title: Paracrine signalling of inflammatory cytokines from an in vitro blood brain barrier model upon exposure to polymeric nanoparticles.
abstract: Nanoparticle properties, such as small size relative to large highly modifiable surface area, offer great promise for neuro-therapeutics and nanodiagnostics. A fundamental understanding and control of how nanoparticles interact with the blood-brain barrier (BBB) could enable major developments in nanomedical treatment of previously intractable neurological disorders, and help ensure that nanoparticles not intended to reach the brain do not cause adverse effects. Nanosafety is of utmost importance to this field. However, a distinct lack of knowledge exists regarding nanoparticle accumulation within the BBB and the biological effects this may induce on neighbouring cells of the Central Nervous System (CNS), particularly in the long-term. This study focussed on the exposure of an in vitro BBB model to model carboxylated polystyrene nanoparticles (PS COOH NPs), as these nanoparticles are well characterised for in vitro experimentation and have been reported as non-toxic in many biological settings. TEM imaging showed accumulation but not degradation of 100 nm PS COOH NPs within the lysosomes of the in vitro BBB over time. Cytokine secretion analysis from the in vitro BBB post 24 h 100 nm PS COOH NP exposure showed a low level of pro-inflammatory RANTES protein secretion compared to control. In contrast, 24 h exposure of the in vitro BBB endothelium to 100 nm PS COOH NPs in the presence of underlying astrocytes caused a significant increase in pro-survival signalling. In conclusion, the tantalising possibilities of nanomedicine must be balanced by cautious studies into the possible long-term toxicity caused by accumulation of known 'toxic' and 'non-toxic' nanoparticles, as general toxicity assays may be disguising significant signalling regulation during long-term accumulation.
authors.affiliation: Centre for BioNano Interactions, School of Chemistry and Chemical Biology, University College Dublin, Belfield, Dublin 4, Ireland. kenneth.a.dawson@cbni.ucd.ie.
authors.forename: Michelle Nic
authors.initials: MN
authors.lastname: Raghnaill
authors.forename: Mattia
authors.initials: M
authors.lastname: Bramini
authors.forename: Dong
authors.initials: D
authors.lastname: Ye
authors.forename: Pierre-Olivier
authors.initials: PO
authors.lastname: Couraud
authors.forename: Ignacio A
authors.initials: IA
authors.lastname: Romero
authors.forename: Babette
authors.initials: B
authors.lastname: Weksler
authors.forename: Christoffer
authors.initials: C
authors.lastname: Åberg
authors.forename: Anna
authors.initials: A
authors.lastname: Salvati
authors.forename: Iseult
authors.initials: I
authors.lastname: Lynch
authors.forename: Kenneth A
authors.initials: KA
authors.lastname: Dawson
mesh_terms: D001812:Blood-Brain Barrier / Q000187:drug effects / Q000378:metabolism*; D002461:Cell Line, Transformed; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D016207:Cytokines / Q000378:metabolism*; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D053758:Nanoparticles / Q000633:toxicity*; D019899:Paracrine Communication / Q000187:drug effects / Q000502:physiology*; D011108:Polymers / Q000633:toxicity*
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D011108:Polymers