Our main focus was to evaluate the efficacy of silver and sodium dichloroacetate as dual-function agents to be used in melanoma treatment. This strategy is designed to increase the activity of these two compounds that affect DNA integrity and the mitochondria at different levels. Furthermore, we evaluated if the cell death mechanism induced by our treatments was immunogenic cell death. To evaluate antitumor efficacy, we assessed tumor volume and production of tumor necrosis factor-α, nuclear factor κ B (both by ELISA), and nitric oxide levels (Nitrate/Nitrite colorimetric assay kit); for immunogenic cell death, we evaluated the release of danger-associated molecular patterns using immunohistochemistry and flow cytometry, as well as an in vivo challenge. Our results showed that the combination of colloidal silver and sodium dichloroacetate is more effective than each treatment alone and that the antitumor mechanism is not through immunogenic cell death. Furthermore, this study can broadly contribute to the development of dichloroacetate-loaded silver nanoparticles and to the design targeted pharmacological formulations to fight melanoma as well as other types of cancer.

中文翻译：

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银和二氯乙酸钠联合抗黑素瘤的体内抗肿瘤和免疫原性评价

我们的主要重点是评估银和二氯乙酸钠作为用于黑色素瘤治疗的双重功能药物的功效。设计此策略旨在提高这两种化合物的活性，这些化合物以不同的水平影响DNA完整性和线粒体。此外，我们评估了由我们的治疗诱导的细胞死亡机制是否是免疫原性细胞死亡。为了评估抗肿瘤功效，我们评估了肿瘤体积和肿瘤坏死因子-α，核因子κB（均通过ELISA）和一氧化氮水平（硝酸盐/亚硝酸盐比色测定试剂盒）的产生；对于免疫原性细胞死亡，我们使用免疫组织化学和流式细胞术以及在体内评估了危险相关分子模式的释放挑战。我们的结果表明，胶体银和二氯乙酸钠的组合比单独的每种治疗更有效，并且抗肿瘤机制不是通过免疫原性细胞死亡。此外，这项研究可以广泛地促进载有二氯乙酸盐的银纳米颗粒的开发，并有助于设计针对性的药理制剂以对抗黑素瘤以及其他类型的癌症。