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用于增强癌症治疗的生物相容的银、金和金银合金纳米粒子:体外和体内研究进展。

Biocompatible silver, gold and silver/gold alloy nanoparticles for enhanced cancer therapy: in vitro and in vivo perspectives.

机构信息

Actinobacterial Research Laboratory, Department of Microbiology, Periyar University, Periyar Palkalai Nagar, Salem 636 011, Tamil Nadu, India.

出版信息

Nanoscale. 2017 Nov 9;9(43):16773-16790. doi: 10.1039/c7nr04979j.

Abstract

The aims of nano oncology are to detect, target and treat cancer cells without any side effects. The present study describes the microbial synthesis of biocompatible nanoparticles of silver (AgNPs), gold (AuNPs) and their alloy (Ag/AuNPs) for hepatoprotective activity against diethylnitrosamine (DEN)-induced liver cancer in a Sprague Dawley (SD) rat model. The crystalline nature and physicochemical features of the nanoparticles were identified by Fourier transform infra-red (FT-IR) spectroscopy, X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), transmission electron microscopy (TEM) and selected area electron diffraction (SAED) analysis. Based on the instrumental analysis, the synthesised nanomaterials were found to be spherical in shape and have an average size in the nano region. Nitrate reductase was characterized after partial purification of the culture filtrate via polyacrylamide gel electrophoresis and its molecular weight was determined as ∼45 kDa. Furthermore, the IC values of the AgNPs, AuNPs and Ag/AuNPs on HepG2 cells were determined as 38.42 μg ml, 43.25 μg ml and 39.20 μg ml, respectively, and the antioxidant potential of the nanoparticles was also systematically analyzed. The No-Observed-Adverse-Effect-Level (NOAEL) for the AgNPs was determined to be 2000 mg per kg of body weight (bw) from an acute toxicity test. Similarly, the NOAEL of AuNPs and Ag/AuNPs were calculated as 1000 mg per kg bw. Based on the in vivo studies, a significant tumour reduction (∼45 to 65%) was observed in the nanoparticle-treated animals, which was further confirmed by hematological, biochemical, TEM and histopathological analysis. Immunohistochemistry analysis confirmed the presence of BAX antibodies, up to immunoreactive (3+) level in treated animals. These results strongly suggest the potential anticancer activities of AgNPs, AuNPs and Ag/AuNPs against DEN-induced liver cancer and they could be potential candidates for effective nano drug development.

摘要

纳米肿瘤学的目标是在没有任何副作用的情况下检测、靶向和治疗癌细胞。本研究描述了微生物合成的银(AgNPs)、金(AuNPs)及其合金(Ag/AuNPs)纳米粒子的生物相容性,用于在 Sprague Dawley(SD)大鼠模型中对抗二乙基亚硝胺(DEN)诱导的肝癌的肝保护活性。通过傅里叶变换红外(FT-IR)光谱、X 射线衍射(XRD)、X 射线光电子能谱(XPS)、透射电子显微镜(TEM)和选区电子衍射(SAED)分析确定了纳米粒子的晶体性质和物理化学特性。基于仪器分析,发现合成的纳米材料为球形,具有纳米区域的平均尺寸。通过聚丙烯酰胺凝胶电泳对培养滤液进行部分纯化后,对硝酸盐还原酶进行了表征,并确定其分子量约为 45 kDa。此外,还分别测定了 AgNPs、AuNPs 和 Ag/AuNPs 对 HepG2 细胞的 IC 值,分别为 38.42 μg ml、43.25 μg ml 和 39.20 μg ml,还系统分析了纳米粒子的抗氧化潜力。急性毒性试验确定 AgNPs 的无观察不良效应水平(NOAEL)为 2000 mg/kg 体重(bw)。同样,AuNPs 和 Ag/AuNPs 的 NOAEL 计算为 1000 mg/kg bw。基于体内研究,在纳米粒子处理的动物中观察到肿瘤显著减少(约 45%至 65%),这在血液学、生物化学、TEM 和组织病理学分析中得到了进一步证实。免疫组织化学分析证实,在处理动物中存在 BAX 抗体,达到免疫反应性(3+)水平。这些结果强烈表明 AgNPs、AuNPs 和 Ag/AuNPs 对 DEN 诱导的肝癌具有潜在的抗癌活性,它们可能是有效纳米药物开发的潜在候选药物。

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