Reversible and irreversible aggregation of magnetic liposomes.

Understanding stabilization and aggregation in magnetic nanoparticle systems is crucial to optimizing the functionality of these systems in real physiological applications. Here we address this problem for a specific, yet representative, system. We present an experimental and analytical study on the aggregation of superparamagnetic liposomes in suspension in the presence of a controllable external magnetic field. We study the aggregation kinetics and report an intermediate time power law evolution and a long time stationary value for the average aggregate diffusion coefficient, both depending on the magnetic field intensity. We then show that the long time aggregate structure is fractal with a fractal dimension that decreases upon increasing the magnetic field intensity. By scaling arguments we also establish an analytical relation between the aggregate fractal dimension and the power law exponent controlling the aggregation kinetics. This relation is indeed independent on the magnetic field intensity. Despite the superparamagnetic character of our particles, we further prove the existence of a population of surviving aggregates able to maintain their integrity after switching off the external magnetic field. Finally, we suggest a schematic interaction scenario to rationalize the observed coexistence between reversible and irreversible aggregation.

In vivo long-term magnetic resonance imaging activity of ferritin-based magnetic nanoparticles versus a standard contrast agent.

New long-circulating maghemite nanoparticles of 4 and 6 nm, coated with an apoferritin protein capsid, exhibit useful properties to act as magnetic resonance imaging (MRI) contrast agents. A full in vivo study of the so-called apomaghemites reveals that their long-term MRI properties are better than those of a standard superparamagnetic iron oxide (SPIO) widely used in biomedical applications. The biodistribution of apomaghemites and standard SPIO was investigated by MRI in mice at two different concentrations, 6 and 2.5 mg of Fe·kg(-1), over 60 days. Significant differences are found at low dose (2.5 mg of Fe·kg(-1)). Thus, whereas apomaghemites are active for MR bioimaging of liver for 45 days, standard SPIO is not effective beyond 7 days. On the basis of our data, we may concluded that apomaghemites can act as new long-term MRI liver contrast agents, allowing first the diagnosis of a liver pathology and then monitoring after treatment without the need for a second injection.

Suspensions of repulsive colloidal particles near the glass transition: Time and frequency domain descriptions.

We study the relaxation of both spontaneous and shear-induced fluctuations in suspensions of charged-stabilized colloidal particles near the glass transition by dynamic light scattering and rheology. Both observations are here understood in terms of a common structural relaxation process under a hard-sphere mode-coupling formalism. For ergodic systems, we show that the descriptions of the relaxation dynamics in time and frequency domains are governed by a common set of dynamic parameters. It is further shown that the microscopic ergodicity break-up induces the emergence of the macroscopic glass elasticity.

Nondiffusive Brownian motion of deformable particles: breakdown of the "long-time tail".

We study the nondiffusive Brownian motion of both rigid and deformable mesoscopic particles by cross-correlated dynamic light scattering with microsecond temporal resolution. Whereas rigid particles show the classical long-time tail prediction, the transition to diffusive motion of deformable particles presents a striking behavior not explained by the existing hydrodynamic treatments. This observation can be interpreted in terms of a damped oscillatory deformational motion on time scales of the order of the Brownian time. Finally, we show that the nondiffusive Brownian motion depends on the specific flexibility of the particles.

Stochastic description of the light scattered by a polydisperse colloidal suspension: simulation and experiment.

In this work, the stochastic properties of the detected signal in dynamic light scattering experiments are examined in light of Doob's theorem. For Markovian observations of the Brownian particle position, we prove from this theorem that the electric field scattered by a polydisperse suspension can be accounted for by a linear combination of Ornstein-Uhlenbeck processes. A new algorithm for generating the fluctuating field scattered by a polydisperse system is proposed from this alternative formalism. The statistics of our synthetic data is compared satisfactorily with that resulting from the experimental signal scattered by a binary suspension of polystyrene microspheres.

Surface fractals in liposome aggregation.

In this work, the aggregation of charged liposomes induced by magnesium is investigated. Static and dynamic light scattering, Fourier-transform infrared spectroscopy, and cryotransmission electron microscopy are used as experimental techniques. In particular, multiple intracluster scattering is reduced to a negligible amount using a cross-correlation light scattering scheme. The analysis of the cluster structure, probed by means of static light scattering, reveals an evolution from surface fractals to mass fractals with increasing magnesium concentration. Cryotransmission electron microscopy micrographs of the aggregates are consistent with this interpretation. In addition, a comparative analysis of these results with those previously reported in the presence of calcium suggests that the different hydration energy between lipid vesicles when these divalent cations are present plays a fundamental role in the cluster morphology. This suggestion is also supported by infrared spectroscopy data. The kinetics of the aggregation processes is also analyzed through the time evolution of the mean diffusion coefficient of the aggregates.

Growth of lipid vesicle structures: from surface fractals to mass fractals.

We study fractal vesicle aggregates whose morphology is conditioned by the interaction between the lipid vesicle membranes and calcium and magnesium ions. These morphologies are probed by means of static light scattering using a cross-correlation scheme that avoids the multiple intracluster scattering. In contrast to the branched structures induced by calcium, we report a singular surface- to mass-fractal transition controlled by the magnesium concentration. From infrared spectroscopy data we conclude that the specific dehydration of the lipid membranes due to these cations plays an essential role in short-range intervesicle interactions.

Preparation and characterization of extruded magnetoliposomes.

Phospholipid vesicles encapsulating magnetic nanoparticles (here after called magnetoliposomes) have been prepared for targeting a drug to a specific organ using a magnetic force, as well as for local hyperthermia therapy. Magnetoliposomes are also an ideal platform for use as contrast agents. We describe the preparation and characterization of liposomes containing magnetite, a ferrimagnetic material. These liposomes were obtained by extrusion. To prevent the aggregation of particles, the magnetite was treated--prior to encapsulation--with a surfactant, resulting in a stable ferrofluid suspension. Once the ferrofluid had been obtained, it was used to hydrate the phospholipid layers. Magnetoliposomes had a diameter of around 200 nm, the same pore size as the membranes used for the extrusion. The encapsulation efficiency was dependent on the initial amount of ferrofluid present at the encapsulation stage, and in the worst case was 19%. This value corresponded to 82.06 mmol of magnetite per mole of phospholipid. Although we have used a determined membrane pore to obtain the magnetoliposomes, the method described here allows to prepare magnetoliposomes of different sizes as well as of different magnetite content.

Aggregation of liposomes induced by calcium: a structural and kinetic study.

In this work, the calcium-induced aggregation of phosphatidylserine liposomes is probed by means of the analysis of the kinetics of such process as well as the aggregate morphology. This novel characterization of liposome aggregation involves the use of static and dynamic light-scattering techniques to obtain kinetic exponents and fractal dimensions. For salt concentrations larger than 5mM, a diffusion-limited aggregation regime is observed and the Brownian kernel properly describes the time evolution of the diffusion coefficient. For slow kinetics, a slightly modified multiple contact kernel is required. In any case, a time evolution model based on the numerical resolution of Smoluchowski's equation is proposed in order to establish a theoretical description for the aggregating system. Such a model provides an alternative procedure to determine the dimerization constant, which might supply valuable information about interaction mechanisms between phospholipid vesicles.

The aggregation behaviour of protein-coated particles: a light scattering study.

The different mechanisms involved in the aggregation of spherical latex particles coated with bovine serum albumin (BSA) have been studied using static and dynamic light scattering. These techniques assess the fractal dimension of the aggregates and their mean hydrodynamic radius. Particles with different degrees of surface coverage have been prepared. The net charge of the covered particles has been modified by varying the pH of the aqueous phase. The aggregation rate was measured and used to determine the importance of the different aggregation mechanisms that are responsible for these types of flocculation processes. At low and intermediate degrees of surface coverage, bridging flocculation is the principal aggregation mechanism irrespective of the electrical state of the protein-particle complexes. At high degree of surface coverage, however, weak flocculation is important only when the BSA molecules are at their isoelectric point.