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 towards
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.Comment: 21 pages, 11 figures, accepted at Biomaterials (2011
