Abstract
Chemodynamic therapy (CDT) is a booming technology that utilizes Fenton reagents to kill tumor cells by transforming intracellular H(2)O(2) into reactive oxygen species (ROS), but insufficient endogenous H(2)O(2) makes it difficult to attain satisfactory antitumor results. In this article, a H(2)O(2)-free CDT technique with tumor-specificity is developed by using pH-sensitive magnetic iron carbide nanoparticles (PEG/Fe(2)C@Fe(3)O(4) NPs) to trigger artemisinin (ART) to in situ form ROS. ART-loaded PEG/Fe(2)C@Fe(3)O(4) NPs are fabricated for the enormous release of Fe(2+) ions induced by the acidic conditions of the tumor microenvironment after magnetic-assisted tumor enrichment, which results in the rapid degradation of the PEG/Fe(2)C@Fe(3)O(4) NPs and release of ART once endocytosed into tumor cells. In situ catalysis reaction between the co-released Fe(2+) 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 H(2)O(2)-independent ROS generation.