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.

Comparison of cytotoxicity of Ag/ZnO and Ag@ZnO nanocomplexes to human umbilical vein endothelial cells in vitro.

Novel metal and metal oxide-based nanocomplexes are being developed due to their superior properties compared with nanoparticles (NPs) based on single composition. In this study, we synthesized Ag-coated ZnO (Ag/ZnO) and Ag-doped ZnO (Ag@ZnO) NPs. The cytotoxicity and mechanisms associated with the synthesized NPs were investigated to understand the influence of Ag positions on biocompatibility of the NPs. After exposure to human umbilical vein endothelial cells (HUVECs), Ag/ZnO, Ag@ZnO, and ZnO NPs all significantly induced cytotoxicity, but the cytotoxic effects of Ag/ZnO and Ag@ZnO NPs were more modest in comparison with ZnO NPs. At cytotoxic concentrations, all NPs significantly induced intracellular Zn ions, which suggested a role of excessive Zn ions on cytotoxicity of NPs. All types of NPs significantly induced the expression of endoplasmic reticulum (ER) stress genes including DNA damage-inducible transcript 3 (DDIT3), X-box binding protein 1 (XBP-1), and ER to nucleus signaling 1 (ERN1), but Ag/ZnO and Ag@ZnO NPs were less effective to induce DDIT3 and XBP-1 expression compared with ZnO NPs. Not surprisingly, only ZnO NPs significantly induced the expression of caspase 3. Combined, the results from this study showed that Ag/ZnO and Ag@ZnO NPs were less cytotoxic and less potent to induce ER stress gene expression compared with ZnO NPs, but there were no significant differences between Ag/ZnO and Ag@ZnO NPs. Our results may provide novel understanding about the biocompatibility of Ag-ZnO nanocomplexes.

The toxicity of ZnO nanomaterials to HepG2 cells: the influence of size and shape of particles.

Understanding the possible role of physicochemical properties in determining the toxicity of ZnO nanomaterials (NMs) is crucial for the safe use of ZnO-based materials. In this study, we synthesized four types of ZnO NMs, and characterized them as ZnO nanorods (NRs; length 400-500 nm, diameter 150-200 nm), ZnO Mini-NRs (length 50-100 nm, diameter 15-20 nm), amorphous ZnO microspheres (a-ZnO MS) and crystalline ZnO MS (c-ZnO MS; the a/c-ZnO MS are nanoflowers with an extensive growth of sheet-like structures). ZnO NMs and ZnO Mini-NRs were significantly more cytotoxic than a/c-ZnO MS, and this trend was similar in both HepG2 cells and human umbilical vein endothelial cells. Intracellular reactive oxygen species was only modestly induced by c-ZnO MS, whereas intracellular Zn ions were dose-dependently increased in HepG2 cells by the exposure of all types of ZnO NMs. The expression of endoplasmic reticulum stress marker DDIT3 was induced following an order of ZnO NRs > a-ZnO MS > c-ZnO MS > ZnO Mini-NRs, and the apoptosis gene CASP12 was induced following an order of a-ZnO MS > ZnO NRs > c-ZnO MS > ZnO Mini-NRs. Combined, these results suggested that ZnO NM-induced cytotoxicity and expression of endoplasmic reticulum stress-apoptosis genes could be influenced by the size and shape of ZnO NMs.

TiO2 nanosheets promote the transformation of vascular smooth muscle cells into foam cells in vitro and in vivo through the up-regulation of nuclear factor kappa B subunit 2.

Titanium dioxide (TiO2) nanomaterials have been shown to promote atherosclerosis through endothelial dysfunction. This study investigated the toxicity of TiO2 nanosheets (NSs) to vascular smooth muscle cells (VSMCs), one of the pivotal cells involved in all stages of atherosclerosis. Only a high concentration of TiO2 NSs (128 µg/mL) modestly induced cytotoxicity by decreasing thiols. RNA-sequencing data revealed that 64 µg/mL TiO2 NSs significantly down-regulated 94 genes and up-regulated 174 genes, respectively. Gene ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways related to SMC function and lipid metabolism were altered. TiO2 NSs increased nuclear factor kappa B subunit 2 (NFKB2), which led to a decrease in VSMC marker actin alpha 2, smooth muscle (ACTA2). On the other hand, macrophage marker CD36 and fatty acid synthase (FASN) proteins were increased. Additionally, TiO2 NSs induced inflammatory cytokines and lipid accumulation, and these effects were curtailed by NFKB inhibitor - triptolide. Furthermore, repeated TiO2 NS injection (5 mg/kg BW, once a day for 5 continuous days) into ICR mice led to increased NFKB2, CD36 and FASN, with a decreased ACTA2. Our results suggested that TiO2 NSs promoted the transformation of VSMCs into foam cells through the up-regulation of NFKB2.

Ti-doped α-Fe2O3 nanorods with controllable morphology by carbon layer coating for enhanced photoelectrochemical water oxidation.

Ti-doped α-Fe2O3 nanorods (NRs) with carbon layer coating were fabricated for photoelectrochemical (PEC) water oxidation. The α-Fe2O3 NRs were grown on the surface of a Ti foil substrate by hydrothermal synthesis. Ti4+ was diffused from the Ti substrate and doped into the α-Fe2O3 NRs by sintering at 800 °C. The presence of Fe2+ in the α-Fe2O3 lattice was achieved by annealing the NRs in a lack of oxygen atmosphere, e.g. in argon. The co-existence of Ti4+ and Fe2+ results in significant enhancement of the PEC performance compared with the hematite NRs obtained by annealing in air, showing the absence of Fe2+. The carbon layer coating was conducted by the carbonization of glucose. Impressively, the coated carbon layer can not only facilitate the charge transfer of the photogenerated carriers but also effectively restrain the structural aggregation of the NRs upon high temperature sintering. The carbon layer coated NRs exhibited 1.2 times higher photocurrent density than the uncoated NRs due to the reduced charge recombination and well-distinct NR structures.