TY - JOUR
T1 - Heterocellular spheroids of the neurovascular blood-brain barrier as a platform for personalized nanoneuromedicine
AU - Kumarasamy, Murali
AU - Sosnik, Alejandro
N1 - Publisher Copyright:
© 2021 The Author(s)
PY - 2021/3/19
Y1 - 2021/3/19
N2 - 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 upregulate 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 (NPs). Findings reveal that penetration and distribution patterns depend on the NP 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, nanosafety and nanotoxicology.
AB - 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 upregulate 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 (NPs). Findings reveal that penetration and distribution patterns depend on the NP 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, nanosafety and nanotoxicology.
KW - Biomaterials
KW - Cellular Neuroscience
KW - Experimental Models in Systems Biology
KW - Nanotechnology
UR - http://www.scopus.com/inward/record.url?scp=85101497128&partnerID=8YFLogxK
U2 - 10.1016/j.isci.2021.102183
DO - 10.1016/j.isci.2021.102183
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AN - SCOPUS:85101497128
VL - 24
JO - iScience
JF - iScience
IS - 3
M1 - 102183
ER -