3D-Brainspheres as model for nanoparticle-associated substances
2019
Center for Alternatives to Animal Testing (CAAT), Johns Hopkins Bloomberg School of Public Health, Baltimore, USA
Nanoparticles (NP) can cross the blood-brain-barrier (BBB) and accumulate in different areas of the central nervous system (CNS), thus are potential tools to carry drugs and treat brain disorders. The effects of different NP were studied in human LUHMES cell line (3D LUHMES) and human iPSC-derived brain spheroids (BrainSpheres). The simpler, single-cell model was more sensitive to the toxic effects, in line with the lack of glia support to neurons. In BrainSpheres the NP, especially modified with specific ligands, can cross the BBB and show higher levels due to the presence of glial cells whose function is to facilitate uptake. Nevertheless, decrease of viability or morphological alterations was not observed, maybe due to activation of cell survival programs.
Therefore, 3D brain spheroid models incorporating microglia are well suited to comparatively characterize NP neurotoxicity. The use of multiple models, which encompass simplicity and physiological relevance, serves as a tool for more NP drug-delivery focused research.
Suitability of 3D human brain spheroid models to distinguish toxic effects of gold and poly-lactic acid nanoparticles to assess biocompatibility for brain drug delivery
Lena Smirnova
Added on: 08-28-2020
[1] https://particleandfibretoxicology.biomedcentral.com/articles/10.1186/s12989-019-0307-3
