Platinum nanozymes pursue cellular redox homeostasis: playing dual roles as pro-oxidants and antioxidants

Cellular redox homeostasis, essential for physiological integrity, is disrupted by pathological oxidative stress from imbalanced reactive oxygen species (ROS) metabolism, which is a central driver of degenerative, inflammatory diseases and tumors. Platinum (Pt) nanozymes have emerged as promising therapeutic agents capable of mimicking both antioxidative and pro-oxidative enzymatic activities, owing to their partially filled d-orbitals and accessible multivalent states, thereby enabling precise regulation of cellular redox homeostasis. From a chemical perspective, this “smart switching” capability originates from dynamic changes in microenvironmental cues, such as nanozyme concentration, H2O2 levels, and pH, which alter the dominant enzymatic activity, thereby achieving dual-mode ROS regulation by toggling between antioxidative and pro-oxidative states. This adaptive duality directly addresses a fundamental therapeutic dilemma: selectively restoring redox homeostasis in diseased tissue while sparing healthy cells. Therefore, this review systematically elaborates, for the first time, an integrated framework encompassing the intrinsic redox enzymatic activities of Pt nanozymes and their “smart switching” mechanisms, offering a cross-disciplinary perspective spanning material design to disease applications. First, we delineate evolving research trends and recent advancements in Pt nanozymes for redox homeostasis regulation through a bibliometric analysis of 512 publications from the Web of Science. Subsequently, we elucidate the catalytic mechanisms governing their tunable redox enzymatic activities and discuss versatile engineering strategies for tailoring antioxidant/pro-oxidant functionalities to enable precision therapeutic interventions. Finally, we critically evaluate current translational challenges and present future perspectives on addressing multifaceted disease pathologies using Pt nanozymes. 1. A systematic review of the four key redox enzymatic activities of Pt nanozymes and their catalytic mechanisms is provided. 2. Strategies based on size, morphology, component doping, and surface modification to enhance the activity of Pt nanozymes are proposed. 3. The application progress and challenges of Pt nanozymes in over ten disease models, including inflammation, tumors, and neurodegenerative diseases, are summarized.