Peroxidase-like Fe3O4 Nanocomposite for Activatable Reactive Oxygen Species Generation and Cancer Theranostics
Abstract
Photodynamic therapy (PDT) that utilizes the reactive oxygen species (ROS)-induced apoptosis has received extensive attention for practical cancer therapy. However, the hypoxia solid tumor microenvironment significantly resists the therapy efficacy. The approaches that overcome the hypoxic PDT by simultaneously producing ROS exogenously and improving the oxygenation of tumors have never been explored. Herein, an activatable ROS platform is designed that use the high reactivity peroxidase-like Fe3O4 toward endogenous hydrogen peroxide (H2O2) to concurrently generate the •OH as therapeutic element and provide O2 for oxygen-relied PDT. Multifunctional chitosan-encapsulated Fe3O4 nanoparticles with CuS and porphyrin modification (FCCP NPs) are fabricated to achieve multimode imaging and synergetic therapy. The FCCP NPs possess a strengthened intrinsic peroxidase mimetic activity to induce ROS and O2 from endogenous H2O2. Multimode imaging in vivo including photoacoustic imaging (PAI), magnetic resonance imaging (MRI), photoluminescence imaging (PLI), and photothermal imaging (PTI) track the tumor homing property of FCCP NPs upon intravenous injection. It can induce remarkably efficient cancer cell death both in vitro and in vivo through synergetic treatment of PDT and photothermal therapy (PTT). This study demonstrates the promise of activatable ROS and O2 generation for PDT with nanotechnology to surmount the current deficiency of cancer therapies.
