The Design Strategies and Applications of Engineered Nanoparticles for Traumatic Brain Injury.

Traumatic brain injury (TBI) is a serious neurological condition. Because of its complex pathophysiological processes, direct treatment options are extremely limited. A key reason for this is the blood-brain barrier (BBB), which makes it difficult for conventional drug molecules to penetrate and maintain effective concentrations in brain tissue. In recent years, nanoparticles have garnered significant attention due to their unique biological properties, enhanced therapeutic effects, and low toxicity. By modifying the surface of nanoparticles with targeting ligands, their penetration capacity can be significantly enhanced, enabling directed delivery to the core injury area and substantially increasing their accumulation at the site of injury. Furthermore, functionally engineered nanoparticles can respond to specific signals in the TBI microenvironment, such as reactive oxygen species (ROS), enzymes, and pH changes, thereby enabling controlled drug release and significantly improving delivery efficiency. This review systematically summarizes the latest advances in engineered nanoparticles for TBI treatment from three perspectives: rational design, therapeutic strategies, and clinical translation.