Peroxidase-like Fe3O4 nanocomposite for activatable reactive oxygen species generation and cancer theranostics

Abstract

Photodynamic therapy (PDT) that utilizes apoptosis induced by reactive oxygen species (ROS) has received extensive attention in practical cancer therapy. However, the hypoxic microenvironment of solid tumors significantly limits the efficacy of therapy. Approaches that overcome the barriers to PDT in hypoxic conditions by simultaneously producing ROS exogenously and improving the oxygenation of tumors have never been studied. Herein, an activatable ROS platform was designed that uses the high reactivity of peroxidase-like Fe₃O₄ toward endogenous hydrogen peroxide (H₂O₂) to concurrently generate ˙OH as a therapeutic agent and provide O₂ for oxygen-dependent PDT. Multifunctional chitosan-encapsulated Fe₃O₄ nanoparticles modified with CuS and porphyrin (FCCP NPs) were fabricated to achieve multimodal imaging and synergetic therapy. The FCCP NPs possess enhanced intrinsic peroxidase mimetic activity to produce ROS and O₂ from endogenous H₂O₂. Multimodal imaging in vivo, including photoacoustic imaging (PAI), magnetic resonance imaging (MRI), photoluminescence imaging (PLI), and photothermal imaging (PTI), exploits the tumor-targeting property of FCCP NPs upon intravenous injection. It can induce cancer cell death with remarkable efficiency both in vitro and in vivo via synergetic treatment with PDT and photothermal therapy (PTT). This study demonstrates the promise of the activatable generation of ROS and O₂ for PDT with nanotechnology to overcome a current deficiency in cancer therapies.