Chen Kerong, Zhou Anwei, Zhou Xinyuan, Liu Yuhang, Xu Yurui, Ning Xinghai
National Laboratory of Solid State Microstructures, Collaborative Innovation Center of Advanced Microstructures, Chemistry and Biomedicine Innovation Center, College of Engineering and Applied Sciences, Jiangsu Key Laboratory of Artificial Functional Materials, Nanjing University, Nanjing 210093, China.
National Laboratory of Solid State Microstructures, Collaborative Innovation Center of Advanced Microstructures, School of Physics, Nanjing University, Nanjing 210093, China.
Nano Lett. 2023 Apr 12;23(7):3038-3047. doi: 10.1021/acs.nanolett.3c00434. Epub 2023 Mar 23.
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.
由于其独特的细胞死亡机制,铜死亡的最新进展为推进声动力疗法(SDT)的治疗方法开发提供了思路。在此,我们精心研制了一种智能细胞衍生纳米机器人(SonoCu),它由巨噬细胞膜伪装的纳米载体组成,该纳米载体包裹着铜掺杂的沸石咪唑酯骨架-8(ZIF-8)、全氟碳和超声敏化剂Ce6,用于协同触发铜死亡增强的SDT。SonoCu不仅通过细胞膜伪装改善了肿瘤积累和癌细胞摄取,还能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死亡。重要的是,SDT的有效性可通过铜死亡通过多种机制进一步放大,包括活性氧积累、蛋白毒性应激和代谢调节,这些机制协同使癌细胞死亡敏感化。特别地,SonoCu对癌细胞表现出超声响应性细胞毒性,但对健康细胞无此作用,赋予其良好的生物安全性。因此,我们提出了SDT与铜死亡的首个抗癌联合疗法,这可能会激发对合理多模态治疗策略的研究。
J Control Release. 2023-2
Acta Biomater. 2021-7-15
Theranostics. 2025-7-11
J Nanobiotechnology. 2025-7-30
J Nanobiotechnology. 2025-7-28
Mediterr J Hematol Infect Dis. 2025-7-1
J Cell Mol Med. 2025-6
Front Cell Dev Biol. 2025-4-11