title: Pathogen-inspired drug delivery to the central nervous system.
abstract: For as long as the human blood-brain barrier (BBB) has been evolving to exclude bloodborne agents from the central nervous system (CNS), pathogens have adopted a multitude of strategies to bypass it. Some pathogens, notably viruses and certain bacteria, enter the CNS in whole form, achieving direct physical passage through endothelial or neuronal cells to infect the brain. Other pathogens, including bacteria and multicellular eukaryotic organisms, secrete toxins that preferentially interact with specific cell types to exert a broad range of biological effects on peripheral and central neurons. In this review, we will discuss the directed mechanisms that viruses, bacteria, and the toxins secreted by higher order organisms use to enter the CNS. Our goal is to identify ligand-mediated strategies that could be used to improve the brain-specific delivery of engineered nanocarriers, including polymers, lipids, biologically sourced materials, and imaging agents.
authors.affiliation: Barrow Brain Tumor Research Center; Barrow Neurological Institute ; Phoenix, AZ USA.
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: McCall
authors.affiliation: Blue Ocean Biomanufacturing , Worcester, MA USA.
authors.forename: Joseph
authors.initials: J
authors.lastname: Cacaccio
authors.affiliation: Nemucore Medical Innovations, Inc. ; Worcester, MA USA.
authors.forename: Eileen
authors.initials: E
authors.lastname: Wrabel
authors.affiliation: Nemucore Medical Innovations, Inc. ; Worcester, MA USA.
authors.forename: Mary E
authors.initials: ME
authors.lastname: Schwartz
authors.affiliation: Blue Ocean Biomanufacturing , Worcester, MA USA ; Nemucore Medical Innovations, Inc. ; Worcester, MA USA ; Center for Translational Cancer Nanomedicine; Northeastern University ; Boston, MA USA ; Foundation for the Advancement of Personalized Medicine Manufacturing ; Phoenix, AZ USA.
authors.forename: Timothy P
authors.initials: TP
authors.lastname: Coleman
authors.affiliation: Barrow Brain Tumor Research Center; Barrow Neurological Institute ; Phoenix, AZ USA.
authors.forename: Rachael W
authors.initials: RW
authors.lastname: Sirianni
keywords: DGL, dendrigraft poly-l-lysine; Drug delivery; GABA, gamma-aminobutyric acid receptor; MMP-2, matrix metalloprotease-2; NCAM, neural cell adhesion molecule; NMDA, N-methyl-D-aspartate; PEG, polyethylene glycol; PEI, polyethylenimine; brain; central nervous system; nAchR, nicotinic acetylcholine receptor; pathogen; peptide; toxin