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A Stoichiometrically Defined Neural Coculture Model to Screen Nanoparticles for Neurological Applications

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Use of Nanoparticles in Neuroscience

Part of the book series: Neuromethods ((NM,volume 135))

Abstract

In neuronanotherapeutics, regenerative goals could be achieved by designing therapeutic nanoparticles to target, or evade, specific neural cell types. However, effective screening of candidate particles is hampered by the limited neuromimetic capacity of available biological models. Central nervous system (CNS) tissue is composed of multiple specialized cell types, with dramatically differing particle uptake profiles, dominated by microglia, the ubiquitous immune component of the CNS, resulting in competition for particle uptake. Such dynamics are difficult to monitor in vivo, while in vitro monocultures lack competitive uptake and so predictive value. Available coculture systems are frequently oversimplistic, lack reproducible composition and/or fail to include the immune component. Further, cell-specific culture media are often employed for each neural cell type, leading to differences in protein corona formation around particles, potentially confounding cross-cellular analyses. We describe a novel coculture system that can overcome these limitations, and discuss its utility for assessing uptake, toxicity, and functional efficacy of nanoparticles intended for neurological applications.

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Acknowledgments

We thank the following for advice on protocol development, equipment operation and analysis techniques: Chris Adams, James Beardmore, Alinda Fernandes, David Furness, Mark Pickard, Paul Roach, Emma Shardlow, Jacqueline Tickle, Karen Walker, Alan Weightman (all Keele University), and Humphrey Yiu (Heriot-Watt University). These protocols were developed while SJ was supported by an Engineering and Physical Sciences Research Council (EPSRC; UK) Engineering Tissue Engineering and Regenerative Medicine (E-TERM) Landscape Fellowship (EP/I017801/1).

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Authors and Affiliations

  1. School of Medicine, Institute for Science and Technology in Medicine, Keele University, Keele, Newcastle, ST5 5BG, UK

    Stuart I. Jenkins & Divya M. Chari

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  1. Stuart I. Jenkins
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  2. Divya M. Chari
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Correspondence to Stuart I. Jenkins .

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Editors and Affiliations

  1. Department of Biology, The University of Texas at San Antonio, San Antonio, Texas, USA

    Fidel Santamaria

  2. Air Force Research Laboratory, 711 HPW/RHDR, Fort Sam Houston, Texas, USA

    Xomalin G. Peralta

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Jenkins, S.I., Chari, D.M. (2018). A Stoichiometrically Defined Neural Coculture Model to Screen Nanoparticles for Neurological Applications. In: Santamaria, F., Peralta, X. (eds) Use of Nanoparticles in Neuroscience. Neuromethods, vol 135. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-7584-6_14

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  • DOI: https://doi.org/10.1007/978-1-4939-7584-6_14

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  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-7582-2

  • Online ISBN: 978-1-4939-7584-6

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