Reimagining Brain Drug Delivery: Mechanistic and Translational Advances in Carbon Nanotube Nanomedicine

Neurological and neurodegenerative disorders (NDDs) present ongoing therapeutic challenges attributed to the structural complexity of the central nervous system (CNS) and the restrictive properties of the blood-brain barrier (BBB), which inhibit the effective penetration of most drugs into the brain. Thus, carbon nanotubes (CNTs) possess a high aspect ratio, tunable surface chemistry, and exceptional electrical and mechanical properties, establishing them as versatile nanoplatforms that can address significant challenges in CNS drug delivery. Despite the exploration of various nanocarriers, a significant gap persists in the comprehensive understanding of the convergence of CNT structure, functionalization, mechanistic transport pathways, and safety-by-design strategies for translational neurological applications. This review synthesizes recent advancements in CNT engineering, mechanisms of BBB traversal, cell-specific targeting, and intracellular trafficking, as well as insights into CNT-induced neurotoxicity and clearance pathways. Further, the review emphasizes therapeutic advancements in CNT-mediated interventions for Alzheimer's disease (AD), Parkinson's disease (PD), brain tumors, stroke, and epilepsy, focusing on multifunctional applications in drug delivery, neuroregeneration, immunomodulation, neuromodulation, theranostic, and biosensing. Additionally, it assesses preclinical results, safety factors, regulatory challenges, and the growing influence of artificial intelligence (AI)-driven design in enhancing nanoscale behavior, functionalization, and biocompatibility. Lastly, the current review integrates technological innovations with mechanistic toxicology and translational challenges, establishing CNTs as promising neuro-nanomedicine platforms that may effectively address unmet clinical needs in CNS disorders. Trial Registration: ClinicalTrials.gov: NCT04495634, NCT02873585, NCT01246336, NCT07034248, NCT07034248.