Nicolas Sanson

Small and Stable Sulfobetaine Zwitterionic Quantum Dots for Functional Live-Cell Imaging

We have developed a novel surface coating for semiconductor quantum dots (QDs) based on a heterobifunctional ligand that overcomes most of the previous limits of these fluorescent probes in bioimaging applications. Here we show that QDs capped with bidentate zwitterionic dihydrolipoic acid-sulfobetaine (DHLA-SB) ligands are a favorable alternative to polyethylene glycol-coated nanoparticles since they combine small sizes, low nonspecific adsorption, preserved optical properties, and excellent stability over time and a wide range of pH and salinity. Additionally, these QDs can easily be functionalized with biomolecules such as streptavidin (SA) and biotin. We applied streptavidin-functionalized DHLA-SB QDs to track the intracellular recycling of cannabinoid receptor 1 (CB1R) in live cells. These QDs selectively recognized the pool of receptors at the cell surface via SA-biotin interactions with negligible nonspecific adsorption. The QDs retained their optical properties, allowing the internalization of CB1R into endosomes to be followed. Moreover, the cellular activity was apparently unaffected by the probe.

Synthesis of nanogels/microgels by conventional and controlled radical crosslinking copolymerization

This review compares conventional and controlled radical polymerization techniques and processes in preparing nano-/microgels. Special focus is made on the synthetic parameters that allow controlling their size, morphology, composition, and structural homogeneity.

Study of poly(N,N-diethylacrylamide) nanogel formation by aqueous dispersion polymerization of N,N-diethylacrylamide in the presence of poly(ethylene oxide)-b-poly(N,N-dimethylacrylamide) amphiphilic macromolecular RAFT agents

The formation of thermoresponsive poly(N,N-diethylacrylamide) (PDEAAm) nanogels via an aqueous dispersion polymerization process in the presence of poly(ethylene oxide)-b-poly(N,N-dimethylacrylamide) macromolecular reversible addition–fragmentation chain transfer agents (macroRAFT agents) was studied. The latter exhibit a hydrophobic trithiocarbonate reactive group with a dodecyl substituent, and had previously proved to act simultaneously as control agents and stabilizers in such a synthesis process (Rieger et al., J. Polym. Sci. Part A: Polym. Chem., 2009, 47, 2373). The nanogel size and stability were found to depend strongly on the chain length of the macroRAFT agents, but also on the crosslinker (N,N′-methylene bisacrylamide) and monomer concentrations. The aim of the present work was to better understand the mechanisms that govern the nanogel formation in such heterogeneous polymerization conditions performed under RAFT control, with special emphasis on the role of the macroRAFT agents. In the first part, the aqueous solution properties of the macroRAFT agents in the conditions of the dispersion polymerizations were studied by light scattering and fluorescence spectroscopy and it was found that they self-assemble to form star micelles. In the second part, the nanogel formation at different DEAAm and crosslinker concentrations was monitored by dynamic and static light scattering, and by size exclusion chromatography. It appeared that at low monomer conversion the calculated number of chains per nanogel particle was close to the aggregation number, Nagg, of the macroRAFT agent micelles. With increasing conversions, however, the number of chains clearly increased and exceeded the initial Nagg. Higher monomer concentrations hardly influenced the formation process and thus the gel particle size, whereas enhanced crosslinker concentration had a strong impact on the latter. These results strongly suggest that precursor particles are formed very rapidly at the polymerization onset and then aggregate with each other to form complex inter-crosslinked particles.

Poly(N-isopropylacrylamide) microgels at the oil-water interface: interfacial properties as a function of temperature.

Highly monodisperse poly(N-isopropylacrylamide), PNiPAM, microgels were prepared by the conventional radical polymerization of NiPAM in the presence of dimethylamino ethyl methacrylate (DMAEMA) monomers at various concentrations. The effect of DMAEMA on the polymerization of PNiPAM microgels was examined at constant initiator (V50) and cross-linker (MBA) concentrations. The presence of DMAEMA in the synthesis batch allows for the preparation of PNiPAM microgels with controlled size and a narrow size distribution. The oil(dodecane)/water interfacial properties of the model PNiPAM microgels were then investigated. The pendant drop technique was used to measure the interfacial tensions as a function of temperature. Over the whole range of temperature (20-45 degrees C), the interfacial tension remains low (on the order of 17 mN/m) and goes through a minimum (12 mN/m) at a temperature of about 34 degrees C, which well matches the volume phase transition temperature (VPTT) of PNiPAM microgels. Below the VPTT, the decrease in the interfacial tension with temperature is likely to be due to the adsorption of dense layers because of the decrease of the excluded volume interactions. Above the VPTT, we suggest that the increase in the interfacial tension with temperature comes from the adsorption of loosely packed PNiPAM microgels. We also studied the effect of temperature on the stability of emulsions. Dodecane in water emulsions, which form at ambient temperature, are destabilized as the temperature exceeds the VPTT. In light of the interfacial tension results, we suggest that emulsion destabilization arises from the adsorption of aggregates above the VPTT and not from an important desorption of microgels. Aggregate adsorption would bring a sufficiently high number of dodecane molecules into contact with water to induce coalescence without changing the interfacial tension very much.

Hydrophilic block copolymer-directed growth of lanthanum hydroxide nanoparticles

Stable hairy lanthanum hydroxide nanoparticles were synthesized in water by performing hydrolysis and condensation reactions of lanthanum cations in the presence of double hydrophilic polyacrylic acid-b-polyacrylamide block copolymers (PAA-b-PAM). In the first step, the addition of asymmetric PAA-b-PAM copolymers (Mw,PAA < Mw,PAM) to lanthanum salt solutions, both at pH = 5.5, induces the formation of monodispersed micellar aggregates, which are predominantly isotropic. The core of the hybrid aggregates is constituted of a lanthanum polyacrylate complex whose formation is due to bidentate coordination bonding between La3+ and acrylate groups, as shown by ATR-FTIR experiments and pH measurements. The size of the micellar aggregates depends on the molecular weight of the copolymer but is independent of the copolymer to metal ratio in solution. In the second step, the hydrolysis of lanthanum ions is induced by addition of a strong base such as sodium hydroxide. Either flocculated suspensions or stable anisotropic or spherical nanoparticles of lanthanum hydrolysis products were obtained depending on the metal complexation ratio [acrylate]/[La]. The variation of that parameter also enables the control of the size of the core-corona nanoparticles obtained by lanthanum hydroxylation. The asymmetry degree of the copolymer was shown to influence both the size and the shape of the particles. Elongated particles with a high aspect ratio, up to 10, were obtained with very asymmetric copolymers (Mw,PAM/Mw,PAA ≥ 10) while shorter rice grain-like particles were obtained with a less asymmetric copolymer. The asymmetry degree also influences the value of the critical metal complexation degree required to obtain stable colloidal suspensions of polymer-stabilized lanthanum hydroxide.

Tracking the interfacial dynamics of PNiPAM soft microgels particles adsorbed at the air-water interface and in thin liquid films

We report the behavior of thermosensitive soft microgel particles adsorbed at the air–water interface. We study the effect of temperature on the adsorption, interfacial diffusion, and surface rheology of pure N-isopropylacrylamide (NiPAM) microgel particles at the air–water interface. We find that the surface tensions of the solutions are the same as those of polyNiPAM solution; hence, their adsorption properties are dominated by the surface activity of the NiPAM repeat units of the particles. Particle-tracking experiments show that the particles adsorb irreversibly at the interface and form stable clusters at very low concentrations, e.g., 5.10-3 wt%. We suggest that attractions between dangling arms or capillary interaction may be responsible for the formation of these clusters. For concentrations above 10-2 wt%, the interface is filled with particles, and their Brownian diffusivity is arrested. The compression elastic moduli—measured using the pendant drop method—are one or two orders of magnitude below those obtained for hard particles and NiPAM chains, and their value is probably dominated by the intrinsic compressibility of the particles. The thin liquid films made from microgels exhibit a symmetric drainage, consistent with a high surface viscosity, but their lifetime is surprisingly short, illustrating the fragility of the films. We observed the formation of a monolayer of microgels bridging the two interfaces of the film outside the dimple. This zone grows and thins over time to a point where the microgels are highly compressed and stretched, resulting in the rupture of the film.

Hybrid Polyion Complex Micelles Formed from Double Hydrophilic Block Copolymers and Multivalent Metal Ions: Size Control and Nanostructure

Hybrid polyion complex (HPIC) micelles are nanoaggregates obtained by complexation of multivalent metal ions by double hydrophilic block copolymers (DHBC). Solutions of DHBC such as the poly(acrylic acid)-block-poly(acrylamide) (PAA-b-PAM) or poly(acrylic acid)-block-poly(2-hydroxyethylacrylate) (PAA-b-PHEA), constituted of an ionizable complexing block and a neutral stabilizing block, were mixed with solutions of metal ions, which are either monoatomic ions or metal polycations, such as Al(3+), La(3+), or Al(13)(7+). The physicochemical properties of the HPIC micelles were investigated by small angle neutron scattering (SANS) and dynamic light scattering (DLS) as a function of the polymer block lengths and the nature of the cation. Mixtures of metal cations and asymmetric block copolymers with a complexing block smaller than the stabilizing block lead to the formation of stable colloidal HPIC micelles. The hydrodynamic radius of the HPIC micelles varies with the polymer molecular weight as M(0.6). In addition, the variation of R(h) of the HPIC micelle is stronger when the complexing block length is increased than when the neutral block length is increased. R(h) is highly sensitive to the polymer asymmetry degree (block weight ratio), and this is even more true when the polymer asymmetry degree goes down to values close to 3. SANS experiments reveal that HPIC micelles exhibit a well-defined core-corona nanostructure; the core is formed by the insoluble dense poly(acrylate)/metal cation complex, and the diffuse corona is constituted of swollen neutral polymer chains. The scattering curves were modeled by an analytical function of the form factor; the fitting parameters of the Pedersens model provide information on the core size, the corona thickness, and the aggregation number of the micelles. For a given metal ion, the micelle core radius increases as the PAA block length. The radius of gyration of the micelle is very close to the value of the core radius, while it varies very weakly with the neutral block length. Nevertheless, the radius of gyration of the micelle is highly dependent on the asymmetry degree of the polymer: if the neutral block length increases in a large extent, the micelle radius of gyration decreases due to a decrease of the micelle aggregation number. The variation of the R(g)/R(h) ratio as a function of the polymer block lengths confirms the nanostructure associating a dense spherical core and a diffuse corona. Finally, the high stability of HPIC micelles with increasing concentration is the result of the nature of the coordination complex bonds in the micelle core.

Tunable and Reversible Aggregation of Poly(ethylene oxide-st-propylene oxide) Grafted Gold Nanoparticles

Two amino-terminated amphiphilic copolymers, M600 and M1000, with different ethylene oxide to propylene oxide EO/PO ratios, 1/9 and 19/3, respectively, were coupled by thioctic acid, which allows an excellent affinity with gold surface. Then, amphiphilic thermally responsive gold nanoparticles (AuNPs) were prepared either by ligands exchange on precursor gold nanoparticles or by direct reduction of gold source in presence of stabilizing copolymers. The as-obtained AuNPs are monodisperse with a size varying from 2 to 17 nm depending on the synthesis used. The main parameters controlling the AuNPs assemblies were identified: the ethylene oxide to propylene oxide ratio in the polymer corona, the ionic strength of the solution, and the curvature of AuNPs. An interesting result is the possibility to tune the aggregation temperature from 8 to 15 degrees C of AuNPs coated by the same polymer only by changing the curvature of the AuNPs from 17 to 2 nm. This temperature change versus the curvature of the nanoparticle is ascribed to the decrease in hydration volume per hydrophilic group in the corona due to the change of the polymer chain conformation with changing the particle size. Moreover, one unique aggregation temperature between 12 and 60 degrees C can be also obtained by mixing copolymers with different EO/PO ratios. Then, the corona, constituted by a mixture of polymers, behaves as a corona composed by an average statistic copolymer with the intermediate composition.

Reversible Controlled Assembly of Thermosensitive Polymer-Coated Gold Nanoparticles

Aggregation of thermosensitive polymer-coated gold nanoparticles was performed in aqueous solution in the presence of a triblock copolymer poly(ethylene oxide)-block-poly(propylene oxide)-block-poly(ethylene oxide) (Pluronic P123, PEO(20)-PPO(68)-PEO(20)). The gold nanoparticles, AuNPs, which are covered by thermosensitive statistical copolymers poly(EO(x)-st-PO(y)), aggregate when the temperature is higher than the phase transition temperature of the polymer, leading to a macroscopic precipitation. The presence of Pluronic chains in solution prevents the uncontrolled aggregation of the AuNPs at higher temperature than both the aggregation temperature of the AuNPs (T(agg)) and the critical micellization temperature (cmt) of the Pluronic. The size, the colloidal stability, and the optical properties of the AuNPs aggregates are modulated as a function of the P123-to-AuNP ratio, which constitutes the critical parameter of the system. Moreover, the AuNP aggregation is totally reversible upon decreasing the temperature below T(agg). Our approach constitutes an easy way to the formation of well-controlled nanoparticle aggregates with well-defined sizes. The resulting aggregates have been characterized by UV-vis spectroscopy, dynamic light scattering, and electron microscopy.

Thermoresponsive Toughening with Crack Bifurcation in Phase‐Separated Hydrogels under Isochoric Conditions

A novel mode of gel toughening displaying crack bifurcation is highlighted in phase-separated hydrogels. By exploring original covalent network topologies, phase-separated gels under isochoric conditions demonstrate advanced thermoresponsive mechanical properties: excellent fatigue resistance, self-healing, and remarkable fracture energies. Beyond the phase-transition temperature, the fracture proceeds by a systematic crack-bifurcation process, unreported so far in gels.