Heterocellular Spheroids of the Neurovascular Blood-Brain Barrier as A Platform for Personalized Nanoneuromedicine

Summary Nanoneuromedicine investigates nanotechnology to target the brain and treat neurological diseases. In this work, we biofabricated heterocellular spheroids comprising human brain microvascular endothelial cells, brain vascular pericytes and astrocytes combined with primary cortical neurons and microglia isolated from neonate rats. The structure and function are characterized by confocal laser scanning and light sheet fluorescence microscopy, electron microscopy, western blotting, and RNA-sequencing. The spheroid bulk is formed by neural cells and microglia and the surface by endothelial cells and they up-regulate key structural and functional proteins of the blood-brain barrier. These cellular constructs are utilized to preliminary screen the permeability of polymeric, metallic, and ceramic nanoparticles. Findings reveal that penetration and distribution patterns depend on the nanoparticle type and that microglia would play a key role in this pathway, highlighting the promise of this platform to investigate the interaction of different nanomaterials with the central nervous system in nanomedicine and nanotoxicology.