Evidence map›Paper›PMID 31159811›Full record

ArticleParticle and fibre toxicology2019

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.

Paulo Emílio Corrêa Leite, Mariana Rodrigues Pereira, Georgina Harris, David Pamies, Lisia Maria Gobbo Dos Santos, José Mauro Granjeiro, Helena T Hogberg, Thomas Hartung, Lena Smirnova

Open access · goldAbstract read
In one paragraph

Article in Particle and fibre toxicology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
48citing papers in PubMed, 1 pooled it
4.3field-weighted citation impact, top 5% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

48 citing papers in PubMed, 1 synthesis or guideline pooled it, 86 citations in OpenAlex.

  1. Pooled it
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  4. Beyond monolayers: a comparative analysis of 2D cell cultures and 3DFrontiers in bioengineering and biotechnology · 2026
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  20. Advances in currentFrontiers in bioengineering and biotechnology · 2023
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 4 institutions in 5 countries.

Paulo Emílio Corrêa LeiteDirectory of Metrology Applied to Life Sciences - Dimav, National Institute of Metrology Quality and Technology - INMETRO, Av. Nossa Senhora das Graças 50, LABET - Dimav, Predio 27, Duque de Caxias, Xerem, Rio de Janeiro, 25250-020, Brazil. leitepec@gmail.com.
Mariana Rodrigues PereiraBiology Institute, Fluminense Federal University, Niteroi, Rio de Janeiro, Brazil.
Georgina HarrisCenter for Alternatives to Animal Testing (CAAT), Bloomberg School of Public Health, Johns Hopkins University, 615 N. Wolfe Street, Baltimore, MD, 21205, USA.
David PamiesCenter for Alternatives to Animal Testing (CAAT), Bloomberg School of Public Health, Johns Hopkins University, 615 N. Wolfe Street, Baltimore, MD, 21205, USA.
Lisia Maria Gobbo Dos SantosDepartment of Chemistry, National Institute of Quality Control in Health - INCQS/Fiocruz, Manguinhos, Rio de Janeiro, 21040-900, Brazil.
José Mauro GranjeiroDirectory of Metrology Applied to Life Sciences - Dimav, National Institute of Metrology Quality and Technology - INMETRO, Av. Nossa Senhora das Graças 50, LABET - Dimav, Predio 27, Duque de Caxias, Xerem, Rio de Janeiro, 25250-020, Brazil.
Helena T HogbergCenter for Alternatives to Animal Testing (CAAT), Bloomberg School of Public Health, Johns Hopkins University, 615 N. Wolfe Street, Baltimore, MD, 21205, USA.
Thomas HartungCenter for Alternatives to Animal Testing (CAAT), Bloomberg School of Public Health, Johns Hopkins University, 615 N. Wolfe Street, Baltimore, MD, 21205, USA.
Lena SmirnovaCenter for Alternatives to Animal Testing (CAAT), Bloomberg School of Public Health, Johns Hopkins University, 615 N. Wolfe Street, Baltimore, MD, 21205, USA. lsmirno1@jhu.edu.ORCID 0000-0003-0171-3881
Johns Hopkins University · USUniversidade Federal Fluminense · BRInstituto Nacional de Metrologia, Qualidade e Tecnologia · BRNational Council for Scientific and Technological Development · BR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe 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.

resultsWe 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.

conclusions3D 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.

Indexed as

Models, BiologicalBrainCell Culture TechniquesCell LineCell SurvivalDopaminergic NeuronsDrug Delivery SystemsGene ExpressionGoldHumansMembrane Potential, MitochondrialMetal NanoparticlesOxidative StressPolyestersPolyethylene GlycolsSodium CitrateGoldPolyestersPolyethylene Glycolspoly(lactide)Sodium Citrate3D LUHMESCNSDrug deliveryiPSC-derived BrainSpheresNanoparticle

Identifiers

PMID31159811
PMCPMC6545685
OpenAlexW2949003121

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.