The application discloses a
pathological blood-brain barrier targeting nano-preparation for treating Alzheimer's
disease and a preparation method thereof, and belongs to the technical field of biological
medicine. The nano-preparation takes nanoparticles assembled by an amphiphilic block
copolymer as a carrier, and is co-modified with RAP peptides and RGD peptides on the surface. The RAP peptides can specifically recognize and bind to the RAGE
receptor which is highly expressed by vascular endothelial cells in a
pathological state, so that precise targeting is realized, and the RAP peptides also have the activity of blocking the RAGE-AB
pathological pathway. The RGD peptides serve as an
integrin binding motif, can significantly enhance the
endocytosis efficiency of the nanoparticles through the interaction with the
cell surface
integrin receptor, and promote the transportation of the nanoparticles to lysosomes after
endocytosis. Through the synergistic effect of the two ligands, the nanoparticles can not only be efficiently targeted to the diseased brain
vascular endothelium expressing RAGE, but also be effectively internalized and guided to lysosomes, so that the
targeted drug delivery is realized, the degradation of the RAGE
protein is enhanced by means of the
lysosome pathway, and the active intervention on the key pathological pathway is realized.