Magnetic Reactive Oxygen Species Nanoreactor for Switchable Magnetic Resonance Imaging Guided Cancer Therapy Based on pH-Sensitive Fe₅C₂@Fe₃O₄ Nanoparticles

Abstract

Reactive oxygen species (ROS) are crucial molecules in cancer therapy. Unfortunately, the therapeutic efficiency of ROS is unsatisfactory in clinic, primarily due to their rigorous production conditions. By taking advantage of the intrinsic acidity and overproduction of H₂O₂ in the tumor environment, we have reported an ROS nanoreactor based on core-shell-structured iron carbide (Fe₅C₂@Fe₃O₄) nanoparticles (NPs) through the catalysis of the Fenton reaction. These NPs are able to release ferrous ions in acidic environments to disproportionate H₂O₂ into ^•OH radicals, which effectively inhibits the proliferation of tumor cells both <i>in vitro</i> and <i>in vivo</i>. The high magnetization of Fe₅C₂@Fe₃O₄ NPs is favorable for both magnetic targeting and <i>T</i>₂-weighted magnetic resonance imaging (MRI). Ionization of these NPs simultaneously decreases the <i>T</i>₂ signal and enhances the <i>T</i>₁ signal in MRI, and this <i>T</i>₂/<i>T</i>₁ switching process provides the visualization of ferrous ions release and ROS generation for the supervision of tumor curing. These Fe₅C₂@Fe₃O₄ NPs show great potential in endogenous environment-excited cancer therapy with high efficiency and tumor specificity and can be guided further by MRI.