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
| Autor: | Mariana Rodrigues Pereira, José Mauro Granjeiro, Helena T. Hogberg, David Pamies, Thomas Hartung, Georgina Harris, Lisia Maria Gobbo dos Santos, Lena Smirnova, Paulo Emílio Corrêa Leite |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Health
Toxicology and Mutagenesis Cell Culture Techniques Gene Expression Metal Nanoparticles Toxicology Polyethylene Glycols Nanoparticle Drug Delivery Systems Membrane Potential Mitochondrial 0303 health sciences Nanoparticle Drug delivery CNS iPSC-derived BrainSpheres 3D LUHMES Chemistry Neurodegeneration Brain General Medicine Human brain 3D LUHMES CNS Drug delivery iPSC-derived BrainSpheres Cell biology medicine.anatomical_structure Cell Survival Surface Properties Polyesters lcsh:Industrial hygiene. Industrial welfare Blood–brain barrier Sodium Citrate Models Biological Cell Line 03 medical and health sciences lcsh:RA1190-1270 In vivo ddc:570 Spheroids Cellular medicine Humans Neuroinflammation lcsh:Toxicology. Poisons Research Dopaminergic Neurons Neurotoxicity 030311 toxicology medicine.disease In vitro Oxidative Stress Gold lcsh:HD7260-7780.8 |
| Zdroj: | Particle and fibre toxicology, vol. 16, no. 1, pp. 22 Particle and Fibre Toxicology Particle and Fibre Toxicology, Vol 16, Iss 1, Pp 1-20 (2019) |
| Popis: | Background The blood brain barrier (BBB) is the bottleneck of brain-targeted drug development. Due to their physico-chemical properties, nanoparticles (NP) can cross the BBB and accumulate in different areas of the central nervous system (CNS), thus are potential tools to carry drugs and treat brain disorders. In vitro systems and animal models have demonstrated that some NP types promote neurotoxic effects such as neuroinflammation and neurodegeneration in the CNS. Thus, risk assessment of the NP is required, but current 2D cell cultures fail to mimic complex in vivo cellular interactions, while animal models do not necessarily reflect human effects due to physiological and species differences. Results We evaluated the suitability of in vitro models that mimic the human CNS physiology, studying the effects of metallic gold NP (AuNP) functionalized with sodium citrate (Au-SC), or polyethylene glycol (Au-PEG), and polymeric polylactic acid NP (PLA-NP). Two different 3D neural models were used (i) human dopaminergic neurons differentiated from the LUHMES cell line (3D LUHMES) and (ii) human iPSC-derived brain spheroids (BrainSpheres). We evaluated NP uptake, mitochondrial membrane potential, viability, morphology, secretion of cytokines, chemokines and growth factors, and expression of genes related to ROS regulation after 24 and 72 h exposures. NP were efficiently taken up by spheroids, especially when PEGylated and in presence of glia. AuNP, especially PEGylated AuNP, effected mitochondria and anti-oxidative defense. PLA-NP were slightly cytotoxic to 3D LUHMES with no effects to BrainSpheres. Conclusions 3D brain models, both monocellular and multicellular are useful in studying NP neurotoxicity and can help identify how specific cell types of CNS are affected by NP. Electronic supplementary material The online version of this article (10.1186/s12989-019-0307-3) contains supplementary material, which is available to authorized users. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|