BACKGROUND Synthesis of nanoparticles (NPs) and their incorporation in materials are amongst the most studied topics in chemistry, physics and material science. Gold NPs have applications in medicine due to their antibacterial and anticancer activities, in biomedical imaging and diagnostic test. Despite chemical synthesis of NPs are well characterized and controlled, they rely on the utilization of harsh chemical conditions and organic solvent and generate toxic residues. Therefore, greener and more sustainable alternative methods for NPs synthesis have been developed recently. These methods use microorganisms, mainly yeast or yeast cell extract. NPs synthesis with culture supernatants are most of the time the preferred method since it facilitates the purification scheme for the recovery of the NPs. Extraction of NPs, formed within the cells or cell-wall, is laborious, time-consuming and are not cost effective. The bioactivities of NPs, namely antimicrobial and anticancer, are known to be related to NPs shape, size and size distribution. RESULTS Herein, we reported on the green synthesis of gold nanoparticles (AuNPs) mediated by pyomelanin purified from the yeast Yarrowia lipolytica. A three levels four factorial Box-Behnken Design (BBD) was used to evaluate the influence of temperature, pH, gold salt and pyomelanin concentration on the nanoparticle size distribution. Based on the BBD, a quadratic model was established and was applied to predict the experimental parameters that yield to AuNPs with specific size. The synthesized nanoparticles with median size value of 104 nm were of nanocrystalline structure, mostly polygonal or spherical. They exhibited a high colloidal stability with zeta potential of - 28.96 mV and a moderate polydispersity index of 0.267. The absence of cytotoxicity of the AuNPs was investigated on two mammalian cell lines, namely mouse fibroblasts (NIH3T3) and human osteosarcoma cells (U2OS). Cell viability was only reduced at AuNPs concentration higher than 160 µg/mL. Moreover, they did not affect on the cell morphology. CONCLUSION Our results indicate that different process parameters affect significantly nanoparticles size however with the mathematical model it is possible to define the size of AuNPs. Moreover, this melanin-based gold nanoparticles showed neither cytotoxicity effect nor altered cell morphology.

中文翻译：

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绿色油菜素介导的金纳米粒子合成：建模和设计，理化和生物学特性。

背景技术纳米颗粒（NPs）的合成及其在材料中的结合是化学，物理和材料科学中研究最多的主题之一。金纳米颗粒由于其抗菌和抗癌活性而在医学，生物医学成像和诊​​断测试中得到了应用。尽管NP的化学合成得到了很好的表征和控制，但它们仍依赖于苛刻的化学条件和有机溶剂的利用并产生有毒残留物。因此，近来已经开发了用于NP合成的更绿色和更可持续的替代方法。这些方法使用微生物，主要是酵母或酵母细胞提取物。用培养上清液进行NP合成在大多数情况下是首选方法，因为它有助于回收NP的纯化方案。NP的提取 在细胞或细胞壁内形成的细胞是费力的，费时的并且不是成本有效的。已知NP的生物活性，即抗微生物剂和抗癌剂，与NP的形状，大小和大小分布有关。结果在本文中，我们报道了从解脂耶氏酵母中纯化的吡喃丙氨酸介导的金纳米颗粒（AuNPs）的绿色合成。使用三级四因子Box-Behnken设计（BBD）来评估温度，pH，金盐和pyomelanin浓度对纳米粒度分布的影响。基于BBD，建立了二次模型，并将其用于预测产生具有特定大小的AuNPs的实验参数。合成的中值粒径为104 nm的纳米颗粒具有纳米晶体结构，大部分为多边形或球形。它们表现出高的胶体稳定性，ζ电位为-28.96 mV，中等多分散指数为0.267。在两种哺乳动物细胞系，即小鼠成纤维细胞（NIH3T3）和人骨肉瘤细胞（U2OS）上研究了AuNPs无细胞毒性。仅当AuNPs浓度高于160 µg / mL时，细胞活力才降低。而且，它们不影响细胞形态。结论我们的结果表明，不同的工艺参数会显着影响纳米粒子的尺寸，但是通过数学模型，可以定义AuNPs的尺寸。而且，这种基于黑色素的金纳米颗粒既没有显示出细胞毒性作用，也没有显示出改变的细胞形态。在两种哺乳动物细胞系，即小鼠成纤维细胞（NIH3T3）和人骨肉瘤细胞（U2OS）上研究了AuNPs无细胞毒性。仅当AuNPs浓度高于160 µg / mL时，细胞活力才降低。而且，它们不影响细胞形态。结论我们的结果表明，不同的工艺参数会显着影响纳米粒子的尺寸，但是通过数学模型，可以定义AuNPs的尺寸。而且，这种基于黑色素的金纳米颗粒既没有显示出细胞毒性作用，也没有显示出改变的细胞形态。在两种哺乳动物细胞系，即小鼠成纤维细胞（NIH3T3）和人骨肉瘤细胞（U2OS）上研究了AuNPs无细胞毒性。仅当AuNPs浓度高于160 µg / mL时，细胞活力才降低。而且，它们不影响细胞形态。结论我们的结果表明，不同的工艺参数会显着影响纳米粒子的尺寸，但是通过数学模型，可以定义AuNPs的尺寸。而且，这种基于黑色素的金纳米颗粒既没有显示出细胞毒性作用，也没有显示出改变的细胞形态。结论我们的结果表明，不同的工艺参数会显着影响纳米粒子的尺寸，但是通过数学模型，可以定义AuNPs的尺寸。而且，这种基于黑色素的金纳米颗粒既没有显示出细胞毒性作用，也没有显示出改变的细胞形态。结论我们的结果表明，不同的工艺参数会显着影响纳米粒子的尺寸，但是通过数学模型，可以定义AuNPs的尺寸。而且，这种基于黑色素的金纳米颗粒既没有显示出细胞毒性作用，也没有显示出改变的细胞形态。