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Effective Inhibition of Invasive Pulmonary Aspergillosis by Silver Nanoparticles Biosynthesized with Artemisia sieberi Leaf Extract.

ABSTRACT: Aspergillus fumigatus is one of the most common fungal pathogens that can cause a diversity of diseases ranging from invasive pulmonary aspergillosis (IPA) and aspergilloma to allergic syndromes. In this study, we investigated the antifungal effect of silver nanoparticles biosynthesized with Artemisia sieberi leaf extract (AS-AgNPs) against A. fumigatus in vitro and in vivo. The biosynthesized AS-AgNPs were characterized by imaging (transmission electron microscopy (TEM)), UV-VIS spectroscopy, X-ray diffraction (XRD), and Fourier transform infrared spectroscopy (FTIR). The microdilution method showed the antifungal activity of AS-AgNPs against A. fumigatus, with an MIC of 128 µg/mL. AS-AgNPs significantly inhibited the growth of hyphae in all directions, as imaged by SEM. Additionally, TEM on biofilm revealed invaginations of the cell membrane, a change in the vacuolar system, and the presence of multilamellar bodies within vacuoles. Interestingly, AS-AgNPs displayed low cytotoxicity on the A549 human lung cell line in vitro. Treatment of an invasive pulmonary aspergillosis (IPA) mouse model with AS-AgNPs demonstrated the potency of AS-AgNPs to significantly reduce lung tissue damage and to suppress the elevated levels of pro-inflammatory cytokines, tumor necrosis factor-alpha (TNF-α), interleukin-1 (IL-1), and interleukin-17 (IL-17). The therapeutic potential of AS-AgNPs was found to be due to their direct action to suppress the fungal burden and gliotoxin production in the lungs. In addition, AS-AgNPs reduced the oxidative stress in the lungs by increasing the enzymatic activities of catalase (CAT) and superoxide dismutase (SOD). Thus, our data indicate the biosynthesized AS-AgNPs as a novel antifungal alternative treatment against aspergillosis.

SUBMITTER: Ali EM

PROVIDER: S-EPMC8746907 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Gold nanoparticles are widely used in the biomedical field for the treatment of several diseases, including cancer, inflammatory diseases, and immune system disorders, due to their distinctive physicochemical characteristics. In this study, we investigated the therapeutic potential of green synthesized gold nanoparticles using ethanolic leaf extract of Leptadenia hastata (LH-AuNPs) against invasive pulmonary aspergillosis (IPA) in mice. UV/visible spectroscopy, Fourier transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM), X-ray diffraction (XRD), energy-dispersive X-ray spectroscopy (EDX), and zeta potential were used to characterize the biofabricated LH-AuNPs. Antifungal activity of LH-AuNPs was determined by MTT assay, (3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide), time-kill assay, and radial growth inhibition. TEM and SEM were used to examine the mode of the antifungal action of LH-AuNPs. The in vivo activity of LH-AuNPs against IPA was studied using a well-established IPA mouse model. LH-AuNPs excreted antifungal activity against Aspergillus fumigatus with MIC 64 µg/mL and inhibited the radial growth of A. fumigatus by 30% compared to the control. LH-AuNPs caused distortion and collapse of fungal hyphae and deterioration of cell walls. Interestingly, LH-AuNPs did not display any cytotoxicity on cultured primary bone marrow stem cells (BMSCs) or A549 human lung cell line in vitro at MIC concentration. IPA mice treated with LH-AuNPs displayed significant lung tissue repair without any in vivo cytotoxicity. LH-AuNPs administration showed significant suppression of fungal burden and gliotoxin production in the lung. In addition, LH-AuNPs inhibited IPA-induced pro-inflammatory cytokines production, including interleukin-1 (IL-1), interleukin-17 (IL-17), and tumor necrosis factor-alpha (TNF-α), and reduced oxidative stress in lung. In conclusion, our data provide LH-AuNPs as a novel nanoparticle therapy for IPA.

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Effective Inhibition of Invasive Pulmonary Aspergillosis by Silver Nanoparticles Biosynthesized with Artemisia sieberi Leaf Extract.

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