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.

Therapeutic Potential of Green Synthesized Gold Nanoparticles Using Extract of Leptadenia hastata against Invasive Pulmonary Aspergillosis

“…Our results demonstrated the effective inhibitory effect of LH-AuNPs on IPA-induced inflammatory cytokines. Similarly, we have recently reported the therapeutic potential of a single dose of green synthesized AS-AgNPs to suppress IPA-induced pro-inflammatory cytokines and lung tissue damage in mice [ 14 ]. The anti-inflammatory properties of Au-NPs were reported in vitro and in vivo in many studies to be mediated by antioxidant properties [ 71 , 72 ].…”

“…A strain of A. fumigatus was formerly isolated by our group from an immunocompromised patient with IPA [ 14 ]. Fungal suspension was prepared by cultivating A. fumigatus on Peptone Yeast Extract Agar (PYG) medium for 5 days at 35 °C, and the conidia were harvested as described previously [ 22 ].…”

“…Green synthesis of nanoparticles using biological extracts has been developed to provide large-scale production, where mild reaction conditions without additional reducing agents and stabilizers were applied that minimize the hazardous wastes and reduce the costs of nanoparticle production [ 13 ]. We have recently reported that the green synthesis of silver nanoparticles (AgNPs) using plant extracts could effectively produce nanoparticles with antimicrobial effects against C. albicans and A. fumigatus in vitro and in vivo [ 14 , 15 ].…”

Therapeutic Effect of Green Synthesized Silver Nanoparticles Using Erodium glaucophyllum Extract against Oral Candidiasis: In Vitro and In Vivo Study

“…As compared to chemically synthesized AgNPs, the green synthesized AgNPs using different plant extracts showed antimicrobial activity with low cytotoxicity in human and animal cells when applied at MIC values [12,13,[65][66][67]. Shape, size, and concentration are important factors that affect the toxicity level of AgNPs.…”

Recent Advances in Nano-Formulations for Skin Wound Repair Applications

“…97,99,100 A large number of studies have shown that by reducing the expression levels of proinflammatory cytokines, such as interleukin 6 (IL-6), tumor necrosis factor-α (TNF-α) and so on, AgNPs can inhibit a variety of pathogenic microorganisms, including fungi, different types of bacteria and even viruses and have shown excellent anti-inflammatory activity, which means that they can be used to prevent or reduce wound infection. [101][102][103][104] Similarly, in diabetic wounds, AgNPs accelerate wound healing by activating the proliferation and migration of keratinocytes and helping fibroblasts differentiate into myofibroblasts, thus promoting wound contraction and accelerating the healing of diabetic ulcers. AgNPs are widely used in wound healing because they accelerate cell proliferation, possess broad-spectrum antibacterial and anti-inflammatory activities, and promote wound healing (Figure 3A).…”