Key Laboratory of Environment-Friendly Chemistry and Application of Ministry of Education, Laboratory of Biochemistry, College of Chemistry, Xiangtan University, Xiangtan 411105, China.
Department of Hygiene Inspection & Quarantine Science, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, Guangdong 510515, China.
Toxicol In Vitro. 2020 Feb;62:104689. doi: 10.1016/j.tiv.2019.104689. Epub 2019 Oct 17.
Titanate nanotubes (TiNTs) have been considered as biocompatible nanomaterials (NMs) for biomedical uses. Hereby, we compared the toxicity of TiNTs and TiO nanoparticles (NPs) to human umbilical vein endothelial cells (HUVECs). Our results showed that TiNTs were less effectively internalized into HUVECs compared with TiO NPs, but none of the NMs induced cytotoxicity or activation of endoplasmic reticulum (ER) stress biomarkers. In addition, intracellular reactive oxygen species (ROS) was only modestly induced by TiNTs and TiO NPs. However, both types of NMs significantly promoted the protein levels of vascular cell adhesion molecule-1 (VCAM-1). TiNTs also promoted the release of soluble (sVCAM-1), but THP-1 monocyte adhesion onto HUVECs was only induced by TiO NPs. TiNTs decreased the production of NO, associated with a decrease of protein levels of endothelial NO synthase (eNOS). The transcription factors of eNOS, including kruppel-like factor 2 (KLF2) and KLF4, were more effectively down-regulated by TiNTs compared with TiO NPs. In conclusion, our results indicated that TiNTs, albeit not cytotoxic, might impair NO signaling pathway in human endothelial cells leading to the activation of endothelial cells.
钛酸盐纳米管 (TiNTs) 已被认为是用于生物医学用途的生物相容性纳米材料 (NMs)。在此，我们比较了 TiNTs 和 TiO2 纳米颗粒 (NPs) 对人脐静脉内皮细胞 (HUVECs) 的毒性。我们的结果表明，与 TiO2 NPs 相比，TiNTs 较少有效地被 HUVECs 内化，但两种 NM 均未诱导细胞毒性或内质网 (ER) 应激生物标志物的激活。此外，细胞内活性氧物种 (ROS) 仅被 TiNTs 和 TiO2 NPs 适度诱导。然而，这两种类型的 NM 均显著促进血管细胞黏附分子-1 (VCAM-1) 的蛋白水平。TiNTs 还促进了可溶性 (sVCAM-1) 的释放，但仅 TiO2 NPs 诱导 THP-1 单核细胞黏附到 HUVECs。TiNTs 降低了 NO 的产生，与内皮型一氧化氮合酶 (eNOS) 的蛋白水平降低有关。eNOS 的转录因子，包括 Kruppel 样因子 2 (KLF2) 和 KLF4，与 TiO2 NPs 相比，TiNTs 更有效地下调。总之，我们的结果表明，TiNTs 虽然没有细胞毒性，但可能会损害人内皮细胞中的 NO 信号通路，导致内皮细胞的激活。
