Responsive Ordered Assembly of Magnetic Nanoparticles for ROS Activatable Magnetic Particle Imaging

Abstract Magnetic particle imaging (MPI) has emerged as a versatile biomedical imaging modality, yet a significant challenge persists in the absence of activatable MPI probes for targeted imaging of disease biomarkers. In this study, a reactive oxygen species (ROS)‐responsive ordered assembly of magnetic nanoparticles (MNPs) is reported, engineered through the meticulous design of magnetic nanoparticle building blocks and ROS‐responsive polymeric ligands, enabling precise control over the assembly structure. This ordered configuration amplifies magnetic dipole‐dipole interactions, raising the energy barrier during nonequilibrium dynamic magnetization and effectively quenching the MPI signal. By modulating the assembly and disassembly of these ordered structures in response to ROS, this nanoprobe achieves ROS‐dependent off/on MPI signal regulation. Consequently, the probe enables the monitoring of early pathological ROS change in a mice model of early acute liver injury, facilitating highly sensitive monitoring of the ROS level‐dependent severity of the disease. This work represents the inaugural application of microenvironment‐responsive MPI probes for the early diagnosis of ROS‐associated diseases. The introduction of ordered assembly structures for MPI signal tuning offers a promising translational approach in the development of next‐generation activatable MPI probes.