<p>Comparative study of in vitro effects of different nanoparticles at non-cytotoxic concentration on the adherens junction of human vascular endothelial cells</p>

Abstract

Background Effects of different nanoparticles (NPs) exposure at acutely non-cytotoxic concentrations are particularly worthy to figure out, compare, and elucidate. Objective To investigate and compare the effect of a small library of NPs at non-cytotoxic concentration on the adherens junction of human umbilical vein endothelial cells (HUVECs), obtaining new insights of NPs safety evaluation. Materials and methods The HUVECs layer was exposed to NPs including gold (Au), platinum (Pt), silica (SiO 2 ), titanium dioxide (TiO 2 ), ferric oxide (Fe 2 O 3 ), oxidized multi-walled carbon nanotubes, with different surface chemistry and size distribution. Cellular uptake of NPs was observed by transmission electron microscopy. and the cytotoxicity was determined by Cell Counting Kit-8 assay. The NP-induced variation of intracellular reactive oxygen species (ROS) and catalase (CAT) activity was measured using the probe of 2ʹ7’-dichlorodihydr fluorescein diacetate and a CAT analysis kit, respectively. The level of VE-cadherin of HUVECs was analyzed by Western blot, and the loss of adherens junction was observed with laser confocal microscopy. Results The acutely non-cytotoxic concentrations of different NPs were determined and applied to HUVECs. The NPs increased the level of intracellular ROS and the activity of CAT to different degrees, depending on the characteristics. At the same time, the HUVECs lost their adherens junction protein VE-cadherin and gaps were formed between the cells. The NP-induced oxidative stress and gap formation could be rescued by the supplementary N-acetylcysteine in the incubation. Conclusion The increase of intracellular ROS and CAT activity was one common effect of NPs, even at the non-cytotoxic concentration, and the degree was dependent on the composition, surface chemistry, and size distribution of the NP. The effect led to the gap formation between the cells, while could be rescued by the antioxidant. Therefore, the variation of adherens junction between endothelial cells was suggested to evaluate for NPs when used as therapeutics and diagnostics.

Gold Nanoparticles Functionalized with Angiogenin for Wound Care Application

“…; Au, Pt, Ag), coating and size. In agreements with literature data which demonstrate that citrate capped AuNPs with a size between 10 and 50 nm do not affect the viability of HUVECs in a concentration range 0.1–100 nM [ 91 , 92 ], our results did not evidence cytotoxic effect at the tested conditions. Similarly, the hybrids both in the absence and in the presence of copper did not show any cytotoxicity evidencing the good potentialities of our protein-conjugated NPs as cell specific, angiogenic nanomedicine tools.…”

The Interactions of Quantum Dot-Labeled Silk Fibroin Micro/Nanoparticles with Cells

“…At a low concentration of SFNPs (0.05 mg/mL), the EA.hy926 cell proliferation was significantly inhibited. The results were similar to the previous studies where the nanoparticles with concentration of <240 μg/mL were significantly cytotoxic for vascular endothelial cells [ 53 ]. Interestingly, though the normal cell proliferation was significantly inhibited when the concentration of SFNPs < 0.5 mg/mL, there is tendency that the cell viability is increased.…”

Organ-on-a-chip platforms for evaluation of environmental nanoparticle toxicity

“… [ 113 ] Various nanoparticles HUVEC Exposure to nanoparticles increase the level of intracellular ROS and activate catalase, which disrupt VE-cadherin adherents junction. [ 16 ] Heart Injury 38 nm TiO 2 nanoparticles Rats Intratracheal Instillation Exposure to nanoparticles leads to irreversible cardiac function and structural remodeling of hypertensive heart. [ 65 ] 62 nm SiO 2 nanoparticles Zebrafish Induces pericardial edema and bradycardia through inhibition of calcium signaling pathway and cardiac muscle contraction pathway via the downregulation of proteins related to ATPase, calcium channel, and cardiac troponin C. [ 114 ] 7- and 670 nm SiO 2 nanoparticles Isolated rat cardiomyocytes Nanoparticles interfere with cardiac function through impairment of Ca 2+ handling and reduction in cell shortening which is caused by mitochondrial malfunction.…”

“…While these scientific data, been generated from conventional systems are relatively robust, reproducible, easy to analyze, and more suitable for high-throughput toxicity screening given the vast variations in nanoparticle size, charge, shape, and composition, it is questionable if those methods can provide insightful interpretation to regulators on the potential nano-toxic effects on human tissues and organs. Unlike our native human organs, traditional 2D cell culture methods still lack the complex three-dimensional (3D) cell-cell and cell-matrix interactions, and they are restricted to the use of immortalized human cell lines that do not exhibit phenotypes similar to the human primary cells [ 16 , 17 ], resulting in inaccuracy and discrepancy in the prediction of toxicity. Although animal models are useful in predicting nanoparticle toxicity at the systemic level, it is notably challenging to extract the precise molecular mechanisms due to the discrepancy in physiological responses between animal models and humans [ [18] , [19] , [20] ].…”