, stimuli-responsive drug-delivery systems (DDSs) have seized the spotlight for their ability to discriminate pathological fingerprints unique to diseased tissues, thereby unleashing exquisitely targeted therapy. Among these advanced DDSs, nanozymes, which are nanomaterials with intrinsic enzyme-mimetic activities, have emerged as a particularly promising modality. The unique attributes of these materials, including their catalytic functionality, tunable surface properties, and physiological stability, make them versatile platforms for biomedical applications. By engineering nanozymes to respond to specific endogenous or exogenous stimuli (e.g., pH, redox state, temperature, or enzymatic activity), these nanomaterials can facilitate site-specific drug release and real-time therapeutic monitoring. This targeted approach not only optimizes therapeutic efficacy but also significantly reduces off-target side effects, rendering nanozymes highly suitable for the treatment of critical diseases where precision is of utmost importance. This review provides an in-depth overview of recent advancements in the design of stimuli-responsive nanozymes for biomedical applications, including disease diagnosis, targeted therapy, and theranostics. Special attention has been given to the integration of catalytic mechanisms with stimuli-responsive elements, which collectively enhance selectivity and efficacy in the treatment of critical diseases. Despite notable progress, several key challenges persist, including the need to improve catalytic specificity, ensure biosafety, and develop scalable and reproducible synthetic methods. Ongoing efforts in material innovation, structural refinement, and mechanistic elucidation are essential to drive the clinical translation of nanozymes. Given the substantial burden that critical diseases impose on global health, the development of next-generation nanozyme-based therapies represents a transformative opportunity to improve patient outcomes and enhance the overall efficacy of treatment strategies.

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