An Efficient Magnetic Nanocatalyst Induced Chemo- and Ferroptosis Synergistic Cancer Therapy in Combination with T1-T2 Dual-Mode Magnetic Resonance Imaging through Doxorubicin Delivery

Abstract Excessive iron ions in cancer cells can catalyze H2O2 into highly toxic ·OH and then promote the generation of reactive oxygen species (ROS), inducing cancer ferroptosis. However, the efficacy of ferroptosis catalyst is still insufficient because of low Fe(II) release, which severely limited its application in clinics. Herein, we developed a novel magnetic nanocatalyst for MRI-guided chemo- and ferroptosis synergistic cancer therapies through iRGD-PEG-ss-PEG modified gadolinium engineering magnetic iron oxide loaded Dox (ipGdIO-Dox). The introduction of gadolinium compound disturbed the structure of ipGdIO-Dox, making magnetic nanocatalyst be more sensitive to weak acid. When the ipGdIO-Dox entered into cancer cells, abundance of Fe(II) ions were released and then catalyzed H2O2 into highly toxic OH·, which would elevate cellular oxidative-stress to damage mitochondria and cell membranes and induced cancer ferroptosis. In addition, the iRGD-PEG-ss-PEG chain coated onto nanoplatform were also broken by high expression of GSH, and then the Dox was released. This process not only effectively inhibited DNA replication, but further activated cellular ROS, making nanoplatform achieve stronger anticancer ability. Besides, the systemic delivery ipGdIO-Dox significantly enhanced T1- and T2-weighted MRI signal of tumor, endowing accurate diagnostic capability for tumor recognition. Therefore, the ipGdIO-Dox might be a promising candidate for developing MRI guided chemo- and chemdynamic synergistic theranostic system.