Paracrine signalling of inflammatory cytokines from an in vitro blood brain barrier model upon exposure to polymeric nanoparticles Nic Raghnaill, Michelle Bramini, Mattia Ye, Dong Couraud, Pierre-Olivier Romero, Ignacio A Weksler, Babette Aberg, Christoffer Salvati, Anna Lynch, Iseult Dawson, Kenneth A Nanoparticles Cytokines Blood−brain barrier This research has been supported by the EU FP7 Small Collaborative project NeuroNano, NMP4-SL-2008-214547 (M.N.R., M.B., I.L.), and by a UCD SEED grant (SF224). Part of this work was conducted under the framework of the INSPIRE programme, funded by the Irish Government’s Programme for Research in Third Level Institutions, Cycle 4, National Development Plan 2007-2013 (D.Y., A.S.), as well as Science Foundation Ireland under Grant no. [09/RFP/MTR2425] (C.A.) and EU ˚ FP7 via the small collaborative project NanoTransKinetics (grant no. NMP4-2010-EU-US-266737) (C.A.). Use of the UCD ˚ Conway Imaging Facility and the UCD Electron Microscopy Core facility is also acknowledged. 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. 2026-02-17T09:24:10Z 2026-02-17T09:24:10Z 2013-10-16 journal article Nic Raghnaill, M.; Bramini, M.; Ye, D. [et al]. (2013). Paracrine signalling of inflammatory cytokines from an in vitro blood brain barrier model upon exposure to polymeric nanoparticles. Analyst, volume 139 (5), 923-930. DOI: 10.1039/c3an01621h 1364-5528 https://hdl.handle.net/10481/111061 10.1039/C3AN01621H eng http://creativecommons.org/licenses/by-nc-nd/4.0/ open access Attribution-NonCommercial-NoDerivatives 4.0 Internacional Royal Society of Chemistry