Esophageal cancer (EC) is the sixth leading cause of cancer deaths worldwide with a low 5 year survival rate. More effective chemotherapeutic drugs, either new or repurposing ones, are urgently needed. Disulfiram (DSF) is a safe and public domain drug for alcohol addiction treatment and later shown to have anticancer capability, especially when administrated together with copper. The present study is to test the hypothesis that developed copper–cysteamine (Cu-Cy) nanoparticles (NPs) can enhance the antitumor effect of DSF on esophageal cancer with a reduced risk of copper poisoning. Our results showed that Cu-Cy NPs could greatly facilitate DSF to inhibit cell proliferation in cultured human esophageal cancer cells. Interestingly, the combined inhibitory function could be further enhanced when DSF and Cu-Cy NPs were present at an optimal molar ratio of 1:4. The results of the change in physical color, UV–vis absorption and fluorescence spectra, X-ray diffraction patterns, and FTIR spectra from a mixture of DSF and Cu-Cy NPs suggest a possible reaction between DSF and Cu-Cy NPs and the formation of a complex. Furthermore, cellular mechanistic studies revealed that the combination of DSF and Cu-Cy NPs resulted in reactive oxygen species accumulation and blocked nuclear translocation of NF-κB (p65) in esophageal cancer cells. Moreover, in xenograft nude mice, combined administration of DSF and Cu-Cy NPs greatly inhibited tumor growth without noticeable histological toxicity, while any single agent at the same doses presented no inhibitory function. Together, this study demonstrates an effective anticancer function of combined treatment of DSF and Cu-Cy NPs in vitro and in vivo, which could be a promising chemotherapy for esophageal cancer patients.

中文翻译：

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双硫仑和铜-半胱胺纳米颗粒的组合可增强对食道癌的抗肿瘤作用

食道癌（EC）是全球癌症死亡的第六大主要原因，其5年生存率很低。迫切需要更有效的化学治疗药物，无论是新的药物还是重新使用的药物。双硫仑（DSF）是一种安全且公共领域的酒精成瘾治疗药物，后来被证明具有抗癌能力，尤其是与铜一起给药时。本研究旨在验证以下假设：已开发的铜-半胱胺（Cu-Cy）纳米颗粒（NPs）可以增强DSF对食道癌的抗肿瘤作用，并降低铜中毒的风险。我们的结果表明，Cu-Cy NPs可以极大地促进DSF抑制培养的人食道癌细胞中的细胞增殖。有趣的是 当DSF和Cu-Cy NPs的最佳摩尔比为1：4时，组合的抑制功能可以进一步增强。DSF和Cu-Cy NP混合物的物理颜色，紫外可见吸收和荧光光谱，X射线衍射图和FTIR光谱的变化结果表明，DSF和Cu-Cy NP之间可能发生反应，并且形成复杂的。此外，细胞机制研究表明，DSF和Cu-Cy NP的组合导致食管癌细胞中活性氧的积累并阻断了NF-κB（p65）的核易位。此外，在异种移植裸鼠中，DSF和Cu-Cy NP的联合给药可在没有明显组织学毒性的情况下极大地抑制肿瘤的生长，而相同剂量的任何单一药物均无抑制作用。一起，