Stabilization Improves Theranostic Properties of Lipiodol®-Based Emulsion During Liver Trans-arterial Chemo-embolization in a VX2 Rabbit Model.

PURPOSE: To demonstrate that stability is a crucial parameter for theranostic properties of Lipiodol®-based emulsions during liver trans-arterial chemo-embolization. MATERIALS AND METHODS: We compared the theranostic properties of two emulsions made of Lipiodol® and doxorubicin in two successive animal experiments (One VX2 tumour implanted in the left liver lobe of 30 rabbits). Emulsion-1 reproduced one of the most common way of preparation (ratio of oil/water: 1/1), and emulsion-2 was designed to obtain a water-in-oil emulsion with enhanced stability (ratio of oil/water: 3/1, plus an emulsifier). The first animal experiment compared the tumour selectivity of the two emulsions: seven rabbits received left hepatic arterial infusion (HAI) of emulsion-1 and eight received HAI of emulsion-2. 3D-CBCT acquisitions were acquired after HAI of every 0.1 mL to measure the densities' ratios between the tumours and the left liver lobes. The second animal experiment compared the plasmatic and tumour doxorubicin concentrations after HAI of 1.5 mg of doxorubicin administered either alone (n = 3) or in emulsion-1 (n = 6) or in emulsion-2 (n = 6). RESULTS: Emulsion-2 resulted in densities' ratios between the tumours and the left liver lobes that were significantly higher compared to emulsion-1 (up to 0.4 mL infused). Plasmatic doxorubicin concentrations (at 5 min) were significantly lower after HAI of emulsion-2 (19.0 µg/L) than emulsion-1 (275.3 µg/L, p < 0.01) and doxorubicin alone (412.0 µg/L, p < 0.001), and tumour doxorubicin concentration (day-1) was significantly higher after HAI of emulsion-2 (20,957 ng/g) than in emulsion-1 (8093 ng/g, p < 0.05) and doxorubicin alone (2221 ng/g, p < 0.01). CONCLUSION: Stabilization of doxorubicin in a water-in-oil Lipiodol®-based emulsion results in better theranostic properties.

Hindered diffusion of MRI contrast agents in rat brain extracellular micro-environment assessed by acquisition of dynamic T1 and T2 maps.

The knowledge of brain tissues characteristics (such as extracellular space and tortuosity) represents valuable information for the design of optimal MR probes for specific biomarkers targeting. This work proposes a methodology based on dynamic acquisition of relaxation time maps to quantify in vivo MRI contrast agent concentration after intra-cerebral injection in rat brain. It was applied to estimate the hindered diffusion in brain tissues of five contrast agents with different hydrodynamic diameters (Dotarem(®) ≈ 1 nm, P846 ≈ 4 nm, P792 ≈ 7 nm, P904 ≈ 22 nm and Gd-based emulsion ≈ 170 nm). In vivo apparent diffusion coefficients were compared with those estimated in an obstacle-free medium to determine brain extracellular space and tortuosity. At a 2 h imaging timescale, all contrast agents except the Gd-based emulsion exhibited significant diffusion through brain tissues, with characteristic times compatible with MR molecular imaging (<70 min to diffuse between two capillaries). In conclusion, our experiments indicate that MRI contrast agents with sizes up to 22 nm can be used to perform molecular imaging on intra-cerebral biomarkers. Our quantification methodology allows a precise estimation of apparent diffusion coefficients, which is helpful to calibrate optimal timing between contrast agent injection and MRI observation for molecular imaging studies.

Measuring the kinetics of biomolecular recognition with magnetic colloids.

We introduce a general methodology based on magnetic colloids to study the recognition kinetics of tethered biomolecules. Access to the full kinetics of the reaction is provided by an explicit measure of the time evolution of the reactant densities. Binding between a single ligand and its complementary receptor is here limited by the colloidal rotational diffusion. It occurs within a binding distance that can be extracted by a reaction-diffusion theory that properly accounts for the rotational Brownian dynamics. Our reaction geometry allows us to probe a large diversity of bioadhesive molecules and tethers, thus providing a quantitative guidance for designing more efficient reactive biomimetic surfaces, as required for diagnostic, therapeutic, and tissue engineering techniques.

Acceleration of the recognition rate between grafted ligands and receptors with magnetic forces.

When ligands and receptors are both attached on surfaces, because of the restriction of configurational freedom, their recognition kinetics may be substantially reduced as compared with freely diffusing species. In nature, this reduction may influence the efficiency of the capture and adhesion of circulating cells. Here we show that similar consequences are observed for colloids grafted with biomolecules that are used as probes for diagnostics. We exploit Brownian magnetic colloids that self-assemble into linear chains to show also that the resulting one-dimensional confinement considerably accelerates the recognition rate between grafted receptors and their ligands. We propose that because confinement significantly augments the colliding frequency, it also causes a large increase in the attempt frequency of the recognition. This work gives the basis of a rapid, homogeneous, and highly sensitive bioanalysis method.

Observation of shear-induced nematic-isotropic transition in side-chain liquid crystal polymers.

Flow-induced phase transitions are a fundamental (but poorly understood) property of non-equilibrium systems, and are also of practical importance for tuning the processing conditions for plastics, petroleum products, and other related materials. Recognition that polymers may exhibit liquid crystal properties has led to the discovery of the first tailored side-chain liquid crystal polymers (SCLCPs), which are formed by inserting a spacer between the main polymer chain and the lateral mesogen liquid-crystalline graftings. Subsequent research has sought to understand the nature of the coupling between the main polymer chain and the mesogens, with a view to obtaining better control of the properties of these tailored structures. We show here that the parallel or perpendicular orientation of the mesogens with respect to the main chain can be reversed by the application of an external field produced by a shear flow, demonstrating the existence of an isotropic nematic phase transition in SCLCPs. Such a transition, which was theoretically predicted for low-molecular-weight liquid crystals but never observed, is shown to be a general property of SCLCPs too. We expect that these SCLCPs will prove to be good candidate systems for the experimental study of these non-equilibrium phenomena.