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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.

The search for understanding the interactions of nanosized materials with living organisms is leading to the rapid development of key applications, including improved drug delivery by targeting nanoparticles, and resolution of the potential threat of nanotechnological devices to organisms and the environment. Unless they are specifically designed to avoid it, nanoparticles in contact with biological fluids are rapidly covered by a selected group of biomolecules to form a corona that interacts with biological systems. Here we review the basic concept of the nanoparticle corona and its structure and composition, and highlight how the properties of the corona may be linked to its biological impacts. We conclude with a critical assessment of the key problems that need to be resolved in the near future.

Central to understanding how nanoscale objects interact with living matter is the need for reproducible and verifiable data that can be interpreted with confidence. Likely this will be the basis of durable advances in nanomedicine and nanomedical safety. To develop these fields, there is also considerable interest in advancing the first generation of theoretical models of nanoparticle (NP) uptake into cells, and NP biodistribution in general. Here we present an uptake study comparing the outcomes for free molecular dye and NPs labeled with the same dye. A simple flux-based approach is presented to model NP uptake. We find that the intracellular NP concentration grows linearly in time, and that the uptake is essentially irreversible, with the particles accumulating in lysosomes. A wide range of practical challenges, from labile dye release to NP aggregation and the need to account for cell division, are addressed to ensure that these studies yield meaningful kinetic information., From the Clinical Editor: The authors present an uptake study comparing the outcomes for free molecular dye and NPs labeled with the same dye. A wide range of practical challenges are addressed including labile dye release, NP aggregation and the need to account for cell division with the goal that these studies yield meaningful kinetic information., (Copyright © 2011 Elsevier Inc. All rights reserved.)