Concentration‐dependent cytokine responses of silica nanoparticles and role of ROS in human lung epithelial cells

Subunit vaccines generally proceed through a 4-step in vivo cascade—the DUMP cascade—to generate potent cell-mediated immune responses: (1) drainage to lymph nodes; (2) uptake by dendritic cells (DCs); (3) maturation of DCs; and (4) Presentation of peptide-MHC I complexes to CD8+ T cells. How the physical properties of vaccine carriers such as mesoporous silica nanoparticles (MSNs) influence this cascade is unclear. We fabricated 80-nm MSNs with different pore sizes (7.8 nm, 10.3 nm, and 12.9 nm) and loaded them with ovalbumin antigen. Results demonstrated these MSNs with different pore sizes were equally effective in the first three steps of the DUMP cascade, but those with larger pores showed higher cross-presentation efficiency (step 4). Consistently, large-pore MSNs loaded with B16F10 tumor antigens yielded the strongest antitumor effects. These results demonstrate the promise of our lymph node-targeting large-pore MSNs as vaccine-delivery vehicles for immune activation and cancer vaccination.

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“…This is consistent with the results of cell toxicity (Fig. 3A), as ROS is often regarded as a key factor in toxicity (37,38).…”

Section: Discussionsupporting

confidence: 92%

The pore size of mesoporous silica nanoparticles regulates their antigen delivery efficiency

et al. 2020

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“…Both types of particles induce cytotoxic, genotoxic and pro-inflammatory acute responses [1,4,8]. In previous studies we have investigated SiNP-induced cytotoxicity, cytokine gene expression and release as well as underlying signalling pathways involved, in lung epithelial cells and macrophages in mono-cultures [11][12][13][14].…”

Section: Introductionmentioning

confidence: 99%

Pro-inflammatory effects of crystalline- and nano-sized non-crystalline silica particles in a 3D alveolar model

et al. 2020

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Background: Silica nanoparticles (SiNPs) are among the most widely manufactured and used nanoparticles. Concerns about potential health effects of SiNPs have therefore risen. Using a 3D tri-culture model of the alveolar lung barrier we examined effects of exposure to SiNPs (Si10) and crystalline silica (quartz; Min-U-Sil) in the apical compartment consisting of human alveolar epithelial A549 cells and THP-1-derived macrophages, as well as in the basolateral compartment with Ea.hy926 endothelial cells. Inflammation-related responses were measured by ELISA and gene expression. Results: Exposure to both Si10 and Min-U-Sil induced gene expression and release of CXCL8, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), interleukin-1α (IL-1α) and interleukin-1β (IL-1β) in a concentration-dependent manner. Cytokine/chemokine expression and protein levels were highest in the apical compartment. Si10 and Min-U-Sil also induced expression of adhesion molecules ICAM-1 and E-selectin in the apical compartment. In the basolateral endothelial compartment we observed marked, but postponed effects on expression of all these genes, but only at the highest particle concentrations. Geneexpressions of heme oxygenase-1 (HO-1) and the metalloproteases (MMP-1 and MMP-9) were less affected. The IL-1 receptor antagonist (IL-1RA), markedly reduced effects of Si10 and Min-U-Sil exposures on gene expression of cytokines and adhesion molecules, as well as cytokine-release in both compartments. Conclusions: Si10 and Min-U-Sil induced gene expression and release of pro-inflammatory cytokines/adhesion molecules at both the epithelial/macrophage and endothelial side of a 3D tri-culture. Responses in the basolateral endothelial cells were only induced at high concentrations, and seemed to be mediated by IL-1α/β released from the apical epithelial cells and macrophages.

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“…In recent decades, oxidative stress caused by NMs has garnered increasing attention [ 51 , 52 , 53 ]. In particular, the role that oxidative stress plays in the organs damage caused by NMs has aroused considerate concerns by many researchers [ 54 , 55 , 56 ]. In the present study, CZON was found to potentially cause the oxidative stress to the liver and lung tissues, indicating that the liver and lung might be the major target organs of CZON after intravenous injection.…”

Section: Discussionmentioning

confidence: 99%

Cu-Doped-ZnO Nanocrystals Induce Hepatocyte Autophagy by Oxidative Stress Pathway

et al. 2021

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As a novel nanomaterial for cancer therapy and antibacterial agent, Cu-doped-ZnO nanocrystals (CZON) has aroused concern recently, but the toxicity of CZON has received little attention. Results of hematology analysis and blood biochemical assay showed that a 50 mg/kg dosage induced the increase in white blood cells count and that the concentration of alanine aminotransferase (ALT), superoxide dismutase (SOD), catalase (CAT), and Malonaldehyde (MDA) in the serum, liver, and lungs of the CZON group varied significantly from the control mice. Histopathological examinations results showed inflammation and congestion in the liver and lung after a single injection of CZON at 50 mg/kg. A transmission electron microscope (TEM) result manifested the autolysosome of hepatocyte of mice which received CZON at 50 mg/kg. The significant increase in LC3-II and decrease in p62 of hepatocyte in vivo could be seen in Western blot. These results indicated that CZON had the ability to induce autophagy of hepatocyte. The further researches of mechanism of autophagy revealed that CZON could produce hydroxyl radicals measured by erythrocyte sedimentation rate (ESR). The result of bio-distribution of CZON in vivo, investigated by ICP-OES, indicated that CZON mainly accumulated in the liver and two spleen organs. These results suggested that CZON can induce dose-dependent toxicity and autophagy by inducing oxidative stress in major organs. In summary, we investigated the acute toxicity and biological distribution after the intravenous administration of CZON. The results of body weight, histomorphology, hematology, and blood biochemical tests showed that CZON had a dose-dependent effect on the health of mice after a single injection. These results indicated that CZON could induce oxidative damage of the liver and lung by producing hydroxyl radicals at the higher dose.

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Concentration‐dependent cytokine responses of silica nanoparticles and role of ROS in human lung epithelial cells

Cited by 22 publications

References 54 publications

The pore size of mesoporous silica nanoparticles regulates their antigen delivery efficiency

The pore size of mesoporous silica nanoparticles regulates their antigen delivery efficiency

Pro-inflammatory effects of crystalline- and nano-sized non-crystalline silica particles in a 3D alveolar model

Cu-Doped-ZnO Nanocrystals Induce Hepatocyte Autophagy by Oxidative Stress Pathway

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