In vitro toxicity of nanoceria: effect of coating and stability in biofluids.

Due to the increasing use of nanometric cerium oxide in applications, concerns about the toxicity of these particles have been raised and have resulted in a large number of studies. We report here on the interactions between 7 nm anionically charged cerium oxide particles and living mammalian cells. By a modification of the particle coating including low-molecular weight ligands and polymers, two generic behaviours are compared: particles coated with citrate ions that precipitate in biofluids and particles coated with poly(acrylic acid) that are stable and remain nanometric. We find that nanoceria covered with both coating agents are taken up by mouse fibroblasts and localized into membrane-bound compartments. However, flow cytometry and electron microscopy reveal that as a result of their precipitation, citrate-coated particles interact more strongly with cells. At cerium concentration above 1 mM, only citrate-coated nanoceria (and not particles coated with poly(acrylic acid)) display toxicity and moderate genotoxicity. The results demonstrate that the control of the surface chemistry of the particles and its ability to prevent aggregation can affect the toxicity of nanomaterials.

Shape transition in artificial tumors: from smooth buckles to singular creases.

Using swelling hydrogels, we study the evolution of a thin circular artificial tumor whose growth is confined at the periphery. When the volume of the outer proliferative ring increases, the tumor loses its initial symmetry and bifurcates towards an oscillatory shape. Depending on the geometrical and elastic parameters, we observe either a smooth large-wavelength undulation of the swelling layer or the formation of sharp creases at the free boundary. Our experimental results as well as previous observations from other studies are in very good agreement with a nonlinear poroelastic model.

Interactions between magnetic nanowires and living cells: uptake, toxicity, and degradation.

We report on the uptake, toxicity, and degradation of magnetic nanowires by NIH/3T3 mouse fibroblasts. Magnetic nanowires of diameters 200 nm and lengths between 1 and 40 µm are fabricated by controlled assembly of iron oxide (γ-Fe(2)O(3)) nanoparticles. Using optical and electron microscopy, we show that after 24 h incubation the wires are internalized by the cells and located either in membrane-bound compartments or dispersed in the cytosol. Using fluorescence microscopy, the membrane-bound compartments were identified as late endosomal/lysosomal endosomes labeled with lysosomal associated membrane protein (Lamp1). Toxicity assays evaluating the mitochondrial activity, cell proliferation, and production of reactive oxygen species show that the wires do not display acute short-term (<100 h) toxicity toward the cells. Interestingly, the cells are able to degrade the wires and to transform them into smaller aggregates, even in short time periods (days). This degradation is likely to occur as a consequence of the internal structure of the wires, which is that of a noncovalently bound aggregate. We anticipate that this degradation should prevent long-term asbestos-like toxicity effects related to high aspect ratio morphologies and that these wires represent a promising class of nanomaterials for cell manipulation and microrheology.

Structure and thermorheology of concentrated pluronic copolymer micelles in the presence of laponite particles.

Small-angle neutron scattering and thermorheology techniques are used to investigate in detail the effect of laponite particles in aqueous solutions of poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide), PEO-PPO-PEO, block copolymers in the concentrated regime. At high polymer concentration or temperature, the micellar solutions exhibit a phase transition from fluid to crystal due to crowding of the micelles. The addition of laponite is found to disturb this phase transition. The adsorption of the copolymer unimers onto laponite in large amounts describes these findings. It is shown that the preferred adsorption of the copolymer chains results in a sufficient increase in free volume for the remaining micelles to yield the observed enhancement of the structural disorder.

Phase behavior and microstructure of microemulsions containing the hydrophobic ionic liquid 1-butyl-3-methylimidazolium hexafluorophosphate.

The phase behavior and microstructure of the ternary system water/1-butyl-3-methylimidazolium hexafluorophosphate (bmimPF(6))/Triton X-100 was studied as a function of temperature and ionic liquid (IL) mass fraction alpha. In the present study, a hydrophobic IL instead of commonly used organic solvents such as n-alkanes is used. The fish-shaped region is distorted at low and high values of alpha, whereas it is symmetric at intermediate alpha. With increasing alpha, the extension of the three-phase region decreases regarding the surfactant concentration range, whereas it increases regarding the temperature range. For comparison the phase behavior of two ternary water/bmimPF(6)/alkyl oligoethyleneoxide (C(i)E(j)) systems has been investigated. Our results are compared with those obtained for water/n-alkane/C(i)E(j) and IL/n-alkane/C(i)E(j) systems, respectively.

Shear-induced permeation and fusion of lipid vesicles.

This paper introduces a novel approach to controlling membrane permeability in free unilamellar vesicles using shearing in the presence of a detergent with a large head-group to tune pore formation. Such shear-induced permeation could offer a simple means of postencapsulating bioactive molecules to prepare vesicle vectors for drug delivery. Using UV absorption, fluorescence emission, dynamic light scattering, and electron microscopy, we investigated the membrane permeability and the morphology of unilamellar lipid vesicles (diameter in the range 50-400 nm) subjected to a shear stress in the presence of a small amount of nonionic surfactant (Brij 76). Shear-induced leakage and fusion events were observed. We analyzed the significance of the vesicle size, the shear rate, and the surfactant-to-lipid ratio for the observed phenomena. The present approach is evaluated for postloading of preformed vesicles.

Fusogenic supramolecular vesicle systems induced by metal ion binding to amphiphilic ligands.

The incorporation of lipophilic ligands into the bilayer membrane of vesicles offers the possibility to induce, upon binding of suitable metal ions, a variety of processes, in particular vesicle aggregation and fusion and generation of vesicle arrays, under the control of specific metal-ligand recognition events. Synthetic bipyridine lipoligands Bn bearing a bipyridine unit as head group were prepared and incorporated into large unilamellar vesicles. The addition of Ni2+ or Co2+ metal ions led to the formation of complexes MBn and MBn2 followed by spontaneous fusion to generate giant multilamellar vesicles. The metal ion complexation was followed by UV spectroscopy and the progressive fusion could be visualized by optical dark-field and fluorescence microscopies. Vesicle fusion occurred without leakage of the aqueous compartments and resulted in the formation of multilamellar giant vesicles because of the stacking of the lipoligands Bn. The fusion process required a long enough oligoethylene glycol spacer and a minimal concentration of lipoligand within the vesicle membrane. Metallosupramolecular systems such as the present one offer an attractive way to induce selective intervesicular processes, such as vesicle fusion, under the control of molecular recognition between specific metal ions and lipoligands incorporated in the bilayer membrane. They provide an approach to the design of artificial "tissue-mimetics" through the generation of polyvesicular arrays of defined architecture and to the control of their functional properties.

Budding and tubulation in highly oblate vesicles by anchored amphiphilic molecules.

We studied local budding and tubulation induced in highly oblate lipid vesicles by the anchoring of either polymers having a hydrophilic backbone and grafted hydrophobic anchor groups, or by oleoyl-coenzyme A, an amphiphilic molecule important in lipid metabolism. The dynamics of bud formation, shrinkage, and readsorption is consistent with an induced spontaneous curvature coupled with local amphiphile diffusion on the membrane. We report a novel metastable state prior to bud readsorption.

Raspberry vesicles.

We present a method to control the osmotic stress of giant unilamellar vesicles (GUV) and we report an original shrinkage mode of the vesicles: the volume reduction is accompanied by the formation of inverted daughter vesicles which gives the shrunk vesicles the appearance of raspberries. We analyze this peculiar shrinkage and we propose some physical origins for the observed phenomena.