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Antiangiogenic Effect of Graphene Oxide in Primary Human Endothelial Cells
Giulia Cibecchini1,2, Marina Veronesi3, Tiziano Catelani4,5
1Nanobiointeractions&Nanodiagnostics, Istituto Italiano di Tecnologia (IIT), Via Morego 30, 16163 Genova, Italy.
Abstract:
In this work, we exploited an integrated approach combining systematic analysis of cytotoxicity, angiogenic potential, and metabolomics to shed light on the effects of graphene oxide (GO) on primary human endothelial Huvec cells. Contrary to the outcomes observed in immortalized cell lines able to internalize a similar amount of GO, significant toxicity was found in Huvec cells at high GO concentrations (25 and 50 μg/mL). In particular, we found that the steric hindrance of GO intracellular aggregates perturbed the correct assembly of cytoskeleton and distribution of mitochondria. This was found to be primarily associated with oxidative stress and impairment of cell migration, affecting the formation of capillary-like structures. In addition, preliminary metabolomics characterization demonstrated that GO affects the consumption of niacinamide, a precursor of energy carriers, and several amino acids involved in the regulation of angiogenesis. Our findings suggest that GO acts at different cellular levels, both directly and indirectly. More precisely, the combination of the physical hindrance of internalized GO aggregates, induction of oxidative stress, and alteration of some metabolic pathways leads to a significant antiangiogenic effect in primary human endothelial cells.
Insights
Graphene oxide (GO) causes toxicity and anti-angiogenic effects in primary human endothelial cells by disrupting cell structure and metabolism. This contrasts with findings in immortalized cell lines.
Area of Science:
- Biomaterials Science
- Cell Biology
- Toxicology
Background:
- Graphene oxide (GO) is a nanomaterial with potential biomedical applications.
- Its effects on primary human endothelial cells, crucial for blood vessel formation, require detailed investigation.
- Previous studies on immortalized cell lines may not fully represent GO's impact on primary cells.
Purpose of the Study:
- To investigate the cytotoxicity and anti-angiogenic effects of graphene oxide (GO) on primary human endothelial cells (Huvec).
- To elucidate the cellular and metabolic mechanisms underlying GO's impact.
- To compare GO's effects on primary cells versus immortalized cell lines.
Main Methods:
- Systematic analysis of cytotoxicity using primary human endothelial Huvec cells.
- Assessment of angiogenic potential, including cell migration and capillary-like structure formation.
- Metabolomics profiling to identify affected metabolic pathways.
- Microscopic analysis of cytoskeleton and mitochondria distribution.
Main Results:
- Significant toxicity of GO observed in Huvec cells at high concentrations (25 and 50 μg/mL).
- Intracellular GO aggregates caused steric hindrance, disrupting cytoskeleton and mitochondria.
- GO induced oxidative stress, impaired cell migration, and inhibited capillary-like structure formation.
- Metabolomics revealed altered consumption of niacinamide and amino acids involved in angiogenesis.
Conclusions:
- Graphene oxide exhibits significant anti-angiogenic effects on primary human endothelial cells.
- Mechanisms include physical hindrance by aggregates, oxidative stress, and metabolic pathway alterations.
- Findings highlight differential responses between primary and immortalized endothelial cells to GO exposure.
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