Abdallah Basem M, Ali Enas M
Department of Biological Sciences, College of Science, King Faisal University, Al-Ahsa 31982, Saudi Arabia.
Department of Botany and Microbiology, Faculty of Science, Cairo University, Giza 12613, Egypt.
J Fungi (Basel). 2022 Apr 24;8(5):442. doi: 10.3390/jof8050442.
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 (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 with MIC 64 µg/mL and inhibited the radial growth of 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.
由于其独特的物理化学特性，金纳米颗粒在生物医学领域被广泛用于治疗多种疾病，包括癌症、炎症性疾病和免疫系统疾病。在本研究中，我们研究了使用（LH-AuNPs）乙醇叶提取物绿色合成的金纳米颗粒对小鼠侵袭性肺曲霉病（IPA）的治疗潜力。利用紫外/可见光谱、傅里叶变换红外光谱（FTIR）、透射电子显微镜（TEM）、X射线衍射（XRD）、能量色散X射线光谱（EDX）和zeta电位对生物合成的LH-AuNPs进行表征。通过MTT法（3-(4,5-二甲基-2-噻唑基)-2,5-二苯基-2H-四氮唑溴盐）、时间-杀菌试验和径向生长抑制试验测定LH-AuNPs的抗真菌活性。利用TEM和SEM研究LH-AuNPs的抗真菌作用模式。使用成熟的IPA小鼠模型研究LH-AuNPs对IPA的体内活性。LH-AuNPs对 表现出抗真菌活性，MIC为64μg/mL，与对照组相比，抑制 的径向生长30%。LH-AuNPs导致真菌菌丝变形和塌陷以及细胞壁退化。有趣的是，在MIC浓度下，LH-AuNPs在体外对培养的原代骨髓干细胞（BMSC）或A549人肺癌细胞系未显示任何细胞毒性。用LH-AuNPs治疗的IPA小鼠显示出显著的肺组织修复，且无任何体内细胞毒性。LH-AuNPs给药显示出对肺部真菌负荷和Gliotoxin产生的显著抑制。此外，LH-AuNPs抑制IPA诱导的促炎细胞因子产生，包括白细胞介素-1（IL-1）、白细胞介素-17（IL-17）和肿瘤坏死因子-α（TNF-α），并降低肺部氧化应激。总之，我们的数据表明LH-AuNPs是一种用于IPA的新型纳米颗粒疗法。
