Antiangiogenic Effect of Graphene Oxide in Primary Human Endothelial Cells

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.

Efficacy of graphene oxide-loaded cationic antimicrobial peptide AWRK6 on the neutralization of endotoxin activity and in the treatment of sepsis

“…GO nanoplatelets improve anti-cancer effect of cisplatin on human lung cancer cells [24]. It has been found GO induces anti-angiogenic impact of GO in primary human endothelial cells [25].…”

Advances in Biologically Applicable Graphene-Based 2D Nanomaterials

“…A considerable antiangiogenic effect of GO in primary human endothelial Huvec cells was due to the combination of the physical hindrance of internalized GO aggregates, induction of oxidative stress, and alteration of some metabolic pathways. Besides, steric hindrance of GO intracellular aggregates, perturbing the correct assembly of cytoskeleton and distribution of mitochondria and causing impairment of cell migration, affected the formation of capillary-like structures and the consumption of niacinamide, which is a precursor of energy carriers, as well as several amino acids involved in the regulation of angiogenesis [ 128 ].…”

<p>Applications of Graphene and Graphene Oxide in Smart Drug/Gene Delivery: Is the World Still Flat?</p>

“…182 Similarly, in a more recent study, GO showed an anti-angiogenesis effect on HUVECs through the induction of oxidative stress and the manipulation of some metabolic pathways. 183 Focusing on the strong correlation between the level of ROS and NF-κB activation, the NF-κB related anti-angiogenesis effect of graphite nanoparticles and graphene oxide nanoplatelets (nGO) was assessed on both p53 mutant and wild type of glioblastoma cancer cells. The treatment of HUVECs co-cultured with p53 wild type of glioblastoma (U87) attenuated their strength for angiogenesis but not for p53 mutant group (U118).…”