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, nanomedicine, nanoparticles, nanostructures, neuroglia, neurons, oligodendroglia, reproducibility of results, spectroscopy, fourier transform infrared
• Publisher URL: http://dx.doi.org/10.1016/j.nano.2014.07.010