Delivery of nanoparticle-complexed drugs across the vascular endothelial barrier via caveolae

The endothelial cell monolayer lining the vessel wall forms a size-selective, semi-permeable barrier between the blood and tissue that must be crossed by blood borne therapeutic agents to reach diseased extravascular tissue. Nanoparticles engineered to carry drugs present an opportunity to enhance the specificity and efficacy of drug delivery. Therefore, an understanding of how these engineered nanoparticles are transported across the vessel wall will help us to more fully exploit this powerful therapeutic technology. Vascular endothelial cells are rich in caveolae, cell surface invaginations 50-100 nm in diameter that mediate endocytosis of lipids, proteins, and viruses. Caveolar invaginations pinch off to form intracellular vesicles that can transport cargo across the cell and release the cargo into the extravascular space via exocytosis. Here, we will review the current concepts and state of development for delivering engineered nanoparticles across the endothelium via the caveolae-mediated pathway.