Single-atom and clustered iron-embedded graphitic nitrogen-doped carbon nanospheres for cancer imaging and ferroptosis

Despite development in nanozymes for cancer treatment, challenges in their synthesis and structural optimization for peak catalytic activity persist. A multifunctional enzyme-like nanoparticle using a controllable synthesis that offers a clear structure–activity relationship was developed. The nitrogen-doped mesoporous carbon nanospheres (MCNs) with iron coordination were produced via an in-situ iron-catalyzed pyrolysis, which allowed for precise adjustment of iron content. Not only do Fe/MCN exhibit high graphitization for enhanced photothermal conversion but also feature co-doping with both single atoms and atom clusters, enhancing their enzyme-like activities. These activities included oxidase, peroxidase, catalase, and glutathione oxidase, leading to synergistic effects in chemodynamic, photodynamic therapies, and hypoxia alleviation. Additionally, Fe/N-MCNs induced potent immunogenic cell death, aided by ROS, ferroptosis, and ferroptosis-sensitized photothermal therapy. Fe/N-MCN also provided excellent photoacoustic and magnetic resonance imaging capabilities, establishing a multifaceted platform for the treatment of breast cancer and the inhibition of postoperative recurrence and metastasis.