An Intelligent Cell-Derived Nanorobot Bridges Synergistic Crosstalk Between Sonodynamic Therapy and Cuproptosis to Promote Cancer Treatment,Nano Letters

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An Intelligent Cell-Derived Nanorobot Bridges Synergistic Crosstalk Between Sonodynamic Therapy and Cuproptosis to Promote Cancer Treatment
Nano Letters ( IF 9.6 ) Pub Date : 2023-03-23 , DOI: 10.1021/acs.nanolett.3c00434
Kerong Chen ₁ , Anwei Zhou ₂ , Xinyuan Zhou ₁ , Yuhang Liu ₁ , Yurui Xu ₁ , Xinghai Ning ₁

Affiliation

Recent progress in cuproptosis sheds light on the development of treatment approaches for advancing sonodynamic therapy (SDT) due to its unique cell death mechanism. Herein, we elaborately developed an intelligent cell-derived nanorobot (SonoCu), composed of macrophage-membrane-camouflaged nanocarrier encapsulating copper-doped zeolitic imidazolate framework-8 (ZIF-8), perfluorocarbon, and sonosensitizer Ce6, for synergistically triggering cuproptosis-augmented SDT. SonoCu not only improved tumor accumulation and cancer-cell uptake through cell-membrane camouflaging but responded to ultrasound stimuli to enhance intratumor blood flow and oxygen supply, which consequently overcame treatment barriers and activated sonodynamic cuproptosis. Importantly, the SDT effectiveness could be further amplified by cuproptosis through multiple mechanisms, including reactive oxygen species accumulation, proteotoxic stress, and metabolic regulation, which synergistically sensitized cancer cell death. Particularly, SonoCu exhibited ultrasound-responsive cytotoxicity against cancer cells but not healthy cells, endowing it with good biosafety. Therefore, we present the first anticancer combination of SDT and cuproptosis, which may inspire studies pursuing a rational multimodal treatment strategy.

中文翻译：

一种智能细胞衍生的纳米机器人桥接声动力疗法和铜proptosis之间的协同串扰以促进癌症治疗

由于其独特的细胞死亡机制，铜细胞凋亡的最新进展揭示了推进声动力疗法 (SDT) 的治疗方法的发展。在此，我们精心开发了一种智能细胞衍生纳米机器人 (SonoCu)，由巨噬细胞膜伪装纳米载体包裹铜掺杂沸石咪唑酯骨架 8 (ZIF-8)、全氟化碳和声敏剂 Ce6 组成，用于协同触发铜凋亡增强SDT。SonoCu 不仅通过细胞膜伪装改善肿瘤积聚和癌细胞摄取，而且响应超声刺激以增强肿瘤内血流和氧气供应，从而克服治疗障碍并激活声动力铜细胞凋亡。重要的是，SDT 的有效性可以通过多种机制通过铜下垂进一步放大，包括活性氧积累、蛋白毒性应激和代谢调节，它们协同地使癌细胞死亡敏感。特别是，SonoCu 表现出对癌细胞而非健康细胞的超声响应细胞毒性，使其具有良好的生物安全性。因此，我们提出了第一个 SDT 和铜下垂的抗癌组合，这可能会激发寻求合理的多模式治疗策略的研究。

更新日期：2023-03-23

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