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首页> 外文期刊>ACS Omega >Biosynthesized Protein-Capped Silver Nanoparticles Induce ROS-Dependent Proapoptotic Signals and Prosurvival Autophagy in Cancer Cells
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Biosynthesized Protein-Capped Silver Nanoparticles Induce ROS-Dependent Proapoptotic Signals and Prosurvival Autophagy in Cancer Cells

机译：生物合成的蛋白质封端的银纳米颗粒在癌细胞中诱导ROS依赖的凋亡信号和生存自噬。

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In recent years, the use of silver nanoparticles (AgNPs) in biomedical applications has shown an unprecedented boost along with simultaneous expansion of rapid, high-yielding, and sustainable AgNP synthesis methods that can deliver particles with well-defined characteristics. The present study demonstrates the potential of metal-tolerant soil fungal isolate Penicillium shearii AJP05 for the synthesis of protein-capped AgNPs. The particles were characterized using standard techniques, namely, UV–visible spectroscopy, transmission electron microscopy, X-ray diffraction, and Fourier transform infrared spectroscopy. The anticancer activity of the biosynthesized AgNPs was analyzed in two different cell types with varied origin, for example, epithelial (hepatoma) and mesenchymal (osteosarcoma). The biological NPs (bAgNPs) with fungal-derived outer protein coat were found to be more cytotoxic than bare bAgNPs or chemically synthesized AgNPs (cAgNPs). Elucidation of the molecular mechanism revealed that bAgNPs induce cytotoxicity through elevation of reactive oxygen species (ROS) levels and induction of apoptosis. Upregulation of autophagy and activation of JNK signaling were found to act as a prosurvival strategy upon bAgNP treatment, whereas ERK signaling served as a prodeath signal. Interestingly, inhibition of autophagy increased the production of ROS, resulting in enhanced cell death. Finally, bAgNPs were also found to sensitize cells with acquired resistance to cisplatin, providing valuable insights into the therapeutic potential of bAgNPs. To the best of our knowledge, this is the first study that provides a holistic idea about the molecular mechanisms behind the cytotoxic activity of protein-capped AgNPs synthesized using a metal-tolerant soil fungus.
机译：近年来，在生物医学应用中银纳米颗粒（AgNPs）的使用已显示出空前的增长，同时迅速扩展了可以提供具有明确特征的颗粒的快速，高产且可持续的AgNP合成方法。本研究证明了耐金属的土壤真菌分离株Penicillium shearii AJP05在合成蛋白封闭的AgNPs方面的潜力。使用标准技术对颗粒进行表征，即紫外可见光谱，透射电子显微镜，X射线衍射和傅立叶变换红外光谱。在具有不同来源的两种不同细胞类型中分析了生物合成的AgNP的抗癌活性，例如上皮细胞（肝癌）和间质细胞（骨肉瘤）。发现具有真菌衍生的外部蛋白被膜的生物NPs（bAgNPs）比裸bAgNPs或化学合成的AgNPs（cAgNPs）具有更高的细胞毒性。对分子机制的阐明表明，bAgNPs通过提高活性氧（ROS）水平和诱导凋亡来诱导细胞毒性。发现自噬的上调和JNK信号的激活可作为bAgNP治疗后的生存策略，而ERK信号可作为死亡信号。有趣的是，自噬的抑制增加了ROS的产生，导致细胞死亡增加。最后，还发现了bAgNP可以使细胞获得顺铂耐药性，从而为bAgNP的治疗潜力提供有价值的见解。据我们所知，这是第一个提供有关使用耐金属性土壤真菌合成的蛋白质加帽的AgNPs细胞毒活性背后的分子机制的分子机制的整体研究。

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