Magnetic Particle Imaging Distinguishes Viable and Damaged Cells by Exploiting Distinct Magnetic Signatures of Internalized Nanoparticles

Magnetic particle imaging (MPI) enables quantitative and highly sensitive detection of magnetically labeled cells. Yet, MPI has mainly been applied to spatial cell tracking rather than assessing cell physiology. Here, MPI is expanded toward functional cell tracking by exploiting cell physiology‐dependent magnetic signatures using color MPI. THP1 cells were labeled with a citrate‐coated iron oxide nanoparticle system (Synomag‐COOH, SynC). Labeling preserved immune cell functions, without inducing oxidative stress, inflammasome activation, or altering adhesion to the inflamed endothelium. Magnetic particle spectroscopy (MPS) revealed that intracellular processing and extracellular oxidative stress modify the magnetic signature of internalized nanoparticles, reflected in changes to key MPS parameters: A 3 , A 5 /A 3 ratio, and ϕ 3 . Nanoparticles internalized by dividing and nondividing cells exhibited opposite A 5 /A 3 trends over 72 h, which indicated that cell type and intracellular processing distinctly modulate the magnetic signatures. Exposure to extracellular oxidative stress induced a distinct magnetic signature of internalized SynC. Color MPI successfully visualized these magnetic signature differences between oxidatively damaged and viable cells within mixed populations. These findings demonstrated that cell physiological modulation of the magnetic signatures of internalized nanoparticles enables simultaneous mapping of cell location and physiology. This established a proof‐of‐principle for a magnetic nanoparticle‐based approach that might enable monitoring of cell state during regenerative and immunotherapies.