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基于积雪草制备的 MgONPs 的抗菌、抗癌潜力评价及其在模型膜中的翻转酶诱导泄漏

Evaluation of antimicrobial, anticancer potential and Flippase induced leakage in model membrane of Centella asiatica fabricated MgONPs.

机构信息

Nanotoxicology Laboratory, Lab#312, School of Environmental Sciences, Jawaharlal Nehru University, New Delhi 110067, India.

Biochemistry and Environmental Toxicology Laboratory, Lab#103, School of Environmental Sciences, Jawaharlal Nehru University, New Delhi 110067, India.

出版信息

Biomater Adv. 2022 Jul;138:212855. doi: 10.1016/j.bioadv.2022.212855. Epub 2022 May 13.

DOI:10.1016/j.bioadv.2022.212855
PMID:35913247
Abstract

The use of chemically synthesized nanoparticles and crude plant extracts as antimicrobial -anticancer agents have many limitations. In this study, we have used Centella asiatica extract (CaE) having relatively less explored but tremendous medicinal properties, as reducing and stabilizing agents to green synthesize magnesium oxide nanoparticles (MgONPs) using magnesium nitrate. In comparison to the bulk material, capabilities of Ca-MgONPs as an improved antibacterial, antifungal, and anticancer agent in human prostatic carcinoma cells (PC3), as well as membranolytic capability in model cell membrane, were studied. The phyto-functionalized Ca-MgONPs were characterized using UV-Visible spectroscopy (UV-Vis), Transmission Electron Microscopy (TEM), Energy Dispersive X-Ray Spectroscopy (EDX), X-ray Diffraction (XRD), Fourier Transform Infra-Red Spectroscopy (FT-IR) and Atomic Force Microscopy (AFM). Observation of characteristic peaks by spectroscopic and microscopic analysis confirmed the synthesis of Ca-MgONPs. The Ca-MgONPs showed broad spectrum of bactericidal activity against both gram-positive and gram-negative bacteria and fungicidal activity against two species of the Candida fungus. The Ca-MgONPs also exhibited dose-dependent and selective inhibition of proliferating PC3 cells with IC of 123.65 ± 4.82 μg/mL at 24 h, however, without having any cytotoxicity toward non-cancerous HEK293 cells. Further studies aimed at understanding the probable mechanism of toxicity of Ca-MgONPs in PC3 cells, the results indicated a significant reduction in cell migration capacities, increment in cytosolic ROS, loss of mitochondrial transmembrane potential, DNA damage and S-phase cell cycle arrest. Ca-MgONPs also induced pore formation in a synthetic large unilamellar vesicle. Thus, Ca-MgONPs might be useful in the effective management of several human pathogens of concern and some more cancer types.

摘要

化学合成纳米粒子和粗提植物提取物作为抗菌-抗癌药物有许多局限性。在本研究中,我们使用具有相对较少但巨大药用特性的积雪草提取物 (CaE) 作为还原剂和稳定剂,使用硝酸镁来绿色合成氧化镁纳米粒子 (MgONPs)。与块状材料相比,研究了 Ca-MgONPs 作为一种改进的抗菌、抗真菌和抗人类前列腺癌细胞 (PC3) 癌药物的能力,以及在模型细胞膜中的溶血能力。使用紫外可见光谱 (UV-Vis)、透射电子显微镜 (TEM)、能量色散 X 射线光谱 (EDX)、X 射线衍射 (XRD)、傅里叶变换红外光谱 (FT-IR) 和原子力显微镜 (AFM) 对植物功能化的 Ca-MgONPs 进行了表征。光谱和显微镜分析观察到特征峰,证实了 Ca-MgONPs 的合成。Ca-MgONPs 对革兰氏阳性和革兰氏阴性细菌表现出广谱杀菌活性,对两种念珠菌真菌表现出杀菌活性。Ca-MgONPs 还表现出剂量依赖性和对增殖的 PC3 细胞的选择性抑制作用,在 24 小时时 IC 为 123.65±4.82μg/mL,而对非癌细胞 HEK293 细胞没有任何细胞毒性。为了进一步研究 Ca-MgONPs 在 PC3 细胞中的毒性的可能机制,结果表明细胞迁移能力显著降低,细胞内 ROS 增加,线粒体跨膜电位丧失,DNA 损伤和 S 期细胞周期停滞。Ca-MgONPs 还在合成的大单室囊泡中诱导孔形成。因此,Ca-MgONPs 可能有助于有效管理几种受关注的人类病原体和一些更多类型的癌症。

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