Imaging approach to mechanistic study of nanoparticle interactions with the blood-brain barrier.
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.
Centre for BioNano Interactions, School of Chemistry and Chemical Biology & UCD Conway Institute for Biomolecular and Biomedical Research, University College Dublin , Belfield, Dublin 4, Ireland.
Mattia
M
Bramini
Dong
D
Ye
Anna
A
Hallerbach
Michelle
M
Nic Raghnaill
Anna
A
Salvati
Christoffer
C
Aberg
Kenneth A
KA
Dawson
D001812:Blood-Brain Barrier; D001921:Brain / Q000098:blood supply; D002196:Capillaries / Q000473:pathology; D002460:Cell Line; D003094:Collagen / Q000737:chemistry; D003198:Computer Simulation; D003470:Culture Media / Q000737:chemistry; D004337:Drug Carriers; D006801:Humans; D008247:Lysosomes / Q000737:chemistry; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D053758:Nanoparticles / Q000737:chemistry*; D036103:Nanotechnology / Q000379:methods*; D013696:Temperature; D057900:Transcytosis
D003470:Culture Media; D004337:Drug Carriers; D003094:Collagen