UPTAKE OF DEXTRAN-COATED MONOCRYSTALLINE IRON-OXIDES IN TUMOR-CELLS AND MACROPHAGES

Although several dextran-coated iron oxide preparations are in preclin ical and clinical use, little Is known about the mechanism of uptake i nto cells, As these particles have been shown to accumulate in macroph ages and tumor cells, we performed cellular uptake and inhibition stud ies with a prototypical monocrystalline iron oxide nanoparticle (MION) . MION particles were labeled with fluorescein Isothiocyanate or radio iodinated and purified by gel permeation chromatography. Two preparati ons of MION particles were used in cell experiments: nontreated MION a nd plasma-opsonized MION purified by gradient density purification. As determined by immunoblotting, opsonization resulted in C3, vitronecti n, and fibronectin association with MION. Incubation of cells with flu orescent MION showed active uptake of particles in macrophages both be fore and after opsonization, In C6 tumor cells, however. intracellular MION was only detectable in dividing cells, Quantitatively, I-125-lab eled MION was internalized into cells with uptake values ranging from 17 ng (in 9L gliosarcoma) to 970 ng iron per million cells for periton eal macrophages. Opsonization increased MION uptake into macrophages s ixfold, whereas it increased the uptake in C6 tumor cells only twofold , Results from uptake inhibition assay suggest that cellular uptake of nonopsonized (dextran-coated) MION particles is mediated by fluid-pha se endocytosis, whereas receptor-mediated endocytosis is presumably re sponsible for the uptake of opsonized (protein-coated) particles.