Cell internalization of anionic maghemite nanoparticles: quantitative effect on magnetic resonance imaging

Anionic iron oxide nanoparticles are efficiently internalized into macrophages where they concentrate within micrometric endosomes, conferring on them a high magnetic susceptibility. The uptake of anionic maghemite nanoparticles by macrophages was quantified by an electron spin resonance (ESR) experiment. MR spin-echo sequences were performed with various TEs and TRs. The contrast enhancement was compared between two types of agarose phantoms with the same equivalent ferrite concentrations but containing either dispersed isolated nanoparticles or magnetically labeled macrophages. It is shown that the intracellular confinement of maghemite nanoparticles within micrometric endosomes results in a significant decrease of the longitudinal relaxivity and a moderate decrease of the transverse relaxivity compared to the relaxivities of the dispersed isolated nanoparticles. As a consequence, the signature of endosomal magnetic labeling consists of a negative contrast on T(1)-weighted images in the whole ferrite concentration range, whereas the presence of extracellular isolated nanoparticles can result in a positive enhancement.