A light-activated Fe2+ release nanosystem for enhanced chemodynamic/chemo therapy via cascade amplification of ROS generation

Abstract

Ferrous iron (Fe2+)-based chemodynamic therapy (CDT) shows great potential for improving chemotherapeutic efficacy and reducing side effects. However, the spontaneous oxidation and biological matrixes can influence the catalytic ROS generation of Fe2+, thus limiting the efficacy of CDT. Here, we reported a simple and convenient method to construct hyaluronic acid (HA)-stabilized iron/zinc oxide nanoparticles (IZ@H NPs), which showed intrinsic peroxidase (POD)-like activity and excellent light-activated Fe2+ release performance. Moreover, we demonstrated the catalytic reactive oxygen species (ROS) showed a cascade amplification manner due to light-activated Fe2+ release from IZ@H NPs to form iron-DNA complexes (IDCs). After loading doxorubicin (DOX), the nanosystem (termed IZD@H NPs) showed tumor cells targeting, robust ROS generation and high cytotoxicity, thereby significant suppressing tumor growth in tumor xenograft mice models and showing good biosafety. This work gives a novel insight into amplifying catalytic ROS generation of Fe2+, and provides a new strategy to in vivo Fe2+ delivery for enhanced chemodynamic/chemo therapy.