Acute exposure to silica nanoparticles aggravate airway inflammation: different effects according to surface characteristics

Abstract

Silica nanoparticles (SNPs) are widely used in many scientific and industrial fields despite the lack of proper evaluation of their potential toxicity. This study examined the effects of acute exposure to SNPs, either alone or in conjunction with ovalbumin (OVA), by studying the respiratory systems in exposed mouse models. Three types of SNPs were used: spherical SNPs (S-SNPs), mesoporous SNPs (M-SNPs), and PEGylated SNPs (P-SNPs). In the acute SNP exposure model performed, 6-week-old BALB/c female mice were intranasally inoculated with SNPs for 3 consecutive days. In the OVA/SNPs asthma model, the mice were sensitized two times via the peritoneal route with OVA. Additionally, the mice endured OVA with or without SNP challenges intranasally. Acute SNP exposure induced significant airway inflammation and airway hyper-responsiveness, particularly in the S-SNP group. In OVA/SNPs asthma models, OVA with SNP-treated group showed significant airway inflammation, more than those treated with only OVA and without SNPs. In these models, the P-SNP group induced lower levels of inflammation on airways than both the S-SNP or M-SNP groups. Interleukin (IL)-5, IL-13, IL-1β and interferon-γ levels correlated with airway inflammation in the tested models, without statistical significance. In the mouse models studied, increased airway inflammation was associated with acute SNPs exposure, whether exposed solely to SNPs or SNPs in conjunction with OVA. P-SNPs appear to be relatively safer for clinical use than S-SNPs and M-SNPs, as determined by lower observed toxicity and airway system inflammation.

Figure 1

Transmission electron microscopy images of (a) S-SNPs, (b) M-SNPs and (c) P-SNPs. M-SNP, mesoporous silica nanoparticle; P-SNP, PEGylated silica nanoparticle; S-SNP, spherical silica nanoparticle.

Figure 2

Experiment scheme. (a) Experiment 1: acute SNP exposure models. (b) Experiment 2: acute exposure to SNPs with OVA-induced asthma models. exp, experiment; IN, intranasal inoculation; IP, intraperitoneal injection; OVA, ovalbumin; SNP, silica nanoparticle.

Figure 3

The airway inflammation as demonstrated in (a) bronchoalveolar lavage fluid (BALF) and (b) airway hyper-responsiveness in acute SNP exposure models. *P<0.05 between two variables; ^#P<0.05 compared with others. M-SNP, mesoporous silica nanoparticle; P-SNP, PEGylated silica nanoparticle; R_L, resistance of lung; S-SNP, spherical silica nanoparticle.

Figure 4

Histological findings of lungs representing peribronchial and perivascular tissues in the (a) control group, (b) S-SNP group, (c) M-SNP group and the (d) P-SNP group. M-SNP, mesoporous silica nanoparticle; P-SNP, PEGylated silica nanoparticle; S-SNP, soluble silica nanoparticle.

Figure 5

Cytokine levels of (a) IL-5, (b) IL-13, (c) IL-1β and (d) IFN-γ in acute SNP exposure models. IFN-γ, interferon-γ IL-5, interleukin-5; M-SNP, mesoporous silica nanoparticle; P-SNP, PEGylated silica nanoparticle; S-SNP, spherical silica nanoparticle.

Figure 6

Airway inflammation as determined by analysis of (a) bronchoalveolar lavage fluid (BALF) and (b) airway hyper-responsiveness in OVA/SNPs asthma models. *P<0.05 between two variables; ^#P<0.05 compared with others. M-SNP, mesoporous silica nanoparticle; OVA, ovalbumin; P-SNP, PEGylated silica nanoparticle; R_L, Resistance of lung; S-SNP, spherical silica nanoparticle.

Figure 7

Histological findings in peribronchial and perivascular tissues of the (a) control group, (b) OVA-only group, (c) S-SNP group, (d) M-SNP group and (e) P-SNP group. M-SNP, mesoporous silica nanoparticle; P-SNP, PEGylated silica nanoparticle; S-SNP, spherical silica nanoparticle.

Figure 8

Cytokine levels including (a) IL-5, (b) IL-13, (c) IL-1β and (d) IFN-γ in OVA/SNPs asthma models. ^#P<0.05 compared with others. IFN-γ, interferon-γ IL-5, interleukin-5; M-SNP, mesoporous silica nanoparticle; P-SNP, PEGylated silica nanoparticle; S-SNP, spherical silica nanoparticle.