From the blood to the central nervous system: A nanoparticle's journey through the blood–brain barrier by transcytosis

Designing nanoparticles that effectively enter the central nervous system (CNS) rapidly and without alteration is one of the major challenges in the use of nanotechnology for the brain. In this chapter, we explore the process of transcytosis, a receptor-mediated transport pathway that permits endogenous macromolecules to enter the CNS by crossing the blood–brain barrier. Transcytosis across the blood–brain barrier involves a number of distinct stages, including receptor binding, endocytosis into a transport vesicle, trafficking of the vesicle to the opposite side of the cell, and finally exocytosis and release of cargo. For each stage, we discuss the current knowledge on biological, physiological, and physical factors that influence nanoparticle transit through that stage of transcytosis, with implications for nanoparticle design. Finally, we look at the current progress in designing nanoparticles that exploit transcytosis for CNS delivery.