L-type amino acid transporter 1 (LAT1)- targeting nanoparticles for antisense oligonucleotide delivery to the central nervous system

l-Type amino acid transporter 1 (LAT1)-specific ligands and polyion complexes are used as brain-specific targets to deliver RNA-based drugs across the blood-brain barrier. We characterized an LAT1-targeting antisense oligonucleotide (ASO)-encapsulated nanoparticle, Phe-NPs/ASO. A 25% density of phenylalanine effectively binds to the surface of LAT1-targeting NPs in the GL261-Luc cells, and Phe-NPs/ASO shows higher binding affinity compared to that without phenylalanine by cellular binding assay. To further characterize the blood-brain barrier-targeting effect and tissue distribution following a single-dose intravenous injection in mice, we performed