Development of a nanomaterial bio-screening platform for neurological applications

Jenkins, SI; Roach, P; Chari, DM

Abstract

Nanoparticle platforms are being intensively investigated for neurological applications. Current biological models used to identify clinically relevant materials have major limitations, e.g. technical/ethical issues with live animal experimentation, failure to replicate neural cell diversity, limited control over cellular stoichiometries and poor reproducibility. High-throughput neuro-mimetic screening systems are required to address these challenges. We describe an advanced multicellular neural model comprising the major non-neuronal/glial cells of the central nervous system (CNS), shown to account for ~99.5% of CNS nanoparticle uptake. This model offers critical advantages for neuro-nanomaterials testing while reducing animal use: one primary source and culture medium for all cell types, standardized biomolecular corona formation and defined/reproducible cellular stoichiometry. Using dynamic time-lapse imaging, we demonstrate in real-time that microglia (neural immune cells) dramatically limit particle uptake in other neural subtypes (paralleling post-mortem observations after nanoparticle injection in vivo), highlighting the utility of the system in predicting neural handling of biomaterials.

Citation

Jenkins, S., Roach, P., & Chari, D. (2015). Development of a nanomaterial bio-screening platform for neurological applications. Nanomedicine: Nanotechnology, Biology and Medicine, 77 - 87. https://doi.org/10.1016/j.nano.2014.07.010

• Acceptance Date: Jul 22, 2014
• Publication Date: Jan 1, 2015
• Journal: Nanomedicine: Nanotechnology, Biology and Medicine
• Print ISSN: 1549-9634
• Publisher: Elsevier
• Pages: 77 - 87
• DOI: https://doi.org/10.1016/j.nano.2014.07.010
• Keywords: biomaterials screening, glia, multicellular models, neural cells, protein corona, animal use alternatives, animals, astrocytes, biocompatible materials, central nervous system, coculture techniques, culture media, croglia, microscopy, fluorescence, nanome
• Publisher URL: http://dx.doi.org/10.1016/j.nano.2014.07.010