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Cellular toxicology and mechanism of the response to silver-based nanoparticle exposure in Ewing's sarcoma cells

机译：eWINGS肉瘤细胞中银基纳米粒子暴露的响应细胞毒理学及机理

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Ewing's sarcoma is the most aggressive connective tissue tumor, mainly affecting children and adolescents; the 5 year survival rate is only 50%. Current treatments have poor effectiveness, and more efficient treatments are being sought. Silver-based nanoparticles, such as silver chloride nanoparticles (AgCl-NPs) and silver/silver chloride (Ag/AgCl-NPs) nanoparticles, can be biologically produced and can release Ag+ ions into solution; however, their antitumor activity has been minimally investigated. The aim of this study was to evaluate the antitumor potential of AgCl-NPs and Ag/AgCl-NPs against Ewing's sarcoma cells. A673 cells (Ewing's sarcoma) were treated for 72 h with 0-12.5 mu g ml(-1) of Ag/AgCl-NPs or 0-40 mu g ml(-1) of AgCl-NPs. Human cells from the RPE-1 cell line (pigmented retinal epithelium) were used as a model of nontumor cells. The RPE-1 cells were less affected by the administration of AgCl-NPs or Ag/AgCl-NPs, with small reductions in the number of cells and viability and a small increase in apoptosis rates, while lysosomal damage, changes in reactive oxygen species (ROS) production, loss of mitochondrial membrane potential and alterations in microfilaments or cell areas were not observed. A673 tumor cells had significantly reduced number and viability levels when treated with AgCl-NPs, with reductions of 65.05% and 99.17%, respectively, whereas with Ag/AgCl-NP treatment, reductions of 65.53% and 92.51% were observed, respectively. When treated with silver-based nanoparticles, A673 cells also showed a significant increase in ROS production and loss of mitochondrial membrane potential, which culminated in an increase in the percentage of apoptosis among the population. Lysosomal damage was also observed when A673 cells were treated with the highest concentration of AgCl-NPs. In conclusion, the results showed that both AgCl-NPs and Ag/AgCl-NPs had some antitumor activity with minimal effects against healthy cells, which demonstrated the possibility of their use in cancer therapy.
机译：尤因肉瘤是最具侵袭性的结缔组织肿瘤，主要影响儿童和青少年；5年生存率仅为50%。目前的治疗效果不佳，人们正在寻求更有效的治疗方法。银基纳米颗粒，例如氯化银纳米颗粒（AgCl NP）和银/氯化银纳米颗粒（Ag/AgCl NP），可以通过生物方法制备，并可以将Ag+离子释放到溶液中；然而，对其抗肿瘤活性的研究很少。本研究的目的是评估AgCl纳米粒和Ag/AgCl纳米粒对尤因肉瘤细胞的抗肿瘤潜力。A673细胞（尤因肉瘤）用0-12.5μg ml（-1）Ag/AgCl NP或0-40μg ml（-1）AgCl NP处理72小时。来自RPE-1细胞系（色素视网膜上皮）的人类细胞被用作非肿瘤细胞的模型。施用AgCl NP或Ag/AgCl NP对RPE-1细胞的影响较小，细胞数量和存活率略有减少，凋亡率略有增加，而未观察到溶酶体损伤、活性氧（ROS）产生的变化、线粒体膜电位的丧失以及微丝或细胞区域的改变。当使用AgCl NP治疗时，A673肿瘤细胞的数量和存活水平显著减少，分别减少65.05%和99.17%，而使用Ag/AgCl NP治疗时，分别减少65.53%和92.51%。当用银基纳米颗粒处理时，A673细胞也表现出活性氧生成的显著增加和线粒体膜电位的丧失，最终导致细胞凋亡的百分比增加。当A673细胞被最高浓度的AgCl NP处理时，也观察到溶酶体损伤。总之，结果表明AgCl-NP和Ag/AgCl-NP都具有一定的抗肿瘤活性，对健康细胞的影响最小，这表明它们在癌症治疗中的应用是可能的。

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