Overcoming blood-brain barrier via nanobiotechnology

Abstract

Central nervous system diseases, including neurodegenerative diseases and brain malignancies, remain a critical medical challenge. Nanoparticle-enabled therapy and diagnosis have demonstrated promises to address brain diseases. However, one of the physical barriers is the blood-brain barrier (BBB), which largely restricts nanoparticle transport to the brain. To address this issue, many strategies have been developed. One of the important strategies is binding nanoparticles to a targeting ligand (e.g., transporter proteins) that deliver nanoparticles to brain tissues via transcytosis. However, this approach is limited by the poor specificity of transporter proteins, and none of these proteins are unique to the brain, so this can lead to undesirable efficiency in crossing the blood-brain barrier. In this thesis, I use brain microvascular endothelial cell membranes that are homologous to those in the BBB to coat iron oxide nanoparticles, preserving the complex antigenic information on the cell membranes and achieving biofunctionalization of nanomaterials. I demonstrated that the cell membrane-coated iron oxide nanoparticles have a core-shell structure, good biocompatibility, and stability. By using in vitro models, the cell membrane-coated iron oxide nanoparticle exhibited cell-specific targeting and BBB crossing efficiency.