Comparison of toxicity of Ti₃C₂ and Nb₂C Mxene quantum dots (QDs) to human umbilical vein endothelial cells

Abstract

Recently, we developed highly fluorescent Ti3C2 and Nb2C 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 Ti3C2 but not Nb2C 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, Ti3C2 QDs significantly reduced IL‐6 and IL‐8 release, indicating that the toxicity of Ti3C2 QDs was not due to elevated inflammatory responses. Exposure to Ti3C2 but not Nb2C QDs resulted in increased LC3B‐II/I ratio and beclin‐1 proteins, biomarkers of autophagy, as well as the accumulation of autophagic substance p62. Ti3C2 QDs also more effectively promoted pro‐caspase 3 but not pro‐caspase 8 compared with Nb2C QDs. Furthermore, pre‐treatment with autophagic modulators altered the cytotoxicity of Ti3C2 QDs, which further confirmed the role of autophagic dysfunction in Ti3C2 QD‐induced toxicity to HUVECs. In conclusion, the results from this study suggested that high levels of Ti3C2 QDs could induce cytotoxicity to HUVECs by inducing the dysfunction of autophagy. Nb2C QDs appeared to be more biocompatible to HUVECs compared with Ti3C2 QDs at the same mass concentrations, which suggested a role of composition of Mxene QDs to determine their toxicity to human endothelial cells.

A comparative study of toxicity of graphdiyne and graphene oxide to human umbilical vein endothelial cells

“…Meanwhile, the internalization of carbon nanotubes led to the cytotoxicity of ECs (Li et al, 2019; Suzuki et al, 2016; Valentini et al, 2018). High levels of Ti 2 C Mxene, novel 2D NMs, also induced cytotoxicity to HUVECs (Gu et al, 2021). In this study, the results suggested that GDY, novel carbon‐based 2D NMs, was as cytotoxic as GO based on the same mass concentrations.…”

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

“…As shown Figure 6, HUVECs were successfully labeled by Cu, N‐doped CDs with strong red fluorescence. Recently, we developed highly fluorescent MXene QDs to label in vitro models, but they also induced strong cytotoxic effects (Gu et al, 2020; Guan et al, 2019; Q. Xu et al, 2020; X. Yan, Ma, et al, 2020). Here, the data reported in this study suggested that Cu, N‐doped CDs were more biocompatible for bio‐imaging purposes (Figure 4).…”

“…However, we recently developed novel MXene QDs. Although they could be used to label cells and organoids (Guan et al, 2019; Q. Xu et al, 2020; X. Yan, Ma, et al, 2020), they still induced severe cytotoxicity to endothelial cells (Gu et al, 2020). On the basis of previous observations, we are developing high‐fluorescent QDs based on other materials.…”

Fabrication of Smart Tantalum Carbide MXene Quantum Dots with Intrinsic Immunomodulatory Properties for Treatment of Allograft Vasculopathy

“…Endothelial toxicity can therefore significantly limit the future biomedical applications of nanomaterials. [23] Furthermore, previous studies have reported that other forms of MXenes, such as Ti 3 C 2 T x MXenes, can increase cellular ROS levels, create oxidative stress to nearby cells, and cause cellular damage. [19,[39][40][41] This increase in ROS also induces the release of proinflammatory cytokines from resident tissue macrophages and interferes with anti-inflammatory and immunomodulatory properties of implanted biomaterials in the body.…”