title: Internal benchmarking of a human blood-brain barrier cell model for screening of nanoparticle uptake and transcytosis.
abstract: Transport of drugs across the blood-brain barrier, which protects the brain from harmful agents, is considered the holy grail of targeted delivery, due to the extreme effectiveness of this barrier at preventing passage of non-essential molecules through to the brain. This has caused severe limitations for therapeutics for many brain-associated diseases, such as HIV and neurodegenerative diseases. Nanomaterials, as a result of their small size (in the order of many protein-lipid clusters routinely transported by cells) and their large surface area (which acts as a scaffold for proteins thereby rendering nanoparticles as biological entities) offer great promise for neuro-therapeutics. However, in parallel with developing neuro-therapeutic applications based on nanotechnology, it is essential to ensure their safety and long-term consequences upon reaching the brain. One approach to determining safe application of nanomaterials in biology is to obtain a deep mechanistic understanding of the interactions between nanomaterials and living systems (bionanointeractions). To this end, we report here on the establishment and internal round robin validation of a human cell model of the blood-brain barrier for use as a tool for screening nanoparticles interactions, and assessing the critical nanoscale parameters that determine transcytosis.
authors.affiliation: School of Chemistry & Chemical Biology, and UCD Conway Institute, University College Dublin, Dublin, Ireland. michelle.nicraghnaill@ucd.ie
authors.forename: Michelle Nic
authors.initials: MN
authors.lastname: Ragnaill
authors.forename: Meredith
authors.initials: M
authors.lastname: Brown
authors.forename: Dong
authors.initials: D
authors.lastname: Ye
authors.forename: Mattia
authors.initials: M
authors.lastname: Bramini
authors.forename: Sean
authors.initials: S
authors.lastname: Callanan
authors.forename: Iseult
authors.initials: I
authors.lastname: Lynch
authors.forename: Kenneth A
authors.initials: KA
authors.lastname: Dawson
mesh_terms: D019985:Benchmarking; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D018929:Cell Culture Techniques; D002460:Cell Line; D004337:Drug Carriers / Q000008:administration & dosage* / Q000737:chemistry / Q000633:toxicity; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D005260:Female; D006801:Humans; D046529:Microscopy, Electron, Transmission; D008954:Models, Biological; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry / Q000633:toxicity; D010539:Permeability; D004364:Pharmaceutical Preparations / Q000008:administration & dosage / Q000378:metabolism*; D015203:Reproducibility of Results; D057900:Transcytosis / Q000187:drug effects*
chemical_list: D004337:Drug Carriers; D004364:Pharmaceutical Preparations