Nanozyme-based therapeutic strategies for traumatic brain injury

Traumatic brain injury (TBI) is a leading cause of mortality and long-term neurological disability worldwide. Secondary injury, characterized by oxidative stress, neuroinflammation, blood brain barrier dysfunction, and lipid peroxidation, plays a crucial role in the progression of neurological damage following the initial mechanical insult. Despite substantial advances in clinical management, current therapeutic strategies remain largely supportive and have shown limited efficacy in preventing the complex pathological cascades associated with secondary brain injury. Nanozymes, a class of nanomaterials with intrinsic enzyme mimicking catalytic activities, have emerged as promising candidates for TBI therapy owing to their high stability, tunable catalytic performance, and sustained antioxidant capacity. Increasing evidence indicates that nanozymes can restore redox homeostasis, alleviate neuroinflammation, protect neurovascular integrity, and regulate lipid peroxidation related pathways. Representative preclinical studies have reported measurable benefits, including improved 30-day survival from 50% to 90% with oligomeric carbon nanozymes, preservation of post-traumatic cerebral perfusion by PEGylated oxidized activated charcoal nanozymes, and reduction of the ischemic area from 153 mm2 to 36 mm2 after repeated treatment with NIR-IIb fluorescent nanozymes. This review summarizes the pathological basis for nanozyme intervention in TBI, recent advances in nanozyme based therapeutic strategies, and the major challenges associated with clinical translation. Future perspectives on mechanism oriented catalytic nanomedicine for TBI treatment are also discussed.