External stimuli triggering chemical reactions in cancer cells to generate highly reactive chemical species are very appealing for cancer therapy, in which external irradiation activating sensitizers to transfer energy or electrons to surrounding oxygen or other molecules is critical for generating cytotoxic reactive species. However, poor light penetration into tissue, low activity of sensitizers, and reliance on oxygen supply restrict the generation of cytotoxic chemical species in hypoxic tumors, which lowers the therapeutic efficacy. Here, this work presents galvanic cell nanomaterials that can directly release highly reactive electrons in tumors without external irradiation or photosensitizers. The released reactive electrons directly react with surrounding biomolecules such as proteins and DNA within tumors to destroy them or react with other surrounding (bio)molecules to yield cytotoxic chemical species to eliminate tumors independent of oxygen. Administering these nanogalvanic cells to mice results in almost complete remission of subcutaneous solid tumors and deep metastatic tumors. The results demonstrate that this strategy can further arouse an immune response even in a hypoxic environment. This method offers a promising approach to effectively eliminate tumors, similar to photodynamic therapy, but does not require oxygen or irradiation to activate photosensitizers.

中文翻译：

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纳米原电池在肿瘤中释放高活性电子，有效消除肿瘤


外部刺激触发癌细胞中的化学反应以产生高活性化学物质对于癌症治疗非常有吸引力，其中外部辐射激活敏化剂以将能量或电子转移到周围的氧或其他分子对于产生细胞毒性反应物质至关重要。然而，光对组织的穿透性差、敏化剂活性低以及对氧气供应的依赖限制了缺氧肿瘤中细胞毒性化学物质的产生，从而降低了治疗效果。在这里，这项工作提出了原电池纳米材料，可以直接在肿瘤中释放高活性电子，无需外部照射或光敏剂。释放的活性电子直接与周围的生物分子（例如肿瘤内的蛋白质和DNA）反应以破坏它们，或与其他周围的（生物）分子反应产生细胞毒性化学物质，从而无需氧气即可消除肿瘤。将这些纳米原电池给予小鼠，皮下实体瘤和深部转移瘤几乎完全缓解。结果表明，即使在缺氧环境中，这种策略也可以进一步激发免疫反应。这种方法提供了一种有效消除肿瘤的有前途的方法，类似于光动力疗法，但不需要氧气或辐射来激活光敏剂。