<p>Multi-Walled Carbon Nanotubes (MWCNTs) Activate Apoptotic Pathway Through ER Stress: Does Surface Chemistry Matter?</p>

Abstract

PurposePhysicochemical properties play a crucial role in determining the toxicity of multi-walled carbon nanotubes (MWCNTs). Recently we found that MWCNTs with longer length and smaller diameters could induce toxicity to human umbilical vein endothelial cells (HUVECs) through the activation of endoplasmic reticulum (ER) stress. In this study, we further investigated the possible contribution of hydroxylation and carboxylation to the cytotoxicity of MWCNTs.MethodsThe HUVECs were exposed to pristine (code XFM19), hydroxylated (code XFM20; content of hydroxyl groups 1.76 wt%) and carboxylated (code XFM21; content of carboxyl groups 1.23 wt%) MWCNTs, respectively. Then, the internalization, cytotoxicity, oxidative stress and activation of apoptosis-ER stress pathway were measured.ResultsIn consequence, all types of MWCNTs could be internalized into the HUVECs, and the cellular viability was significantly reduced to a similar level. Moreover, the MWCNTs increased intracellular reactive oxygen species (ROS) and decreased glutathione (GSH) to similar levels, indicating their capacity of inducing oxidative stress. The Western blot results showed that all types of MWCNTs reduced BCL-2 and increased caspase-3, caspase-8, cleaved caspase-3 and cleaved caspase-8. The expression of ER stress gene DNA damage-inducible transcript 3 (DDIT3) and protein level of chop were only significantly induced by XFM20 and XFM21, whereas protein level of p-chop was promoted by XFM19 and XFM21. In addition, the pro-survival gene XBP-1s was significantly down-regulated by all types of MWCNTs.ConclusionThese results suggested that MWCNTs could induce cytotoxicity to HUVECs via the induction of oxidative stress and apoptosis-ER stress, whereas a low degree of hydroxylation or carboxylation did not affect the toxicity of MWCNTs to HUVECs.

Influences of Unmodified and Carboxylated Carbon Nanotubes on Lipid Profiles in THP-1 Macrophages: A Lipidomics Study

“…17,23 These results indicated that unmodified and carboxylated MWCNTs were equally cytotoxic to THP-1 macrophages. Previous studies also reported that unmodified and carboxylated MWCNTs were equally cytotoxic to human endothelial cells, 24 THP-1 macrophages, 21 vascular smooth muscle cells, 25 and HepG2 cells, 26 although MWCNTs used in previous studies contained a much lower level of carboxyl groups compared with the MWCNTs used in this study (1.23 wt% vs 3.86 wt%). Hereby, our results indicated that even a relatively high degree of carboxylation did not change the cytotoxic potential of MWCNTs to THP-1 macrophages.…”

In Vitro Evaluation of DSPE-PEG (5000) Amine SWCNT Toxicity and Efficacy as a Novel Nanovector Candidate in Photothermal Therapy by Response Surface Methodology (RSM)

“…Many studies report that mild hyperthermia (42–45 °C) is optimal to induce apoptosis via mitochondrial damage and oxidative stress. Higher temperatures (≥52 °C) could damage normal cells and increase PTT adverse effects [ 64 , 65 ]. As a matter of fact, cell necrosis is temperature-dependent.…”

“…Acknowledging this, we first examined the in vitro toxicity of DSPE-PEG (5000) amine SWCNTs in vital organs including the liver and lungs. It is necessary to check if the concentrations of these nanomaterials are safe to be used in future biomedical applications or not [ 61 , 62 , 65 , 66 ]. The molecular weight and functional group charges of DSPE-PEG were assumed to play an important role in the biocompatibility improvement of DSPE-PEG amine SWCNTs [ 45 , 47 , 48 ].…”

Near‐infrared emission Cu, N‐doped carbon dots for human umbilical vein endothelial cell labeling and their biocompatibility in vitro

“…Direct contact of endothelial cells with NMs, such as carbon nanotubes (Y. Sun, Gong, & Cao, 2019; X. Zhao et al, 2019), CB NPs (G. Wang et al, 2019), ZnO NPs (Chen et al, 2014), TiO 2 NPs (Simon et al, 2017), and CdTe QDs (M. Yan et al, 2016), activated ER stress as the mechanism to induce cytotoxicity. In this study, we also found that CB NPs induced ER stress–apoptotic proteins (Figure 5), which could explain the cytotoxicity of CB NPs to HUVECs.…”