Breast cancer is therapeutically very challenging to treat as it has the main four known genetic alterations, which result in the existence of several phenotypes leading to the difference in the mode of therapy and with poor outcome. Metallic nanoparticles of silver or copper have been studied previously as anticancer agents in breast cancer and other types of cancers. However, the anticancer effect of silver–copper alloy nanoparticles (AgCu-NP) is not studied in breast cancer. In this study, we aim to synthesize silver nanoparticles (Ag-NP), or copper nanoparticles (Cu-NP), and AgCu-NP and evaluate their toxicity in breast cancer and healthy breast cells. We synthesized sodium citrate and mercapto-propionic acid (MPA-3) capped water-soluble metallic nanoparticles of Ag-NP or Cu-NP and an alloy of three different combinations of AgCu-NP. High-resolution transmission electron microscopy characterization of nanoparticles revealed the spherical shape nanoparticles of varied sizes, furthermore dynamic light scattering characterization was performed, which investigated the hydrodynamic size and stability in phosphate buffer solution. Energy-dispersive X-ray spectroscopy (EDS) measurements were obtained from the transmission electron microscope to study the composition of alloy nanoparticles and the distribution pattern of silver and copper in the alloy nanoparticles. We measured the toxicity of nanoparticles to breast cancer MCF-7 cell line by MTT assay and compared the toxic effect with non-cancerous breast epithelial cells MCF-10A. Our data showed that Ag-NP or Cu-NP have no effect on cancer cells or healthy cells, except Ag-NP at 20 µg/ml were toxic to cancer cells. However, AgCu-NP were significantly toxic to MCF-7 cells at 10 µg/ml concentration, while as AgCu-NP have no toxic effect on healthy cells. Furthermore, we observed the cell death pathway by the apoptosis marker Annexin-V which showed non-significant results, while the exposure of AgCu-NP in MCF-7 cells leads to toxicity and also caused significant increase in MMP-9 level, which suggests the cell death may be associated with other pathways such as autophagy and oxidative stress related. The data suggest that the AgCu-NP alloy imposes preferential toxicity in breast cancer MCF-7 cells and thus could be exploited as a new candidate for further anticancer investigation

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不同比例的银铜合金纳米颗粒的合成与分析显示乳腺癌细胞具有抗癌活性

乳腺癌在治疗上具有很大的挑战性，因为它具有四个已知的主要遗传改变，导致几种表型的存在，导致治疗方式的差异，并且结果差。先前已经研究了银或铜的金属纳米颗粒作为乳腺癌和其他类型癌症的抗癌剂。然而，尚未在乳腺癌中研究银铜合金纳米颗粒（AgCu-NP）的抗癌作用。在这项研究中，我们旨在合成银纳米颗粒（Ag-NP）或铜纳米颗粒（Cu-NP）和AgCu-NP，并评估它们在乳腺癌和健康乳腺细胞中的毒性。我们合成了柠檬酸钠和巯基丙酸（MPA-3）封端的Ag-NP或Cu-NP水溶性金属纳米颗粒，以及三种不同AgCu-NP组合的合金。纳米粒子的高分辨率透射电子显微镜表征揭示了各种尺寸的球形纳米粒子，此外还进行了动态光散射表征，其研究了磷酸盐缓冲溶液中的流体动力学尺寸和稳定性。从透射电子显微镜获得能量色散X射线光谱（EDS）测量，以研究合金纳米颗粒的组成以及银和铜在合金纳米颗粒中的分布方式。我们通过MTT测定法测量了纳米粒子对乳腺癌MCF-7细胞系的毒性，并将其与非癌性乳腺癌上皮细胞MCF-10A的毒性作用进行了比较。我们的数据表明，Ag-NP或Cu-NP对癌细胞或健康细胞没有影响，除了20 µg / ml的Ag-NP对癌细胞有毒性。然而，AgCu-NP在10 µg / ml的浓度下对MCF-7细胞有明显的毒性，而AgCu-NP对健康细胞没有毒性。此外，我们观察到凋亡标记物Annexin-V的细胞死亡途径显示出无意义的结果，而MCF-7细胞中AgCu-NP的暴露会导致毒性并且还导致MMP-9水平的显着增加，这表明细胞死亡可能与其他途径如自噬和氧化应激有关。数据表明，AgCu-NP合金对乳腺癌MCF-7细胞具有优先毒性，因此可作为进一步抗癌研究的新候选物 我们通过凋亡标记膜Annexin-V观察到了细胞死亡途径，该结果显示了不重要的结果，而AgCu-NP在MCF-7细胞中的暴露会导致毒性并且还导致MMP-9水平的显着增加，这提示该细胞死亡可能与其他途径如自噬和氧化应激有关。数据表明，AgCu-NP合金对乳腺癌MCF-7细胞具有优先毒性，因此可作为进一步抗癌研究的新候选物 我们通过凋亡标记膜Annexin-V观察到了细胞死亡途径，该结果显示了不重要的结果，而AgCu-NP在MCF-7细胞中的暴露会导致毒性并且还导致MMP-9水平的显着增加，这提示该细胞死亡可能与其他途径如自噬和氧化应激有关。数据表明，AgCu-NP合金对乳腺癌MCF-7细胞具有优先毒性，因此可作为进一步抗癌研究的新候选物