Nanostructure-based functions are omnipresent in nature and essential for the diversity of life. Unlike small molecules, which are often inhibitors of enzymes or biomimetics with established methods of elucidation, we show that functions of nanoscale structures in cells are complex and can implicate system-level effects such as the regulation of energy and redox homeostasis. Herein, we design a platinum(II)-containing tripeptide that assembles into intracellular fibrillar nanostructures upon molecular rearrangement in the presence of endogenous H₂O₂. The formed nanostructures blocked metabolic functions, including aerobic glycolysis and oxidative phosphorylation, thereby shutting down ATP production. As a consequence, ATP-dependent actin formation and glucose metabolite-dependent histone deacetylase activity are downregulated. We demonstrate that assembly-driven nanomaterials offer a rich avenue to achieve broad-spectrum bioactivities that could provide new opportunities in drug discovery.

中文翻译：

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铂 (II)-金属肽纳米结构的原位组装破坏能量稳态和细胞代谢

基于纳米结构的功能在自然界中无处不在，对生命的多样性至关重要。与小分子不同，小分子通常是酶的抑制剂或具有已建立的阐明方法的仿生学，我们表明细胞中纳米级结构的功能是复杂的，并且可能涉及系统级效应，例如能量调节和氧化还原稳态。_{在此，我们设计了一种含铂 (II) 的三肽，在内源性 H 2} O ₂存在下通过分子重排组装成细胞内纤维状纳米结构. 形成的纳米结构阻断了代谢功能，包括有氧糖酵解和氧化磷酸化，从而关闭了 ATP 的产生。因此，ATP 依赖性肌动蛋白形成和葡萄糖代谢物依赖性组蛋白脱乙酰酶活性被下调。我们证明，组装驱动的纳米材料为实现广谱生物活性提供了丰富的途径，可以为药物发现提供新的机会。