Development and initial characterization of Ang-2 decorated exosome-liposome hybrid nanocarriers for BBB targeting capability: An evaluation of LRP-1 receptor mediated endocytosis

Central Nervous System (CNS) diseases, including Parkinson's, Alzheimer's, and brain tumors, are among the most challenging conditions to treat and are associated with high mortality rates. A significant obstacle in conventional treatment methods for CNS diseases is that many drugs struggle to penetrate the blood-brain barrier (BBB), which diminishes their effectiveness. The primary aim of the current study was to develop and characterize a hybrid nanocarrier composed of exosomes and liposomes to facilitate targeted drug delivery across the BBB for future CNS disease therapies. To achieve targeted uptake, we conjugated the exosome-liposome hybrid to the Angiopep-2 peptide (ANG-2), which has a specific affinity for the LRP-1 receptor, found on endothelial cells of the blood-brain barrier. Our results indicate that exosome-liposome hybrid nanoparticles exhibit significantly greater stability than exosomes alone. Moreover, the LRP-1 ligand-decorated exo-lipo hybrids effectively targeted U87 cells (a model cell line that expresses LRP-1) more efficiently than HEK293 (a cell line with low LRP-1 expression). Additionally, our findings demonstrated that these nanocarriers successfully evaded lysosomal degradation in U87 cells. We also assessed the barrier-crossing efficiency of the nanocarriers in vivo using zebrafish embryos.