Magnesium hexacyanoferrate nanocatalysts attenuate chemodrug-induced cardiotoxicity through an anti-apoptosis mechanism driven by modulation of ferrous iron.

Abstract

Distressing and lethal cardiotoxicity is one of the major severe side effects of using anthracycline drugs such as doxorubicin for cancer chemotherapy. The currently available strategy to counteract these side effects relies on the administration of cardioprotective agents such as Dexrazoxane, which unfortunately has unsatisfactory efficacy and produces secondary myelosuppression. In the present work, aiming to target the characteristic ferrous iron overload in the doxorubicin-contaminated cardiac microenvironment, a biocompatible nanomedicine prepared by the polyvinylpyrrolidone-directed assembly of magnesium hexacyanoferrate nanocatalysts is designed and constructed for highly efficient intracellular ferrous ion capture and antioxidation. The synthesized magnesium hexacyanoferrate nanocatalysts display prominent superoxide radical dismutation and catalytic H2O2 decomposition activities to eliminate cytotoxic radical species. Excellent in vitro and in vivo cardioprotection from these magnesium hexacyanoferrate nanocatalysts are demonstrated, and the underlying intracellular ferrous ion traffic regulation mechanism has been explored in detail. The marked cardioprotective effect and biocompatibility render these magnesium hexacyanoferrate nanocatalysts to be highly promising and clinically transformable cardioprotective agents that can be employed during cancer treatment.

• Authors: Minfeng Huo, Zhimin Tang, Liying Wang, Linlin Zhang, Haiyan Guo, Yu Chen, Ping Gu, Jianlin Shi
• Journal: Nature communications (Nat Commun) Vol. 13 Issue 1 Pg. 7778 (12 15 2022) ISSN: 2041-1723 [Electronic] England
• PMID: 36522337 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2022. The Author(s).

Chemical References

• hexacyanoferrate II
• Magnesium
• Cardiotonic Agents
• Iron
• Hydrogen Peroxide
• Doxorubicin

Topics

• Humans
• Cardiotoxicity (drug therapy)
• Magnesium
• Cardiotonic Agents (pharmacology)
• Iron (therapeutic use)
• Hydrogen Peroxide
• Doxorubicin (toxicity)