title: The effects of aggregation and protein corona on the cellular internalization of iron oxide nanoparticles.
abstract: Engineered inorganic nanoparticles are essential components in the development of nanotechnologies. For applications in nanomedicine, particles need to be functionalized to ensure a good dispersibility in biological fluids. In many cases however, functionalization is not sufficient: the particles become either coated by a corona of serum proteins or precipitate out of the solvent. In the present paper, we show that by changing the coating of iron oxide nanoparticles from a low-molecular weight ligand (citrate ions) to small carboxylated polymers (poly(acrylic acid)), the colloidal stability of the dispersion is improved and the adsorption/internalization of iron toward living mammalian cells is profoundly affected. Citrate-coated particles are shown to destabilize in all fetal-calf-serum based physiological conditions tested, whereas the polymer coated particles exhibit an outstanding dispersibility as well as a structure devoid of protein corona. The interactions between nanoparticles and human lymphoblastoid cells are investigated by transmission electron microscopy and flow cytometry. Two types of nanoparticle/cell interactions are underlined. Iron oxides are found either adsorbed on the cellular membranes, or internalized into membrane-bound endocytosis compartments. For the precipitating citrate-coated particles, the kinetics of interactions reveal a massive and rapid adsorption of iron oxide on the cell surfaces. The quantification of the partition between adsorbed and internalized iron was performed from the cytometry data. The results highlight the importance of resilient adsorbed nanomaterials at the cytoplasmic membrane.
authors.affiliation: Matière et Systèmes Complexes, UMR 7057 CNRS Université Denis Diderot Paris-VII, Bâtiment Condorcet 10 rue Alice Domon et Léonie Duquet, 75205 Paris, France.
authors.forename: M
authors.initials: M
authors.lastname: Safi
authors.forename: J
authors.initials: J
authors.lastname: Courtois
authors.forename: M
authors.initials: M
authors.lastname: Seigneuret
authors.forename: H
authors.initials: H
authors.lastname: Conjeaud
authors.forename: J-F
authors.initials: JF
authors.lastname: Berret
mesh_terms: D000180:Acrylic Resins / Q000737:chemistry; D000327:Adsorption / Q000187:drug effects; D001798:Blood Proteins / Q000737:chemistry / Q000378:metabolism*; D002951:Citrates / Q000737:chemistry; D003102:Colloids; D003470:Culture Media / Q000494:pharmacology; D004705:Endocytosis / Q000187:drug effects; D005290:Ferric Compounds / Q000378:metabolism*; D005434:Flow Cytometry; D006801:Humans; D057446:Hydrodynamics; D008027:Light; D008970:Molecular Weight; D053758:Nanoparticles / Q000737:chemistry / Q000648:ultrastructure; D011485:Protein Binding; D020836:Protein Structure, Quaternary; D012542:Scattering, Radiation
chemical_list: D000180:Acrylic Resins; D001798:Blood Proteins; D002951:Citrates; D003102:Colloids; D003470:Culture Media; D005290:Ferric Compounds; C000499:ferric oxide; C006903:carbopol 940