Ligand-mediated acid-activatable magnetic particle imaging probes for highly sensitive diagnosis of sepsis

Magnetic particle imaging (MPI) holds immense promise as a non-invasive biomedical imaging modality, but its advancement is hindered by the absence of activatable probes for biomarker-specific imaging. Here, we introduce a ligand-mediated acid-activatable MPI probe (LAMP) composed of magnetic nanoparticles linked via acid-sensitive imine bond-containing ligands. The LAMP exhibits stable assembly in neutral conditions and rapid disassembly in acidic microenvironments. The imine bond crosslinking promotes a compact structure that enhances magnetic dipole interactions, significantly quenching the initial MPI signal. Upon exposure to acidic conditions, the probe disassembles, restoring the MPI signal in a highly controlled, environment-dependent manner. This switchable assembly enables precise, real-time imaging of acidity-associated diseases such as sepsis progression. Our findings demonstrate that the ligand-mediated modulation of magnetic dipole interactions provides a versatile platform for the design of next-generation MPI probes for biomarker-specific MPI imaging.