Comparison of P25 and nanobelts on Kruppel-like factor-mediated nitric oxide pathways in human umbilical vein endothelial cells.

Recently, we reported that titanium dioxide (TiO2 ) materials activated endothelial cells via Kruppel-like factor (KLF)-mediated nitric oxide (NO) dysfunction, but the roles of physical properties of materials are not clear. In this study, we prepared nanobelts from P25 particles and compared their adverse effects to human umbilical vein endothelial cells (HUVECs). TiO2 nanobelts had belt-like morphology but comparable surface areas as P25 particles. When applied to HUVECs, P25 particles or nanobelts did not induce cytotoxicity, although nanobelts were much more effective to increase intracellular Ti element concentrations compared the same amounts of P25 particles. Only nanobelts significantly induced THP-1 adhesion onto HUVECs. Consistently, nanobelts were more significant to induce the expression of intracellular adhesion molecule-1 (ICAM1) and the release of soluble ICAM-1 (sICAM-1), indicating that nanobelts were more potent to induce endothelial activation in vitro. As the mechanisms for endothelial activation, both P25 and nanobelts reduced the generation of intracellular NO as well as the expression of NO regulators KLF2 and KLF4. Combined, the results from this study indicated that the different morphologies of P25 particles and nanobelts only changed their internalization into HUVECs but showed minimal impact on KLF-mediated NO signaling pathways.

Effects of epigallocatechin gallate on the stability, dissolution and toxicology of ZnO nanoparticles.

Previously we reported the cytoprotective effects of polyphenols rich in hydroxyl groups against ZnO nanoparticles (NPs). This study used RNA-sequencing to evaluate the toxicity of ZnO NPs and epigallocatechin gallate (EGCG) to 3D Caco-2 spheroids. EGCG altered the colloidal stability of ZnO NPs, shown as the changes of atomic force microscopic height, solubility in cell culture medium, and hydrodynamic sizes. EGCG almost completely reversed ZnO NP-induced cytotoxicity, and consistently, alleviated ZnO NP-induced gene ontology (GO) terms and genes related with apoptosis. EGCG also modestly decreased intracellular Zn ions and changed GO terms and genes related with endocytosis/exocytosis in ZnO NP-exposed spheroids. Meanwhile, EGCG changed ZnO NP-induced alteration of GO terms and genes related with the functions of mitochondria, endoplasmic reticulum and lysosomes. We concluded that EGCG alleviated the cytotoxicity of ZnO NPs to 3D Caco-2 spheroids by altering NPs' colloidal properties and the pathways related with internalization and organelle dysfunction.

Comparison of toxicity of Ti3 C2 and Nb2 C Mxene quantum dots (QDs) to human umbilical vein endothelial cells.

Recently, we developed highly fluorescent Ti3 C2 and Nb2 C Mxene quantum dots (QDs) for labeling of in vitro models. However, the mechanism of the toxicity of the prepared QDs was not explored before. In this study, we addressed the possible mechanism associated with cytotoxicity of the QDs to human umbilical vein endothelial cells (HUVECs). Exposure to up to 100 µg/ml Ti3 C2 but not Nb2 C QDs for 24 h significantly induced cytotoxicity. The exposure also increased intracellular Ti and Nb elements, indicating the internalization of both types of QDs. None of the QDs promoted interleukin 6 (IL-6) and IL-8 releases. Rather, Ti3 C2 QDs significantly reduced IL-6 and IL-8 release, indicating that the toxicity of Ti3 C2 QDs was not due to elevated inflammatory responses. Exposure to Ti3 C2 but not Nb2 C QDs resulted in increased LC3B-II/I ratio and beclin-1 proteins, biomarkers of autophagy, as well as the accumulation of autophagic substance p62. Ti3 C2 QDs also more effectively promoted pro-caspase 3 but not pro-caspase 8 compared with Nb2 C QDs. Furthermore, pre-treatment with autophagic modulators altered the cytotoxicity of Ti3 C2 QDs, which further confirmed the role of autophagic dysfunction in Ti3 C2 QD-induced toxicity to HUVECs. In conclusion, the results from this study suggested that high levels of Ti3 C2 QDs could induce cytotoxicity to HUVECs by inducing the dysfunction of autophagy. Nb2 C QDs appeared to be more biocompatible to HUVECs compared with Ti3 C2 QDs at the same mass concentrations, which suggested a role of composition of Mxene QDs to determine their toxicity to human endothelial cells.