Eccentric Nanozymes with Maximally Exposed Fe ₃ O ₄ Core for Optimal MR Imaging and Mesoporous Shell That Delivers Chemotherapy and Cuproptosis

Combing magnetic resonance imaging (MRI) and cancer therapy modalities within one nanoplatform holds great potential for imaging-guided cancer theranostics. However, simultaneously achieving optimal MRI performance and satisfactory anti-cancer effects is still a challenge. Here, by manipulating the position of a Fe₃O₄ core that has MRI capability within a porous shell, this work synthesizes a series of core-shell structured Fe₃O₄@carbon/copper oxide nanoparticles (Fe₃O₄@C/CuOx NPs) in which the Fe₃O₄ core has different degrees of exposure. This work demonstrates that in an eccentric structure with maximally exposed Fe₃O₄ core, the NPs exhibits optimal MRI capability. Additionally, using polymer as scaffold blended with carbon-doped copper oxide, the shell of the NPs can integrate chemotherapy, photothermal therapy (PTT) and cuproptosis to exert synergistic anti-cancer effect in a pH/NIR dual responsive manner. The porous shell allows efficient DOX loading for chemotherapy, the copper oxide component serves as photothermal agents for PTT and triggers for cuproptosis. Last, the Fe₃O₄ core is also a nanozyme that possesses peroxidase (POD)-like properties, which enhances the efficacy of above-mentioned anti-cancer effects via promoting reactive oxygen species (ROS) generation. This work evaluates the MRI-guided anti-cancer efficacy of the NPs both in vitro and in vivo, and demonstrates NPs' superior performance in imaging-guided cancer theranostics.