Oxidative stress- and mitochondrial dysfunction-mediated cytotoxicity by silica nanoparticle in lung epithelial cells from metabolomic perspective

Zhao, Xinying; Abulikemu, Alimire; Lv, Songqing; Qi, Yi; Duan, Junchao; Zhang, Jie; Chen, Rui; Guo, Caixia; Li, Yanbo; Sun, Zhiwei

doi:10.1016/j.chemosphere.2021.129969

Cited by 60 publications

(23 citation statements)

References 91 publications

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“…6 ). This finding is in good agreement with observations from previous studies [ 62 , 63 ], where SiO 2 NP-induced cellular damage was attributed to their mitochondrial dysfunction.…”

Section: Discussionsupporting

confidence: 93%

Mechanistic study of silica nanoparticles on the size-dependent retinal toxicity in vitro and in vivo

Zhang

Zhao

et al. 2022

J Nanobiotechnol

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Background Silica nanoparticles (SiO2 NPs) are extensively applied in the biomedical field. The increasing medical application of SiO2 NPs has raised concerns about their safety. However, studies on SiO2 NP-induced retinal toxicity are lacking. Methods We investigated the retinal toxicity of SiO2 NPs with different sizes (15 and 50 nm) in vitro and in vivo along with the underlying mechanisms. The cytotoxicity of SiO2 NPs with different sizes was assessed in R28 human retinal precursor cells by determining the ATP content and LDH release. The cell morphologies and nanoparticle distributions in the cells were analyzed by phase-contrast microscopy and transmission electron microscopy, respectively. The mitochondrial membrane potential was examined by confocal laser scanning microscopy. The retinal toxicity induced by SiO2 NPs in vivo was examined by immunohistochemical analysis. To further investigate the mechanism of retinal toxicity induced by SiO2 NPs, reactive oxygen species (ROS) generation, glial cell activation and inflammation were monitored. Results The 15-nm SiO2 NPs were found to have higher cytotoxicity than the larger NPs. Notably, the 15-nm SiO2 NPs induced retinal toxicity in vivo, as demonstrated by increased cell death in the retina, TUNEL-stained retinal cells, retinal ganglion cell degeneration, glial cell activation, and inflammation. In addition, The SiO2 NPs caused oxidative stress, as demonstrated by the increase in the ROS indicator H2DCF-DA. Furthermore, the pretreatment of R28 cells with N-acetylcysteine, an ROS scavenger, attenuated the ROS production and cytotoxicity induced by SiO2 NPs. Conclusions These results provide evidence that SiO2 NPs induce size-dependent retinal toxicity and suggest that glial cell activation and ROS generation contribute to this toxicity. Graphical Abstract

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“…6 ). This finding is in good agreement with observations from previous studies [ 62 , 63 ], where SiO 2 NP-induced cellular damage was attributed to their mitochondrial dysfunction.…”

Section: Discussionsupporting

confidence: 93%

Mechanistic study of silica nanoparticles on the size-dependent retinal toxicity in vitro and in vivo

Zhang

Zhao

et al. 2022

J Nanobiotechnol

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“…Indeed, such analysis confirms a moderate and transient mitochondrial damage (arrows): the known cristae rupture and disappearance [ 19 ] is almost absent and their scarce evidences are strictly limited to a restricted area of the mitochondrion (arrows): this event does not represent a key end-point of SiNPs nanotoxicity but the starting point for MDV formation. Presently, MDV trafficking is now included among mitochondrial quality control (MQC) pathways, possibly operating via mitochondrial–lysosomal contacts [ 20 ].…”

Section: Resultsmentioning

confidence: 99%

Fluorescent Silica Nanoparticles Targeting Mitochondria: Trafficking in Myeloid Cells and Application as Doxorubicin Delivery System in Breast Cancer Cells

Sola

Montanari

Fiorani

et al. 2022

IJMS

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Fluorescent silica nanoparticles (SiNPs) appear to be a promising imaging platform, showing a specific subcellular localization. In the present study, we first investigated their preferential mitochondrial targeting in myeloid cells, by flow cytometry, confocal microscopy and TEM on both cells and isolated mitochondria, to acquire knowledge in imaging combined with therapeutic applications. Then, we conjugated SiNPs to one of the most used anticancer drugs, doxorubicin (DOX). As an anticancer agent, DOX has high efficacy but also an elevated systemic toxicity, causing multiple side effects. Nanostructures are usually employed to increase the drug circulation time and accumulation in target tissues, reducing undesired cytotoxicity. We tested these functionalized SiNPs (DOX-NPs) on breast cancer cell line MCF-7. We evaluated DOX-NP cytotoxicity, the effect on the cell cycle and on the expression of CD44 antigen, a molecule involved in adhesion and in tumor invasion, comparing DOX-NP to free DOX and stand-alone SiNPs. We found a specific ability to release a minor amount of CD44+ extracellular vesicles (EVs), from both CD81 negative and CD81 positive pools. Modulating the levels of CD44 at the cell surface in cancer cells is thus of great importance for disrupting the signaling pathways that favor tumor progression.

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“…In parallel to ROS release, HO-1 mRNA and protein levels were significantly increased after exposure to 50 nm silica particles at 50 µg/mL [ 91 ], with induction shown to involve the Nrf-2-ERK MAP kinase signaling pathway in human BEAS-2B cells [ 125 ]. Other oxidative stress markers were also perturbed in a dose-dependent manner in human epithelial cells: lipid peroxidation was significantly increased, whereas intracellular GSH was slightly depleted [ 110 , 126 ]. However, oxidative stress is only detected at high doses.…”

Section: Biological Effects Of Micro- and Nanometric Crystalline Or A...mentioning

confidence: 99%

Pulmonary Toxicity of Silica Linked to Its Micro- or Nanometric Particle Size and Crystal Structure: A Review

et al. 2022

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Silicon dioxide (SiO2) is a mineral compound present in the Earth’s crust in two mineral forms: crystalline and amorphous. Based on epidemiological and/or biological evidence, the pulmonary effects of crystalline silica are considered well understood, with the development of silicosis, emphysema, chronic bronchitis, or chronic obstructive pulmonary disease. The structure and capacity to trigger oxidative stress are recognized as relevant determinants in crystalline silica’s toxicity. In contrast, natural amorphous silica was long considered nontoxic, and was often used as a negative control in experimental studies. However, as manufactured amorphous silica nanoparticles (or nanosilica or SiNP) are becoming widely used in industrial applications, these paradigms must now be reconsidered at the nanoscale (<100 nm). Indeed, recent experimental studies appear to point towards significant toxicity of manufactured amorphous silica nanoparticles similar to that of micrometric crystalline silica. In this article, we present an extensive review of the nontumoral pulmonary effects of silica based on in vitro and in vivo experimental studies. The findings of this review are presented both for micro- and nanoscale particles, but also based on the crystalline structure of the silica particles.

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Oxidative stress- and mitochondrial dysfunction-mediated cytotoxicity by silica nanoparticle in lung epithelial cells from metabolomic perspective

Cited by 60 publications

References 91 publications

Mechanistic study of silica nanoparticles on the size-dependent retinal toxicity in vitro and in vivo

Mechanistic study of silica nanoparticles on the size-dependent retinal toxicity in vitro and in vivo

Fluorescent Silica Nanoparticles Targeting Mitochondria: Trafficking in Myeloid Cells and Application as Doxorubicin Delivery System in Breast Cancer Cells

Pulmonary Toxicity of Silica Linked to Its Micro- or Nanometric Particle Size and Crystal Structure: A Review

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