Synthetic Polymer Nanoparticles Functionalized with Different Ligands for Receptor-Mediated Transcytosis across the Blood-Brain Barrier

Polymeric nanoparticles have been investigated as biocompatible and promising nanocarriers to deliver drugs across the blood-brain barrier (BBB). However, most of the polymeric nanoparticles cannot be observed without attaching them with fluorescent dyes. Generally complex synthesis process is required to attach fluorescent dye tracing molecules with drug carrier nanoparticles. In this paper, we synthesized a novel fluorescent polymer based on poly [Triphenylamine-4-vinyl-(P-methoxy-benzene)] (TEB). This polymeric nanoparticle was prepared from TEB polymer through coprecipitation. Furthermore, three types of ligands, transferrin (TfR), lactoferrin (LfR), and lipoprotein (LRP), were covalently attached on the nanoparticle surface to improve the BBB transport efficiency. All the prepared TEB-based nanoparticles were biocompatible, exhibited excellent fluorescence properties, and could be observed in vivo. The transcellular transportation of these TEB-based nanoparticles across the BBB was evaluated by observing the fluorescent intensity. The translocation study was performed in an in vitro BBB model that were constructed based on mouse cerebral endothelial cells (bEnd.3). The results showed that ligand-coated TEB nanoparticles can be transported across BBB with high efficiencies (up to 29.0%). This is the first time the fluorescent TEB nanoparticles were applied as nanocarriers for transport across the BBB. Such fluorescent polymeric nanoparticles have potential applications in brain imaging or drug delivery.