Journal
NATURE NANOTECHNOLOGY
Volume 14, Issue 4, Pages 379-+Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/s41565-019-0373-6
Keywords
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Funding
- National Natural Science Foundation of China (NSFC) [21327806, 21621003, 21235004, 31630027, 31430031, 31600808, 31225009]
- NSFC-German Research Foundation (DFG) [31761133013]
- 'Strategic Priority Research Program' from the Chinese Academy of Sciences [XDA09030301]
- BL14W1 station of the Shanghai Synchrotron Radiation Facility
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Mitochondrial redox homeostasis, the balance between reactive oxygen species and antioxidants such as glutathione, plays critical roles in many biological processes, including biosynthesis and apoptosis, and thus is a potential target for cancer treatment. Here, we report a mitochondrial oxidative stress amplifier, MitoCAT-g, which consists of carbon-dot-supported atomically dispersed gold (CAT-g) with further surface modifications of triphenylphosphine and cinnamaldehyde. We find that the MitoCAT-g particles specifically target mitochondria and deplete mitochondrial glutathione with atomic economy, thus amplifying the reactive oxygen species damage caused by cinnamaldehyde and finally leading to apoptosis in cancer cells. We show that imaging-guided interventional injection of these particles potently inhibits tumour growth in subcutaneous and orthotopic patient-derived xenograft hepatocellular carcinoma models without adverse effects. Our study demonstrates that MitoCAT-g amplifies the oxidative stress in mitochondria and suppresses tumour growth in vivo, representing a promising agent for anticancer applications.
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