Journal
SMALL
Volume 16, Issue 33, Pages -Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/smll.202001251
Keywords
ferroptosis; lipid peroxides; metal organic frameworks; photothermal therapy; theranostic agent
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Funding
- National Basic Research Program of China (973 Program) [2015CB755500]
- National Natural Science Foundation of China [51933011, 31971296, 21805314]
- Natural Science Foundation of Guangdong Province [2014A030312018]
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Ferroptosis is attracting significant attention due to its effectiveness in tumor treatment. The efficiency to produce toxic lipid peroxides (LPOs) at the tumor site plays a key role in ferroptosis. A hybrid PFP@Fe/Cu-SS metal organic framework (MOF) is synthesized and shown to increase intratumoral LPO content through redox reactions generating center dot OH. In addition, glutathione (GSH) depletion through disulfide-thiol exchange leads to the inactivation of glutathione peroxide 4 (GPX4), which results in a further increase in LPO content. This MOF exhibits high inhibitory effect on the growth of xenografted Huh-7 tumors in mice. The coadministration of a ferroptosis inhibitor reduces the antitumor effect of the MOF, leading to a restoration of GPX4 activity and an increase in tumor growth. Moreover, the construction of Cu into mesoporous PFP@Fe/Cu-SS not only allows the MOF to be used as a contrast agent forT(1)-weighted magnetic resonance imaging, but also renders its photothermal conversion capacity. Thus, near-infrared irradiation is able to induce photothermal therapy and transform the encapsulated liquid perfluoropentane into microbubbles for ultrasound imaging.
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