Next-Generation Renal Targeting Nanozymes for Acute Kidney Injury: Engineering Catalytic Therapeutics for Oxidative Stress, Immune Regulation, and Renal Repair

Acute kidney injury (AKI) is a multifactorial clinical syndrome associated with rapid deterioration of renal function and involves interconnected processes including oxidative stress, mitochondrial dysfunction, inflammation, endothelial injury, programmed cell death, immune dysregulation and maladaptive repair. Current management is predominantly supportive and lacks effective pharmacological strategies that simultaneously address these pathological mechanisms. Renal-targeting nanozymes have emerged as promising catalytic nanotherapeutics that combine enzyme-mimicking activity with the tunable properties of nanomaterials. This review critically examines the engineering and therapeutic potential of renal-targeting nanozymes for AKI, focusing on nanozyme platforms, catalytic properties, renal-targeting strategies, and mechanisms underlying their antioxidant,immunomodulatory, cytoprotective, and regenerative effects. Preclinical evidence from experimental AKI models is discussed with emphasis on therapeutic outcomes, comparative performance, and current limitations. Particular attention is given to challenges involving renal accumulation, biodistribution, long-term biosafety, biodegradability,reproducibility, manufacturing scalability, and regulatory requirements. Emerging strategies, including biomimetic and biodegradable nanozymes, stimulus-responsive systems, theranostic platforms, and artificial intelligence-assisted nanozyme design, are also considered. Overall, renal-targeting nanozymes represent a promising multifunctional approach for addressing the complex pathophysiology of AKI. However, standardized preclinical evaluation, scalable manufacturing, comprehensive safety assessment, appropriate regulatory frameworks, and well-designed clinical studies remain essential for translating these catalytic nanotherapeutics into clinically viable precision therapies.