Redox Responsive Metal Organic Framework Nanoparticles Induces Ferroptosis for Cancer Therapy.

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Haozhe HeXintao Shuai

Abstract

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 ·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 for T1 -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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Citations

Mar 2, 2021·ACS Applied Materials & Interfaces·Benson Peter MugakaXing-Hua Xia
Jun 24, 2021·Biomaterials Science·Hajra ZafarQi Shen
Sep 2, 2021·Bioactive Materials·Lei WuJun Yue
Sep 11, 2021·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Qun GuanYu-Bin Dong
Nov 4, 2021·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Jiaoyang TaoWeidong Fei

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