Nanoparticle targeting strategies for traumatic brain injury

Abstract Nanoparticle (NP)-based drug delivery systems hold immense potential for targeted therapy and diagnosis of neurological disorders, overcoming the limitations of conventional treatment modalities. This review explores the design considerations and functionalization strategies of NPs for precise targeting of the brain and central nervous system. This review discusses the challenges associated with drug delivery to the brain, including the blood-brain barrier and the complex heterogeneity of traumatic brain injury. We also examine the physicochemical properties of NPs, emphasizing the role of size, shape, and surface characteristics in their interactions with biological barriers and cellular uptake mechanisms. The review concludes by exploring the options of targeting ligands designed to augment NP affinity and retention to specific brain regions or cell types. Various targeting ligands are discussed for their ability to mimic receptor-ligand interaction, and brain-specific extracellular matrix components. Strategies to mimic viral mechanisms to increase uptake are discussed. Finally, the emergence of antibody, antibody fragments, and antibody mimicking peptides are discussed as promising targeting strategies. By integrating insights from these scientific fields, this review provides an understanding of NP-based targeting strategies for personalized medicine approaches to neurological disorders. The design considerations discussed here pave the way for the development of NP platforms with enhanced therapeutic efficacy and minimized off-target effects, ultimately advancing the field of neural engineering.