Christophe Travelet

Formation and Self-Organization Kinetics of α-CD/PEO-Based Pseudo-Polyrotaxanes in Water. A Specific Behavior at 30 °C†

alpha-Cyclodextrins (alpha-CDs) have the ability to form inclusion complexes with poly(ethylene oxide) (PEO) polymer chains. These pseudo-polyrotaxanes (PPRs) can be obtained by quenching an alpha-CD/PEO mixture in water from 70 degrees C down to a lower temperature (typically in the range from 5 to 30 degrees C) thanks to favorable interactions between alpha-CD cavities and PEO chains. Moreover, starting from a liquid alpha-CD/PEO mixture at a total mass fraction of 15% w/w at 70 degrees C, the formation of PPRs with time at a lower temperature induces a white physical gel with time, and phase separation is observed. We established that PPR molecules are exclusively found in the precipitated phase although unthreaded alpha-CD molecules and unthreaded PEO chains are in the liquid phase. At 30 degrees C, the physical gel formation is much slower than at 5 degrees C. At 30 degrees C, we established that, in a first step, alpha-CDs thread onto PEO chains, forming PPR molecules which are not in good solvent conditions in water. At a higher length scale, rapid aggregation of the PPR molecules occurs, and threaded alpha-CD-based nanocylinders form (cylinder length L = 5.7 nm and cylinder radius R = 4.7 nm). At a higher length scale, alpha-CD-based nanocylinders associate in a Gaussian way, engendering the formation of precipitated domains which are responsible for the high turbidity of the studied system. At the end of this first step (i.e., after 20 min), the system still remains liquid and the PPRs are totally formed. Then, in a second step (i.e., after 150 min), the system undergoes its reorganization characterized by a compacity increase of the precipitated domains and forms a physical gel. We found that PPRs are totally formed after 20 min at 30 degrees C and that the system stays in a nongel state up to 150 min. This opens new perspectives regarding the PPR chemical modification: between these two characteristic times, we can easily envisage an efficient chemical modification of the PPR molecules in water, as for instance an end-capping reaction leading to the synthesis of polyrotaxanes.

Self-Assembly of Amphiphilic Glycoconjugates into Lectin-Adhesive Nanoparticles

This work describes the synthesis and self-assembly of carbohydrate-clicked rod-coil amphiphilic systems. Copper-catalyzed Huisgen cycloaddition was efficiently employed to functionalize the hydrophilic extremity of PEG-b-tetra(p-phenylene) conjugates by lactose and N-acetyl-glucosamine ligands. The resulting amphiphilic systems spontaneously self-assembled into nanoparticles when dissolved in aqueous media, as evidenced by dynamic light scattering (DLS), transmission electron microscopy (TEM), and small-angle X-ray scattering (SAXS). The formation of highly monodisperse micelles having a mean diameter of 10 nm was observed for systems containing a PEG 900 core, and a decrease in the hydrophilic moiety (PEG 600) led to the formation of vesicles with a broader size distribution. The presence of carbohydrate residues on the surfaces of the micelles and their ability to establish specific interactions with wheat germ agglutinin (WGA) and peanut agglutinin (PNA) were further highlighted by light-scattering measurements, thus confirming the attractive applications of such sugar micelles in biosensor devices.

Glycopolymers as Antiadhesives of E. coli Strains Inducing Inflammatory Bowel Diseases

n-Heptyl α-d-mannose (HM) is a nanomolar antagonist of FimH, a virulence factor of E. coli. Herein we report on the construction of multivalent HM-based glycopolymers as potent antiadhesives of type 1 piliated E. coli. We investigate glycopolymer/FimH and glycopolymer/bacteria interactions and show that HM-based glycopolymers efficiently inhibit bacterial adhesion and disrupt established cell-bacteria interactions in vitro at very low concentration (0.1 μM on a mannose unit basis). On a valency-corrected basis, HM-based glycopolymers are, respectively, 10(2) and 10(6) times more potent than HM and d-mannose for their capacity to disrupt the binding of adherent-invasive E. coli to T84 intestinal epithelial cells. Finally, we demonstrate that the antiadhesive capacities of HM-based glycopolymers are preserved ex vivo in the colonic loop of a transgenic mouse model of Crohns disease. All together, these results underline the promising scope of HM-based macromolecular ligands for the antiadhesive treatment of E. coli induced inflammatory bowel diseases.

Multiblock copolymer behaviour of α-CD/PEO-based polyrotaxanes: towards nano-cylinder self-organization of α-CDs

The present work demonstrates that α-cyclodextrin/poly(ethylene oxide) (α-CD/PEO)-based polyrotaxanes (PRs) behave as multiblock copolymers. One block type consists of a rod-like tube made of 6 to 7 weakly stacked α-CDs threaded along the PEO chain. The other one is made of a naked PEO segment, i.e. the PR part that is not covered by α-CDs. This multiblock behaviour induces the self-organization of PRs in concentrated solution in dimethyl sulfoxide (DMSO) at room temperature leading to the formation of nano-cylinders. These nano-cylinders consist of assemblies of roughly 60 α-CD rod-like tubes through hydrogen bonding. Moreover, crystallites of naked PEO segments are formed since PEO is in poor solvent conditions (DMSO) at room temperature. Furthermore, the formation of α-CD nano-cylinders as well as of naked PEO segment crystallites leads to physical gelation of PRs in DMSO.

Self-assembly of maltoheptaose-block-polystyrene into micellar nanoparticles and encapsulation of gold nanoparticles.

The present paper discusses the controlled self-assembly of sugar-containing block copolymer, maltoheptaose-block-polystyrene (MH(1.2k)-b-PS(4.5k)), into micellar nanoparticles of ca. 30 nm radius in aqueous media and their possibility of gold encapsulation. Micellar association of MH(1.2k)-b-PS(4.5k) into nanoparticles was demonstrated by mixing a large amount of water (MH-selective solvent) with a solution of MH(1.2k)-b-PS(4.5k) in a mixture of tetrahydrofuran (THF) (PS-selective solvent) and water with a certain weight fraction [4:1 (w/w) THF/water], where MH(1.2k)-b-PS(4.5k) exists as well-swollen single chains, followed by evaporation of THF. The mean hydrodynamic radii (Rh) of the nanoparticles were determined by dynamic light scattering (DLS) to be ca. 30 and 80 nm depending upon the method of preparation. The resulting nanoparticles were clearly visualized by transmission electron microscopy (TEM), atomic force microscopy (AFM), and field emission gun-scanning electron microscopy (FEG-SEM) imaging and complemented by nanoparticle tracking analysis (NTA) using a NanoSight instrument. The preliminary study of the self-assembly of MH(1.2k)-b-PS(4.5k) in the presence of gold nanoparticles functionalized with PS chains grafted on their surface indicated potential possibilities of encapsulation of gold nanoparticles into the block copolymer nanoparticles in aqueous media.

Fluorescent Vesicles Consisting of Galactose‐based Amphiphilic Copolymers with a π‐Conjugated Sequence Self‐assembled in Water

Fluorescent vesicles considered as a mimic of natural primitive cells are prepared from poly(3-hexylthiophene)-block-poly(3-O-methacryloyl-D-galactopyranose) P3HT-b-PMAGP copolymers. The unique characteristic of such vesicular nanostructures is their architecture, which comprises a hydrophobic π-conjugated P3HT wall stabilized by a hydrophilic PMAGP interface featuring glucose units. The results of this work offer a very efficient and straightforward method for engineering well-controlled fluorescent nanoparticles (without the addition of dyes), which provide an excellent support to the study of carbohydrate-protein interactions.

Synthesis and self-assembly of amphiphilic polymers based on polyoxazoline and vegetable oil derivatives

The synthesis and self-assembly of amphiphilic polymers based on unsaturated vegetable oils and poly(2-methyl-2-oxazoline) (POx) are reported. Two architectures of lipopolymers were explored starting from fatty methyl esters and raw vegetable oils. The latter were converted into macroinitiators for cationic ring-opening polymerization (CROP) of 2-methyl-2-oxazoline. Firstly, a thiol–ene coupling reaction in the presence of mercaptoethanol under UV irradiation was performed to introduce hydroxyl groups that were further transformed into initiating species used for cationic polymerization. According to this strategy, various lipopoly(2-methyl-2-oxazoline)s (LipoPOxs) with different lipidic/POx ratios were successfully obtained and characterized by 1H NMR, SEC and MALDI-TOF analyses. Finally, the self-organization of the LipoPOx was studied using dynamic light scattering (DLS). Well-shaped nanoparticles were obtained with characteristic radii of 4.3 and 10.2 nm for the fatty ester- and triglyceride-based lipopolymers, respectively. The latter value is about twice the former one due to the higher lipidic fraction of the triglyceride-based polymer that promotes hydrophobic interactions. The relaxation time distributions of both systems were found to be monomodal, indicating monodisperse colloidal suspensions.

Tunable Aggregation and Gelation of Thermoresponsive Suspensions of Polymer-Grafted Cellulose Nanocrystals.

The colloidal stability together with the tunable aggregation and viscoelastic properties of thermoresponsive polymer-grafted cellulose nanocrystals (CNCs) were investigated. TEMPO oxidation of CNCs followed by peptidic coupling in water were used to covalently graft thermosensitive Jeffamine polyetheramine M2005 chains onto the surface of CNCs. The resulting polymer-decorated particles (M2005-g-CNCs) exhibited new colloidal properties, by their ability to perfectly redisperse in water and organic solvents such as toluene, dichloromethane or DMF after freeze-drying. In addition, they presented an enhanced thermal stability when compared to that of sulfated or TEMPO-oxidized CNCs. Dynamic light scattering experiments were used to demonstrate that the thermally induced aggregation of M2005-g-CNCs was fully reversible and reproducible over many temperature cycles and that, most interestingly, the aggregation number could be tuned by varying the ionic strength and/or the pH of the medium, making the suspension multiresponsive. This property arises from the variations of the sign (attractive or repulsive) and the range of the different types (entropic, electrostatic, hydrophobic) of interaction forces between the thermosensitive polymer-decorated nanoparticles. The variation of the viscoelastic properties of M2005-g-CNCs suspensions as a function of temperature, probed by oscillatory rheology measurements of more concentrated suspensions, revealed a reversible temperature-triggered liquid-to-gel transition. Such enhanced functionalities pave the way to the design of advanced CNC-based materials benefiting both from the intrinsic characteristics of these biosourced particles and the new properties imparted by the stimuli-sensitive grafted chains.

Photodimerization as an alternative to photocrosslinking of nanoparticles: proof of concept with amphiphilic linear polyoxazoline bearing coumarin unit

Photosensitive amphiphilic linear polyoxazolines (CoumC11–POxn) bearing alkyl chain decorated by a UV-active coumarin end group have been synthesized by cationic ring-opening polymerization (CROP). Using DLS and DOSY NMR experiments, their self-assemblies in water were compared with those of homologous photo-unreactive amphiphilic polyoxazolines (Cm–POxn). In both cases, spherical nanoparticles with DH-values around 10 nm were observed. The CoumC11–POxn nanoparticles were illuminated upon λ = 300 nm inducing the photo-dimerization of the coumarin units located in the inner compartment of the nanoparticles. Finally, the pros and the cons of the photo-dimerization of linear copolymers related to the photo-crosslinking of graft copolymers were discussed.

Synthesis, micellization and lectin binding of new glycosurfactants

Here we report the preparation and physico-chemical characterization of carbohydrate-decorated micelles and their interaction with lectins. A library of biosourced amphiphiles was prepared by copper-catalyzed azide-alkyne cycloaddition (CuAAC) between alkynyl sugars (lactose, N-acetyl-D-glucosamine) and azido-functionalized poly(ethylene glycol) esters (N3-PEG900-decanoate (C10) and -dodecanoate (C12)). In water, these glycoconjugates self-assemble into micelles of homogeneous nanometric size (11 nm) as evidenced by scattering techniques (DLS for light, and SAXS for X-ray). A comparative study with previously synthesized octadecanoate counterparts pointed out that that nature of the fatty acid has no significant influence on the particle size but only affects their compactness. These findings are in favor of a possible bulk preparation from lipid mixtures such as those encountered in renewable vegetable oils. The presence of the carbohydrate epitopes on the surface of the micelles and their bioavailability for lectin targeting were also evidenced by light scattering measurements using wheat germ agglutinin (WGA) and peanut (Arachis hypogaea) (PNA) lectins, supporting possible application as targeted drug nanocarriers.