Toxicity evaluation of mesoporous silica particles Santa Barbara No. 15 amorphous in human umbilical vein endothelial cells: influence of particle morphology

Abstract

Morphology plays a vital role in determining the biological effects of silica nanoparticles (NPs), but its influence on the toxicity of silica NPs in endothelial cells (ECs) is still inconclusive. We synthesized five kinds of Santa Barbara 15 amorphous (SBA‐15) particles with different shapes and added them to human umbilical vein endothelial cells (HUVEC). After 24 After incubation and treatment with 100 ml, more than 80% of the cells are still alive. The microgram/ml of SBA‐15 indicates that SBA‐15 has high biocompatibility. Fibrous SBA‐15 (5) leads to the highest Si element concentration in HUVEC. No NP reduces the release of NO, and NO is an important signaling molecule in the vascular system. Only the aggregated spherical SBA‐15 (3) will moderately reduce the endothelial nitric oxide synthase (eNOS) protein. Regarding transcription factors regulating eNOS, we found that all SBA‐15 types significantly increased Kruppel‐like factor 2 (KLF2) protein, irregular SBA‐15 (1), non‐aggregated spherical SBA‐15 (2) and aggregation The spherical SBA‐15 (3) greatly reduces KLF4 by more than 50%. Overall, our results indicate that SBA‐15 with different morphologies can be internalized into HUVEC and only cause moderate cytotoxicity. All silica NPs have the smallest effect on the NO‐eNOS pathway, but the irregular spherical SBA‐15 reduces the eNOS modifier KLF4. The rod‐shaped SBA‐15 (4) seems to have higher biocompatibility because they are internalized and have negligible adverse effects on HUVEC. These results provide new evidence for the toxic effects of different forms of silica nanoparticles on HUVEC.

Potential roles of Kruppel‐like factors in mediating adverse vascular effects of nanomaterials: A review

“…At noncytotoxic concentrations, SBA‐15 particles increased KLF2 but decreased KLF4 proteins. However, NO signaling pathway was not influenced, that intracellular NO was not decreased, and eNOS proteins were only modestly decreased by the spherical particles (Teng et al, 2021).…”

Activation of KLF6 by titanate nanofibers and regulatory roles of KLF6 on ATF3 in the endothelial monolayer and mouse aortas

“…24,25 Teng et al reported that fibrous SiO 2 NMs at non-cytotoxic concentrations decreased KLF4 proteins in HUVECs. 26 Öner et al found that SWCNTs or amosite at non-cytotoxic concentrations altered KLF3 activity in bronchial epithelial cells through hypermethylation. 27 In addition, previous studies showed that NMs could modulate KLF activity even if the NMs were not acutely cytotoxic, but the influences of NMs on KLFs and the KLF-regulated downstream events still require more studies.…”

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

“…In particular, KLF2 and KLF4 are well‐known KLFs to regulate the generation of NO in vascular system (Cao, 2021; Fan et al, 2017). Previously, we and others reported that NMs altered KLF‐NO signaling pathways in endothelial cells (Li et al, 2020, 2021; Li, Tang, et al, 2019; Teng et al, 2021). Besides endothelial cells, NMs have also been shown to affect KLFs in vascular smooth muscle cells (Wang et al, 2018; Yang et al, 2019), lung epithelial cells (Öner et al, 2020) and brain organoids (Jiang et al, 2020), indicating that NMs could influence KLF signaling pathways in various in vitro models.…”

“…In this study, we found that both P25 particles and nanobelts decreased KLF2 and KLF4 expression to similar extent (Figure 8), which suggested that the morphology is not an important parameter. However, a recent study reported that fibrous SiO 2 materials were more potent to decrease KLF4 proteins in HUVECs compared with spheroid particles (Teng et al, 2021). Whether the morphologies of NMs will change the influences of NMs on KLFs may be dependent on the compositions of NMs, but this point should be investigated by further studies.…”

“…Recently, our group proposed that Kruppel‐like factors (TFs), transcription factors (TFs) with crucial regulatory roles in vascular biology, may be involved in NM‐induced endothelial activation (Cao, 2021). Recent studies already reported that many NMs, including multi‐walled nanotubes, halloysite nanotubes (Li, Liu, et al, 2019; Wu, Jiang, et al, 2020), gold (Au) nanorods (Li, Tang, et al, 2019), SiO 2 NMs (Teng et al, 2021), TiO 2 nanoparticles (NPs), titanate nanotubes and nanofibers (Li et al, 2020, 2021), affected KLF‐regulated NO signaling pathways in endothelial cells. Interestingly, we reported before that Ti‐based NMs altered the expression of KLFs in endothelial cells (Li et al, 2020) as well as vascular smooth muscle cells (Wang et al, 2018) even at non‐cytotoxic concentrations, indicating a need to re‐evaluate the influences of NMs composed of biocompatible elements on KLFs.…”