The study presents an innovative brain-targeted delivery system, named vinpocetine-derived ionizable-lipidoid nanoparticles (VIP), which enhances the brain biodistribution of drugs by regulating cerebral blood flow. VIP nanoparticles efficiently cross the blood-brain barrier (BBB), have high gene-loading capacity, and facilitate endosomal escape and intracellular transport. They are safe with minimal immunogenicity and exhibit potent pharmacologic brain-protective activity. The system was tested in male APP/PS1 mice, showing improved cerebral blood flow and enhanced cognitive performance. VIP also synergized with treatments for brain disorders, such as Alzheimer's disease (AD), brain tumors, and fungal meningitis. The study highlights the potential of VIP as a versatile and effective multifunctional carrier platform for drug delivery, particularly in addressing challenges associated with cerebrovascular disorders.The study presents an innovative brain-targeted delivery system, named vinpocetine-derived ionizable-lipidoid nanoparticles (VIP), which enhances the brain biodistribution of drugs by regulating cerebral blood flow. VIP nanoparticles efficiently cross the blood-brain barrier (BBB), have high gene-loading capacity, and facilitate endosomal escape and intracellular transport. They are safe with minimal immunogenicity and exhibit potent pharmacologic brain-protective activity. The system was tested in male APP/PS1 mice, showing improved cerebral blood flow and enhanced cognitive performance. VIP also synergized with treatments for brain disorders, such as Alzheimer's disease (AD), brain tumors, and fungal meningitis. The study highlights the potential of VIP as a versatile and effective multifunctional carrier platform for drug delivery, particularly in addressing challenges associated with cerebrovascular disorders.