Blood-Brain Barrier-Targeting Nanoparticles: Biomaterial Properties and Biomedical Applications in Translational Neuroscience Evridiki Asimakidou, Justin Kok Soon Tan, Jialiu Zeng, and Chih Hung Lo review the role of nanoparticles (NPs) in enhancing drug delivery to the brain by targeting the blood-brain barrier (BBB). The BBB, composed of endothelial cells, pericytes, and astrocytes, restricts most molecules from entering the brain. NPs, due to their small size (10–100 nm), lipophilicity, and surface modifications, can cross the BBB through paracellular or transcellular transport. Factors such as size, shape, chemical composition, and surface charge influence NP penetration. Surface modifications, including conjugation with glucose, transferrin, insulin, aptamers, and peptides, enhance BBB targeting. NPs can also be coated with surfactants to improve their interaction with BBB receptors. In vitro and in vivo models, including transwell, 3D cell cultures, and microfluidic systems, are used to study NP penetration. Clinical detection methods like PET and SPECT assess NP entry into the brain. The review emphasizes the need for further research to optimize NPs for BBB targeting and their potential as therapeutic agents in neurological disorders. NPs offer a promising strategy for precise drug delivery to the brain.Blood-Brain Barrier-Targeting Nanoparticles: Biomaterial Properties and Biomedical Applications in Translational Neuroscience Evridiki Asimakidou, Justin Kok Soon Tan, Jialiu Zeng, and Chih Hung Lo review the role of nanoparticles (NPs) in enhancing drug delivery to the brain by targeting the blood-brain barrier (BBB). The BBB, composed of endothelial cells, pericytes, and astrocytes, restricts most molecules from entering the brain. NPs, due to their small size (10–100 nm), lipophilicity, and surface modifications, can cross the BBB through paracellular or transcellular transport. Factors such as size, shape, chemical composition, and surface charge influence NP penetration. Surface modifications, including conjugation with glucose, transferrin, insulin, aptamers, and peptides, enhance BBB targeting. NPs can also be coated with surfactants to improve their interaction with BBB receptors. In vitro and in vivo models, including transwell, 3D cell cultures, and microfluidic systems, are used to study NP penetration. Clinical detection methods like PET and SPECT assess NP entry into the brain. The review emphasizes the need for further research to optimize NPs for BBB targeting and their potential as therapeutic agents in neurological disorders. NPs offer a promising strategy for precise drug delivery to the brain.