Iron-based hybrid polyionic complexes as chemical reservoirs for the pH-triggered synthesis of Prussian blue nanoparticles.

HYPOTHESIS: Hybrid polyion complexes (HPICs) obtained from the complexation in aqueous solution of a double hydrophilic block copolymer and metal ions can act as efficient precursors for the controlled synthesis of nanoparticles. In particular, the possibility to control the availability of metal ions by playing on the pH conditions is of special interest to obtain nanoparticles with controlled size and composition. EXPERIMENTS: HPICs based on Fe3+ ions were used to initiate the formation of Prussian blue (PB) nanoparticles in presence of potassium ferrocyanide in reaction media with varying pH values. FINDINGS: Complexed Fe3+ ions within HPICs can be easily released by adjusting the pH value either through the addition of a base/acid or by using a merocyanine photoacid. This allows to modulate the reactivity of Fe3+ ions with potassium ferrocyanide present in solution. As a result, PB nanoparticles with different structures (core, core-shell), composition and controlled size are obtained.

Assemblies of poly(N-vinyl-2-pyrrolidone)-based double hydrophilic block copolymers triggered by lanthanide ions: characterization and evaluation of their properties as MRI contrast agents.

Because of the formation of specific antibodies to poly(ethylene glycol) (PEG) leading to life-threatening side effects, there is an increasing need to develop alternatives to treatments and diagnostic methods based on PEGylated copolymers. Block copolymers comprising a poly(N-vinyl-2-pyrrolidone) (PVP) segment can be used for the design of such vectors without any PEG block. As an example, a poly(acrylic acid)-block-poly(N-vinyl-2-pyrrolidone) (PAA-b-PVP) copolymer with controlled composition and molar mass is synthesized by reversible addition-fragmentation chain transfer (RAFT) polymerization. Mixing this copolymer with lanthanide cations (Gd3+, Eu3+, Y3+) leads to the formation of hybrid polyion complexes with increased stability, preventing the lanthanide cytotoxicity and in vitro cell penetration. These new nanocarriers exhibit enhanced T1 MRI contrast, when intravenously administered into mice. No leaching of gadolinium ions is detected from such hybrid complexes.

Double-hydrophilic block copolymer-metal ion associations: Structures, properties and applications.

Hybrid polyionic complexes (HPICs), constructed from double-hydrophilic block copolymers and metal ions, have been largely developed with increasing interest in the past decade in the fields of catalysis, materials science and biological applications. The chemical natures of both blocks are very versatile, but one block should be able to interact with ions, and the second one should be neutral. Many metals have been used to form HPICs, which have, in their simplest architectural form, a core-shell structure of a few tens of nanometers in radius with an external shell made of the neutral block of the copolymer. In this review, we focus our discussion on the stability, shape, size and inner structure of these hybrid micelles. We then describe the most recent applications of HPICs, as reported in the literature, and point out the current challenges, missing structural information and future perspectives for this class of organized structures.

Hybrid polymeric micelles stabilized by gallium ions: Structural investigation.

The addition of gallium ions to a solution of a double-hydrophilic block copolymer, i.e. poly(ethylene oxide)-block-poly(acrylic acid), leads to the spontaneous formation of highly monodisperse micelles with a Hybrid PolyIon Complexes (HPICs) core. By combining several techniques, a precise description of the HPIC architecture was achieved. In particular and for the first time, NMR and anomalous small angle X-ray scattering (ASAXS) enable tracking of the inorganic ions in solution and highlighting the co-localization of the gallium and the poly(acrylic acid) blocks in a rigid structure at the core of the micelle. Such a core has a radius of ca 4.3 nm while the complete nano-object with its poly(ethylene oxide) shell has a total radius of ca 11 nm. The aggregation number was also estimated using the ASAXS results. This comprehensive structural characterization of the Ga HPICs corroborates the assumptions made for HPICs based on other inorganic ions and demonstrates the universality of the HPIC structure leading, for example, to new families of contrast agents in medical imaging.

Effect of the microstructure of n-butyl acrylate/N-isopropylacrylamide copolymers on their thermo-responsiveness, self-organization and gel properties in water.

HYPOTHESIS: Polymer composition, microstructure, molar mass, architecture… critically affect the properties of thermoresponsive polymers in aqueous media. EXPERIMENTS: The behaviour of n-isopropylacrylamide and n-butyl acrylate-based copolymers of variable composition and structure (statistical, diblock or triblock) was studied in solution at different temperatures and concentrations with turbidimetry measurements, differential scanning calorimetry, electronic microscopy, rheology and scattering experiments. FINDINGS: This study illustrates how it is possible through chemical engineering of the microstructure of amphiphilic thermoresponsive polymers to modulate significantly the self-assembly, morphological and mechanical properties of these materials in aqueous media. Statistical structures induced a strong decrease of cloud point temperature compared to block structures with similar composition. Moreover, block structures lead below the transition temperature to the formation of colloidal structures. Above the transition temperature, the formation of colloidal aggregates is observed at low concentrations, and at higher concentrations the formation of gels. Neutron scattering and light scattering measurements show that for a given composition diblock structures lead to smaller colloids and mesoglobules than their triblock counterparts. Moreover, diblock structures, compared to triblock analogs, allow the formation of gels that do not demix with time (no synaeresis) but that are softer than triblock gels.

Frit inlet field-flow fractionation techniques for the characterization of polyion complex self-assemblies.

Polymer self-assemblies joining oppositely charged chains, known as polyion complexes (PICs), have been formed using poly(ethyleneoxide - b - acrylic acid)/poly(l-lysine), poly(ethyleneoxide-b-acrylic acid)/dendrigraft poly(l-lysine) and poly[(3-acrylamidopropyl) trimethylammonium chloride - b - N - isopropyl acrylamide]/poly(acrylic acid). The self-assemblies have been first characterized in batch by Dynamic Light Scattering. In a second step, their analysis by Flow Field-Flow Fractionation techniques (FlFFF) was examined. They were shown to be very sensitive to shearing, especially during the focus step of the fractionation, and this led to an incompatibility with asymmetrical FlFFF. On the other hand, Frit Inlet FlFFF proved to be very efficient to observe them, either in its symmetrical (FI-FlFFF) or asymmetrical version (FI-AsFlFFF). Conditions of elution were found to optimize the sample recovery in pure water. Spherical self-assemblies were detected, with a size range between 70-400nm depending on the polymers. Compared to batch DLS, FI-AsFlFFF clearly showed the presence of several populations in some cases. The influence of salt on poly(ethyleneoxide-b-acrylic acid) (PEO-PAA) 6000-3000/dendrigraft poly(l-lysine) (DGL 3) was also assessed in parallel in batch DLS and FI-AsFlFFF. Batch DLS revealed a first process of swelling of the self-assembly for low concentrations up to 0.8M followed by the dissociation. FI-AsFlFFF furthermore indicated a possible ejection of DGL3 from the PIC assembly for concentrations as low as 0.2M, which could not be observed in batch DLS.

Pickering emulsions: what are the main parameters determining the emulsion type and interfacial properties?

We synthesized surface-active lipophilic core-hydrophilic shell latex particles, and we probed their efficiency as emulsion stabilizers. The relative weight percentage of the shell, RS/P, was varied to trigger the balance between lipophilicity and hydrophilicity of the particles. Particle wettability could concomitantly be tuned by the pH of the aqueous phase determining the surface charge. Emulsions covering a wide range of RS/P and pH values were fabricated, and their type, oil-in-water (O/W) or water-in-oil (W/O), and kinetic stability were systematically assessed. By adapting the particle gel trapping technique to pH-variable systems and by exploiting the limited coalescence process, we were able to determine the proportion of oil/water interfacial area, C, covered by the particles as well as their contact angle, θ. All of these data were gathered into a single generic diagram showing good correlation between the emulsion type and the particle contact angle (O/W for θ < 90° and W/O for θ > 90°) in agreement with the empirical Finkle rule. Interestingly, no stable emulsion could be obtained when the wettability was nearly balanced and a "bipolar"-like behavior was observed, with the particles adopting two different contact angles whose average value was close to 90°. For particles such that θ < 90°, O/W emulsions were obtained, and, depending on the pH of the continuous phase, the same type of particles and the same emulsification process led to emulsions characterized either by large drops densely covered by the particles or by small droplets that were weakly covered. The two metastable states were also accessible to emulsions stabilized by particles of variable origins and morphologies, thus proving the generality of our findings.

Investigation of the reversibility of the unimer-to-aggregate transition in block copolymers by surface tension-measurements.

Two DNA-block copolymers, poly(caprolactone)-DNA and poly(methyl metacrylate)-DNA, were synthesized by conjugation of a short single strand of DNA (12 or 22mer) to a single reactive group at one end of the synthetic polymer. These polymers self-assemble in water, without the need of any cosolvent, forming micelle-like aggregates that were imaged by TEM. The solution behavior of the bioconjugated polymers was investigated by surface tension measurements. In the direction of dilution, the surface tension was measured using a down-scaled Wilhelmy plate method. To proceed in the reverse direction (concentration), we measured the surface tension of a sessile drop during its evaporation. This latter method was firstly validated using ionic and non-ionic surfactants, including polymeric surfactants. It was then applied to investigate the unimer to micelles transition of the DNA-block copolymers. In all cases, a reversible transition was observed demonstrating the existence of a critical micellar concentration, close to 0.01 mmol L(-1) for all the conjugates. The CMC was only slightly influenced by the length of the hydrophilic DNA block.

Biphenyl bicelle disks align perpendicular to magnetic fields on large temperature scales: a study combining synthesis, solid-state NMR, TEM, and SAXS.

A phosphatidylcholine lipid (PC) containing a biphenyl group in one of its acyl chains (1-tetradecanoyl-2-(4-(4-biphenyl)butanoyl)-sn-glycero-3-PC, TBBPC) was successfully synthesized with high yield. Water mixtures of TBBPC with a short-chain C(6) lipid, dicaproyl-PC (DCPC), lead to bicelle systems formation. Freeze-fracture electron microscopy evidenced the presence of flat bilayered disks of 800 A diameter for adequate composition, hydration, and temperature conditions. Because of the presence of the biphenyl group, which confers to the molecule a positive magnetic anisotropy Delta chi, the disks align with their normal, n, parallel to the magnetic field B(0), as directly detected by (31)P, (14)N, (2)H solid-state NMR and also using small-angle x-ray scattering after annealing in the field. Temperature-composition and temperature-hydration diagrams were established. Domains where disks of TBBPC/DCPC align with their normal parallel to the field were compared to chain-saturated lipid bicelles made of DMPC(dimyristoylPC)/DCPC, which orient with their normal perpendicular to B(0). TBBPC/DCPC bicelles exist on a narrow range of long- versus short-chain lipid ratios (3%) but over a large temperature span around room temperature (10-75 degrees C), whereas DMPC/DCPC bicelles exhibit the reverse situation, i.e., large compositional range (22%) and narrow temperature span (25-45 degrees C). The two types of bicelles present orienting properties up to 95% dilution but with the peculiarity that water trapped in biphenyl bicelles exhibits ordering properties twice as large as those observed in the saturated-chains analog, which offers very interesting properties for structural studies on hydrophilic or hydrophobic embedded biomolecules.

Bicelle membranes and their use for hydrophobic peptide studies by circular dichroism and solid state NMR.

Mixtures of dicaproyl- (DC), dimyristoyl- (DM) and 1-tetradecanoyl-2-biphenylbutanoyl-(TBB) phosphatidylcholine (PC) in water produce bicelle membranes that are oriented by magnetic fields. DMPC/DCPC systems orient such that their membrane plane is parallel to the magnetic field, whereas for TBBPC/DCPC, the plane is perpendicular to the field. Partial temperature-composition-hydration diagrams are established using solid-state 31P-NMR. DMPC/DCPC bicelles exist on a large range of composition but on a narrow temperature domain (25-45 degrees C). At converse, TBBPC/DCPC form bicelles on a narrow compositional range but over a large temperature span (10-70 degrees C). The TBBPC/DCPC bicelles are shown to be a very powerful potential tool to study the orientation of hydrophobic helices in membranes using wide line 15N-NMR. The DMPC/DCPC system that undergoes a micelle-to-bicelle transition on going from 10 degrees C to 40 degrees C may be used with circular dichroism to study the state of association of hydrophobic helices within the membrane. Results suggest that the transmembrane fragment of the neu/erbB-2 receptor is monomeric in micellar medium and dimeric/multimeric in bicelle membranes.