4.6 Article

H2O2-independent chemodynamic therapy initiated from magnetic iron carbide nanoparticle-assisted artemisinin synergy

Journal

RSC ADVANCES
Volume 11, Issue 59, Pages 37504-37513

Publisher

ROYAL SOC CHEMISTRY
DOI: 10.1039/d1ra04975e

Keywords

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Funding

  1. National Natural Science Foundation of China (NSFC) [52073258, 51602285, 81701821]
  2. Natural Science Foundation of Zhejiang Province [LY20E020017, LQ19H160016]
  3. Young Elite Scientist Sponsorship Program by CAST [2017QNRC001]
  4. Fundamental Research Funds for the Provincial Universities of Zhejiang [RF-A2019004]
  5. Open Project Program of MOE Key Laboratory of Drug Quality Control and Pharmacovigilance [DQCP20/21MS02]
  6. Foundation of Health Department of Zhejiang Province [2018KY239, 2019RC010]
  7. Technological Program of Zhejiang Traditional Medicine [2019ZB014]

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This article introduces a H2O2-free chemodynamic therapy technique with tumor-specificity using pH-sensitive magnetic iron carbide nanoparticles to trigger the production of reactive oxygen species, resulting in effective tumor cell apoptosis. The study demonstrates enhanced and tumor-specific CDT efficacy for effective tumor inhibition based on ROS generation, offering a new direction to improve CDT efficacy without relying on H2O2.
Chemodynamic therapy (CDT) is a booming technology that utilizes Fenton reagents to kill tumor cells by transforming intracellular H2O2 into reactive oxygen species (ROS), but insufficient endogenous H2O2 makes it difficult to attain satisfactory antitumor results. In this article, a H2O2-free CDT technique with tumor-specificity is developed by using pH-sensitive magnetic iron carbide nanoparticles (PEG/Fe2C@Fe3O4 NPs) to trigger artemisinin (ART) to in situ form ROS. ART-loaded PEG/Fe2C@Fe3O4 NPs are fabricated for the enormous release of Fe2+ ions induced by the acidic conditions of the tumor microenvironment after magnetic-assisted tumor enrichment, which results in the rapid degradation of the PEG/Fe2C@Fe3O4 NPs and release of ART once endocytosed into tumor cells. In situ catalysis reaction between the co-released Fe2+ ions and ART generates toxic ROS and then induces apoptosis of tumor cells. Both in vitro and in vivo experiments demonstrate that the efficient Fe-enhanced and tumor-specific CDT efficacy for effective tumor inhibition based on ROS generation. This work provides a new direction to improve CDT efficacy based on H2O2-independent ROS generation.

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