Arsenical drugs have achieved hallmark success in treating patients with acute promyelocytic leukemia, but expanding their clinical utility to solid tumors has proven difficult with the contradiction between the therapeutic efficacy and the systemic toxicity. Here, leveraging efforts from materials science, biocompatible PEGylated arsenene nanodots (AsNDs@PEG) with high monoelemental arsenic purity that can selectively and effectively treat solid tumors are synthesized. The intrinsic selective killing effect of AsNDs@PEG is closely related to high oxidative stress in tumor cells, which leads to an activated valence-change of arsenic (from less toxic As⁰ to severely toxic oxidation states), followed by decreased superoxide dismutase activity and massive reactive oxygen species (ROS) production. These effects occur selectively within cancer cells, causing mitochondrial damage, cell-cycle arrest, and DNA damage. Moreover, AsNDs@PEG when applied in a multi-drug combination strategy with β-elemene, a plant-derived anticancer drug, achieves synergistic antitumor outcomes, and its newly discovered on-demand photothermal properties facilitate the elimination of the tumors without recurrence, potentially further expanding its clinical utility. In line of the practicability for a large-scale fabrication and negligible systemic toxicity of AsNDs@PEG (even at high doses and with repetitive administration), a new-concept arsenical drug with high therapeutic efficacy for selective solid tumor therapy is provided.

中文翻译：

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具有选择性杀伤作用的砷烯纳米点及其与 ß-元素的低剂量组合用于癌症治疗

砷类药物在治疗急性早幼粒细胞白血病患者方面取得了标志性的成功，但由于治疗效果和全身毒性之间的矛盾，将其临床应用扩展到实体瘤已被证明是困难的。在这里，利用材料科学的努力，合成了具有高单元素砷纯度的生物相容性聚乙二醇化砷纳米点 (AsNDs@PEG)，可以选择性地和有效地治疗实体瘤。AsNDs@PEG 的内在选择性杀伤作用与肿瘤细胞中的高氧化应激密切相关，这导致砷的价态变化（从毒性较小的 As ⁰到严重有毒的氧化态），然后是超氧化物歧化酶活性降低和大量活性氧（ROS）产生。这些效应选择性地发生在癌细胞内，导致线粒体损伤、细胞周期停滞和 DNA 损伤。此外，AsNDs@PEG 在与植物源性抗癌药物 β-榄香烯的多药组合策略中应用时，可实现协同抗肿瘤效果，其新发现的按需光热特性有助于消除肿瘤而不会复发，可能进一步扩大其临床应用。根据 AsNDs@PEG 的大规模制造和可忽略的全身毒性（即使在高剂量和重复给药下）的实用性，