Magnetic resonance and fluorescence imaging superparamagnetic nanoparticles induce apoptosis and ferroptosis through photodynamic therapy to treat colorectal cancer

Reactive oxygen species (ROS)-based photodynamic therapy (PDT) has potential in the treatment of hollow organ tumors (eg, colorectal cancer, cholangiocarcinoma). However, the redox homeostasis and apoptosis tolerance of tumor cells limit the efficacy of this therapy, and more diverse forms of ROS-induced cell death need to be found to cope with tolerance. Here, we designed a nanoparticle with Fe₃O₄ as the core and BSA as the shell surface-modified with chlorin e6 (CE6) for ferroptosis-photodynamic therapy. Fe₃O₄@BSA-CE6 nanoparticles can release ferrous ions and CE6 in acidic TME. The CE6 is then able to generate ROS under laser irradiation to induce apoptosis. More importantly, under the catalysis of ferrous ions, the overloaded ROS and lipids generate lipid peroxides, thereby inducing ferroptosis in colorectal cancer cells. In addition, magnetic Fe₃O₄ provides excellent T2-weighted magnetic resonance imaging (MRI) properties. Therefore, due to the synergistic effect of inducing apoptosis and ferroptosis, the imaging ability, and the good safety of each component, Fe₃O₄@BSA-CE6 nanoparticles are expected to be used in clinical applications in the future.