Development of a nanomaterial bio-screening platform for neurological applications

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.From the Clinical EditorThe authors describe an advanced multicellular neural model comprising the major non-neuronal/glial cells of the central nervous system, shown to account for approximately 99.5% of CNS nanoparticle uptake. They demonstrate that this novel model offers critical advantages for neuro-nanomaterials testing, while reducing the need for experimental animals.

Graphical AbstractA novel neural cell co-culture model developed in this work has been used to control cellular stoichiometry and standardize bimolecular corona formation around magnetic particles (MPs). The model has been employed to demonstrate in real-time, for the first time, that rapid and extensive MP accumulation by microglial cells dramatically limits uptake by other major neural cell types such as astrocytes and oligodendrocyte precursor cells, representing a major extracellular barrier to particle uptake. These findings parallel in vivo observations post-nanoparticle injection, highlighting the predictive utility and material screening capacity of the model.Figure optionsDownload high-quality image (197 K)Download as PowerPoint slide