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

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 nanocarri...

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Bibliographic Details
Published in:Nano letters 2023-04, Vol.23 (7), p.3038-3047
Main Authors: Chen, Kerong, Zhou, Anwei, Zhou, Xinyuan, Liu, Yuhang, Xu, Yurui, Ning, Xinghai
Format: Article
Language:English
Subjects:
Apoptosis
Cell Death
Copper
Humans
Neoplasms - therapy
Reactive Oxygen Species - metabolism
Ultrasonic Therapy
Ultrasonography
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Summary: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.
ISSN:1530-6984
1530-6992
DOI:10.1021/acs.nanolett.3c00434