Feasibility of using ultrasmall magnetoferritin particles for magnetic particle imaging

Magnetic particle imaging (MPI) is an emerging in vivo imaging modality that offers high sensitivity, high contrast, and no depth limitation. It has demonstrated significant potential in pre-clinical research and holds promise for clinical translation. Currently, iron oxide nanoparticles with diameters between 15 and 25 nm are predominantly used as tracers in MPI. While particles smaller than 10 nm exhibit prolonged blood circulation and reduced liver uptake, they are generally deemed as unsuitable for MPI due to their inability to produce nonlinear magnetization response. In this study, we discovered that 5 nm magnetoferritin particles accumulate in lysosomes after being internalized by cells with high TfR1 expression and can efficiently generate MPI signals. Our findings were validated both at the cellular level and in vivo using animal tumor models. This work represents the first demonstration that ultrasmall superparamagnetic iron oxide particles (USPIOs) can be utilized for MPI imaging, providing a critical foundation for the development of activated MPI imaging technique and USPIO-based MPI probes.