Catalytic cancer therapy targets cancer cells by exploiting the specific characteristics of the tumor microenvironment (TME). TME-based catalytic strategies rely on the use of molecules already present in the TME. Amino groups seem to be a suitable target, given the abundance of proteins and peptides in biological environments. Here we show that catalytic CuFe₂O₄ nanoparticles are able to foster transaminations with different amino acids and pyruvate, another key molecule present in the TME. We observed a significant in cellulo decrease in glutamine and alanine levels up to 48 h after treatment. In addition, we found that di- and tripeptides also undergo catalytic transamination, thereby extending the range of the effects to other molecules such as glutathione disulfide (GSSG). Mechanistic calculations for GSSG transamination revealed the formation of an imine between the oxo group of pyruvate and the free −NH₂ group of GSSG. Our results highlight transamination as alternative to the existing toolbox of catalytic therapies.

中文翻译：

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肿瘤微环境条件下纳米颗粒催化的氨基转移：破坏癌细胞中氨基酸和 GSSG 库的新工具

催化癌症疗法通过利用肿瘤微环境（TME）的特定特征来靶向癌细胞。基于 TME 的催化策略依赖于 TME 中已有分子的使用。鉴于生物环境中蛋白质和肽的丰富性，氨基似乎是一个合适的目标。在这里，我们证明催化 CuFe ₂ O ₄纳米颗粒能够促进不同氨基酸和丙酮酸（TME 中存在的另一个关键分子）的转氨作用。我们观察到治疗后 48 小时内谷氨酰胺和丙氨酸水平显着下降。此外，我们发现二肽和三肽也会发生催化氨基转移，从而将影响范围扩展到其他分子，例如二硫化谷胱甘肽（GSSG）。 GSSG转氨作用的机理计算揭示了丙酮酸的氧代基团和GSSG的游离-NH ₂基团之间形成亚胺。我们的结果强调转氨作用可以替代现有的催化疗法工具箱。