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

Abstract 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 Fe 3 O 4 core that has MRI capability within a porous shell, this work synthesizes a series of core‐shell structured Fe 3 O 4 @carbon/copper oxide nanoparticles (Fe 3 O 4 @C/CuOx NPs) in which the Fe 3 O 4 core has different degrees of exposure. This work demonstrates that in an eccentric structure with maximally exposed Fe 3 O 4 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 Fe 3 O 4 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.