Labeling of cancer cells with magnetic nanoparticles for magnetic resonance imaging.

PURPOSE: The process of invasion and metastasis formation of tumor cells can be studied by following the migration of labeled cells over prolonged time periods. This report investigates the applicability of iron oxide nanoparticles as a magnetic resonance imaging (MRI) contrast agent for cell labeling. METHODS: γFe2 O3 nanoparticles prepared with direct flame spray pyrolysis are biofunctionalized with poly-l-lysine (PLL). The nanoparticles within the cells were observed with transmission electron microscopy, bright-field microscopy, and magnetorelaxometry. MRI of labeled cells suspended in agarose was used to estimate the detection limit. RESULTS: PLL-coated particles are readily taken up, stored in intracellular clusters, and gradually degraded by the cells. During cell division, the nanoparticle clusters are divided and split between daughter cells. The MRI detection limit was found to be 25 cells/mm(3) for R2*, and 70 cells/mm(3) for R2. The iron specificity, however, was higher for R2 images. Due to the degradation of intracellular γFe2 O3 to paramagnetic iron ions within 13 days, the R1, R2, and R2* contrast gradually decreased over this time period to approximately 50% of its initial value. CONCLUSIONS: These results suggest that PLL-coated γFe2 O3 nanoparticles can be used as an MRI contrast agent for long-term studies of cell migration. Magn Reson Med 71:1896-1905, 2014. © 2013 Wiley Periodicals, Inc.

The effect of polymer coatings on proton transverse relaxivities of aqueous suspensions of magnetic nanoparticles.

Iron oxide magnetic nanoparticles are good candidates for magnetic resonance imaging (MRI) contrast agents due to their high magnetic susceptibilities. Here we investigate 19 polyether-coated magnetite nanoparticle systems comprising three series. All systems were synthesized from the same batch of magnetite nanoparticles. A different polyether was used for each series. Each series comprised systems with systematically varied polyether loadings per particle. A highly significant (p < 0.0001) linear correlation (r = 0.956) was found between the proton relaxivity and the intensity-weighted average diameter measured by dynamic light scattering in the 19 particle systems studied. The intensity-weighted average diameter measured by dynamic light scattering is sensitive to small number fractions of larger particles/aggregates. We conclude that the primary effect leading to differences in proton relaxivity between systems arises from the small degree of aggregation within the samples, which appears to be determined by the nature of the polymer and, for one system, the degree of polymer loading of the particles. For the polyether coatings used in this study, any changes in relaxivity from differences in water exclusion or diffusion rates caused by the polymer are minor in comparison with the changes in relaxivity resulting from variations in the degree of aggregation.

Experimental validation of proton transverse relaxivity models for superparamagnetic nanoparticle MRI contrast agents.

Analytical models of proton transverse relaxation rate enhancement by magnetic nanoparticles were tested by making measurements on model experimental systems in a field of 1.4 T. Proton relaxivities were measured for five aqueous suspensions of iron oxide (maghemite) nanoparticles with nominal mean particle sizes of 6, 8, 10, 11, and 13 nm. Proton relaxivity increased with mean particle size ranging from 13 s(-1) mM Fe(-1) for the 6 nm sample, up to 254 s(-1) mM Fe(-1) for the 13 nm sample. A strong correlation between the measured and predicted values of the relaxivity was observed, with the predicted values being consistently higher than the measured values. The results indicate that the models give a reasonable agreement with experimental results and hence can be used as the basis for the design of new magnetic resonance imaging contrast and labelling agents.

Nanostructure of PEO-polyurethane-PEO triblock copolymer micelles in water.

Novel hydrophilic triblock copolymers which form micelles in aqueous solution were studied by static and dynamic light scattering (SLS and DLS), small angle neutron scattering (SANS) and densitometry. The polymers were symmetric A-B-A block copolymers having two poly(ethylene oxide) (PEO) tail blocks and a polyurethane (PU) center segment that contained pendant carboxylic acids. The aggregation number of the micelles decreased with increasing PEO mass content. When attempting to fit the SANS data it was found that no single model was suitable over the entire range of block lengths and PEO mass concentrations investigated here. For the polymer with the highest aggregation number, the data were fitted with a triblock model consisting of a homogeneous core with a corona of non-interacting Gaussian chains for which only two free parameters were required: the radius of the core and the radius of gyration of the corona. In this case, the core was found to be effectively dry. At lower aggregation numbers, a star polymer model generated significantly better fits, suggesting the absence of any identifiable central core structure. Good agreement was found between the sizes measured by DLS, SANS and theoretical predictions of micelle size from a density distribution theory. These results show that when significant changes in aggregation number occur, the nanostructure of the micelle can change substantially even for polymers that are remarkably similar.

Stability of polydimethylsiloxane-magnetite nanoparticle dispersions against flocculation: interparticle interactions of polydisperse materials.

The colloidal stability of dispersions comprised of magnetite nanoparticles coated with polydimethylsiloxane (PDMS) oligomers was investigated theoretically and experimentally. Particle-particle interaction potentials in a theta solvent and in a good solvent for the PDMS were predicted by calculating van der Waals, electrostatic, steric, and magnetic forces as functions of interparticle separation distances. A variety of nanoparticle sizes and size distributions were considered. Calculations of the interparticle potential in dilute suspensions indicated that flocculation was likely for the largest 1% of the population of particles. Finally, the rheology of these complexes over time in the absence of a solvent was measured to probe their stabilities against flocculation as neat fluids. An increase in viscosity was observed upon aging, suggesting that some agglomeration occurs with time. However, the effects of aging could be removed by exposing the sample to high shear, indicating that the magnetic fluids were not irreversibly flocculated.