Title:Accessing Targeted Nanoparticles to the Brain: The Vascular Route
Volume: 21
Issue: 36
Author(s): A. Burkhart, M. Azizi, M.S. Thomsen, L.B. Thomsen and T. Moos
Affiliation:
关键词:
基膜,血脑屏障,胞吞作用,纳米粒子,神经退行性变,OX26,转胞吞作用,转铁蛋白
摘要: The blood-brain barrier (BBB), formed by brain capillary endothelial cells, prevents the entry of several drug
molecules to the brain, especially molecules hydrophilic in nature. Advanced drug carriers like nanoparticles share the potential
to allow entry of therapeutic proteins and genetic molecules into the central nervous system (CNS). Taking a targeting
approach by conjugating molecules acting as ligands or monoclonal antibodies with affinity for proteins expressed
on the luminal side of brain capillary endothelial cells, the nanoparticles can be designed to enable transport into the brain
endothelium, or perhaps even through the endothelium leading to blood to brain transport. Currently, the iron-binding protein
transferrin or antibodies raised against the transferrin receptor denote the most feasible molecule for targeting purposes
at the BBB. This manuscript reviews the targetability of nanoparticles to the brain capillary endothelial cells, how
nanocarriers may enter and transfer through the brain endothelium, and how likely restraints denoted by the threedimensional
mesh of the extracellular proteins forming the brain capillary basement membrane challenge the possibilities
for enabling transport of large molecules through the BBB encapsulated in nanoparticles.