Imaging approach to mechanistic study of nanoparticle interactions with the blood–brain barrier Bramini, Mattia Ye, Dong Hallerbach, Anna Nic Raghnaill, Michelle Salvati, Anna Åberg, Christoffer Dawson, Kenneth A. Blood−brain barrier Nanoparticles Transcytosis Funding for this project has been generously provided by EU FP7 via the small collaborative project NeuroNano (NNP4-SL-2008-214547) and the small collaborative project NanoTransKinetics (NMP4-2010-EU-US-266737); by the INSPIRE (Integrated NanoScience Platform for IREland) program funded by the Irish Government’s Programme for Research in Third Level Institutions, Cycle 4, National Development Plan 2007-2013; and by Science Foundation Ireland (09/RFP/MTR2425). Additionally it is based upon works supported by Science Foundation Ireland (SFI/SRC/B1155 and 12/IA/1422), EU FP7, via the Marie-Curie Initial Training Network PathChooser (PITN-GA-2013-608373) and the ESF Research Networking Programme EpitopeMap. Understanding nanoparticle interactions with the central nervous system, in particular the blood–brain barrier, is key to advances in therapeutics, as well as assessing the safety of nanoparticles. Challenges in achieving insights have been significant, even for relatively simple models. Here we use a combination of live cell imaging and computational analysis to directly study nanoparticle translocation across a human in vitro blood–brain barrier model. This approach allows us to identify and avoid problems in more conventional inferential in vitro measurements by identifying the catalogue of events of barrier internalization and translocation as they occur. Potentially this approach opens up the window of applicability of in vitro models, thereby enabling in depth mechanistic studies in the future. Model nanoparticles are used to illustrate the method. For those, we find that translocation, though rare, appears to take place. On the other hand, barrier uptake is efficient, and since barrier export is small, there is significant accumulation within the barrier. 2026-02-17T11:03:32Z 2026-02-17T11:03:32Z 2014-04-28 journal article Bramini, Mattia et al. Imaging approach to mechanistic study of nanoparticle interactions with the blood–brain barrier. 2014, ACS nano 8 (5), 4304-4312. DOI: 10.1021/nn5018523 https://hdl.handle.net/10481/111087 10.1021/nn5018523 eng info:eu-repo/grantAgreement/EC/FP7/NNP4-SL-2008-214547 info:eu-repo/grantAgreement/EC/FP7/NMP4-2010-EU-US-266737 http://creativecommons.org/licenses/by-nc-nd/4.0/ open access Attribution-NonCommercial-NoDerivatives 4.0 Internacional American Chemical Society