Crossing the Blood–Brain Barrier with Molecularly Imprinted Polymeric Nanocarriers: An Emerging Frontier in Brain Disease Therapy

Molecularly imprinted polymeric nanocarriers (nanoMIPs) offer robust, antibody‐mimetic platforms to overcome the blood‐brain barrier. The article surveys nanoMIP design and ligand‐directed surface engineering that harness receptor‐mediated transcytosis, and highlights therapeutic and diagnostic applications in neurodegeneration, brain tumors and central nervous system infections, while addressing key challenges in biocompatibility, large‐scale manufacture and regulatory translation. Abstract The ability to permeate the blood‒brain barrier (BBB) remains a major challenge in treating neurological disorders. Molecularly imprinted polymeric nanocarriers (nanoMIPs) are emerging as versatile platforms that integrate antibody‐mimetic recognition with exceptional stability, tunable physicochemical properties, and controlled drug release. This review summarizes recent advances in nanoMIP design, including template selection, polymerization strategies, and surface modifications, and explores their potential for targeted brain delivery. Particular emphasis is placed on surface engineering approaches, such as functionalization with apolipoprotein E (ApoE), transferrin, and angiopep‐2 ligands, which exploit receptor‐mediated transcytosis (RMT) to increase BBB permeation and drug accumulation in pathological brain regions. The therapeutic and diagnostic applications of nanoMIPs in neurodegeneration, brain tumors, and CNS infections are also highlighted. Finally, current limitations and future perspectives are discussed, including biocompatibility, large‐scale production, and regulatory considerations, positioning nanoMIPs as a next‐generation platform for overcoming BBB‐associated barriers, and advancing precision brain therapeutics. Molecularly imprinted polymeric nanocarriers (nanoMIPs) offer robust, antibody-mimetic platforms to overcome the blood-brain barrier. The article surveys nanoMIP design and ligand-directed surface engineering that harness receptor-mediated transcytosis, and highlights therapeutic and diagnostic applications in neurodegeneration, brain tumors and central nervous system infections, while addressing key challenges in biocompatibility, large-scale manufacture and regulatory translation. Abstract The ability to permeate the blood‒brain barrier (BBB) remains a major challenge in treating neurological disorders. Molecularly imprinted polymeric nanocarriers (nanoMIPs) are emerging as versatile platforms that integrate antibody-mimetic recognition with exceptional stability, tunable physicochemical properties, and controlled drug release. This review summarizes recent advances in nanoMIP design, including template selection, polymerization strategies, and surface modifications, and explores their potential for targeted brain delivery. Particular emphasis is placed on surface engineering approaches, such as functionalization with apolipoprotein E (ApoE), transferrin, and angiopep-2 ligands, which exploit receptor-mediated transcytosis (RMT) to increase BBB permeation and drug accumulation in pathological brain regions. The therapeutic and diagnostic applications of nanoMIPs in neurodegeneration, brain tumors, and CNS infections are also highlighted. Finally, current limitations and future perspectives are discussed, including biocompatibility, large-scale production, and regulatory considerations, positioning nanoMIPs as a next-generation platform for overcoming BBB-associated barriers, and advancing precision brain therapeutics. Advanced Science, EarlyView.