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

Abstract

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.