Min-Hui Li

Stimuli-responsive polymer vesicles

Polymer vesicles, commonly called polymersomes, are spherical shell structures in which an aqueous compartment is enclosed by a bilayer membrane made from amphiphilic block copolymers. Compared to liposomes, their low molecular weight analogues, polymersomes have many superior properties (higher toughness, better stability, tailorable membrane properties), which make them attractive candidates for applications including encapsulation, drug delivery, nanoreactors and templates for micro- or nano-structured materials. Many potential applications require the ability to control the release of substances encapsulated in the interior compartment and/or in the hydrophobic core of membrane. To address this goal, polymersomes have to be developed in which a specific stimulus destabilises the vesicle structure. In this article we review the most promising approaches to make stimuli-responsive polymer vesicles that permit the controlled release of encapsulated contents. Stimuli including hydrolysis, oxidation, reduction, pH, temperature and light are discussed and their effect on the chemical and physical structure of the amphiphilic copolymers is also described.

Self-Assembly of Linear−Dendritic Diblock Copolymers: From Nanofibers to Polymersomes

We report the formation of cylindrical micelles, sheet-like micelles, tubular micelles, as well as polymer vesicles by a new series of amphiphilic linear-dendritic block-copolymers (BCs). The BCs, noted as PEGm-AZOn, are composed of poly(ethylene glycol) (PEG) chains of different molecular weights as hydrophilic blocks and the first four generations of azobenzene-containing dendrons based on 2,2-bis(hydroxymethyl)propionic acid (bis-MPA) as hydrophobic blocks (m represents the degree of polymerization of PEG, and n is the number of azobenzene units at the periphery of dendron). The polymeric aggregates were formed by adding water to solutions of the BCs in dioxane. The micellar dispersions in water were finally obtained by removing dioxane via dialysis against water. The morphology of the micellar self-assemblies was studied by transmission electron microscopy (TEM), cryo-electron microscopy (cryo-TEM), and atomic force microscopy (AFM). A generation-dependent aggregation behavior was found for the series of BCs PEG45-AZOn. Core-shell structured nanofibers with an inner diameter of 8 nm were observed for the copolymer PEG45-AZO2 (hydrophilic/hydrophobic weight ratio equal to 67/33). Lyotropic liquid crystalline behavior was detected for the aqueous solution of the nanofibers. The coexistence of sheet-like aggregates and tubular micelles was detected for the copolymer PEG45-AZO8 in which the number of cyanoazobenzene units is increased to 8 (hydrophilic/hydrophobic weight ratio equal to 33/67). The tubular micelles could be intermediates in the sheet-like aggregate-to-vesicle transition. Polymer vesicles (polymersomes) with a diameter in the range 300-800 nm were observed for the copolymer PEG45-AZO16 (hydrophilic/hydrophobic weight ratio equal to 20/80). The membrane of the sheet-like aggregates, tubular micelles, and polymersomes was shown to have a bilayer structure, as revealed by cryo-TEM. UV illumination of the aqueous polymersome dispersion induced the formation of wrinkles in the vesicle membrane, thus showing that this type of polymeric aggregate is photoresponsive.

Bursting of sensitive polymersomes induced by curling.

Polymersomes, which are stable and robust vesicles made of block copolymer amphiphiles, are good candidates for drug carriers or micro/nanoreactors. Polymer chemistry enables almost unlimited molecular design of responsive polymersomes whose degradation upon environmental changes has been used for the slow release of active species. Here, we propose a strategy to remotely trigger instantaneous polymersome bursting. We have designed asymmetric polymer vesicles, in which only one leaflet is composed of responsive polymers. In particular, this approach has been successfully achieved by using a UV-sensitive liquid-crystalline copolymer. We study experimentally and theoretically this bursting mechanism and show that it results from a spontaneous curvature of the membrane induced by the remote stimulus. The versatility of this mechanism should broaden the range of applications of polymersomes in fields such as drug delivery, cosmetics and material chemistry.

Artificial muscles based on liquid crystal elastomers.

This paper presents our results on liquid crystal (LC) elastomers as artificial muscle, based on the ideas proposed by de Gennes. In the theoretical model, the material consists of a repeated series of main-chain nematic LC polymer blocks, N, and conventional rubber blocks, R, based on the lamellar phase of a triblock copolymer RNR. The motor for the contraction is the reversible macromolecular shape change of the chain, from stretched to spherical, that occurs at the nematic-to-isotropic phase transition in the main-chain nematic LC polymers. We first developed a new kind of muscle-like material based on a network of side-on nematic LC homopolymers. Side-on LC polymers were used instead of main-chain LC polymers for synthetic reasons. The first example of these materials was thermo-responsive, with a typical contraction of around 35–45% and a generated force of around 210 kPa. Subsequently, a photo-responsive material was developed, with a fast photochemically induced contraction of around 20%, triggered by UV light. We then succeeded in preparing a thermo-responsive artificial muscle, RNR, with lamellar structure, using a side-on nematic LC polymer as N block. Micrometre-sized artificial muscles were also prepared. This paper illustrates the bottom-up design of stimuli-responsive materials, in which the overall material response reflects the individual macromolecular response, using LC polymer as building block.

Thermoresponsive self-assembled polymer colloids in water

Thermoresponsive polymer colloids made of amphiphilic block copolymers are reviewed in this paper. The main families of thermoresponsive polymers, including hydrophilic polymers with LCST (PEG, PNIPAM, poly(oxazoline)s and elastin-like polypeptides, etc.) and hydrophobic polymers with thermotropic phase transitions (liquid crystalline and crystalline polymers), are first described with the details of the underlying physical chemical principles. Polymer colloids with thermoresponsive polymers as the hydrophobic core, hydrophilic corona or both of them depending on temperature (schizophrenic systems) are discussed and their potential bio-related applications highlighted. We also take notice of the particular thermoresponsive properties of PEG in the polymer colloids. Hydrophilic PEG has its water solubility and degree of hydration decreased with increasing temperature in the range far below its LCST (∼100 °C). These properties can result in significant or even drastic morphological changes in colloids, which should be taken into account when designing thermoresponsive polymer colloids using the PEG corona.

Amphiphilic liquid-crystal block copolymer nanofibers via RAFT-mediated dispersion polymerization

Well-defined, cholesteryl-based, amphiphilic block copolymer nanofibers have been obtained in a simple, one-pot, ethanol/water dispersion polymerization process using poly((meth)acrylic acid-co-(poly(ethylene glycol) (meth)acrylate) copolymers end-functionalized by a reactive trithiocarbonate end-group as macromolecular reversible addition–fragmentation chain transfer agents (macroRAFT agents). The resulting highly concentrated dispersions were analyzed by TEM (transmission electron microscopy), cryo-TEM, SAXS (small angle X-ray scattering) and SANS (small angle neutron scattering), which allowed the shape and size of the nanoobjects formed in situ to be fully characterized and which revealed moreover the presence of a smectic order in the hydrophobic cores. Due to this particular substructure, the nanofiber organization was observed over a broad composition range of the amphiphilic block copolymers.

Reduction-Responsive Cholesterol-Based Block Copolymer Vesicles for Drug Delivery

We developed a new robust reduction-responsive polymersome based on the amphiphilic block copolymer PEG-SS-PAChol. The stability and robustness were achieved by the smectic physical cross-linking of cholesterol-containing liquid crystal polymer PAChol in the hydrophobic layer. The reduction-sensitivity was introduced by the disulfide bridge (-S-S-) that links the hydrophilic PEG block and the hydrophobic PAChol block. We used a versatile synthetic strategy based on atom transfer radical polymerization (ATRP) to synthesize the reduction-responsive amphiphilic block copolymers. The reductive cleavage of the disulfide bridge in the block copolymers was first evidenced in organic solution. The partial destruction of PEG-SS-PAChol polymersomes in the presence of a reducing agent was then demonstrated by cryo-electron microscopy. Finally, the calcein release from PEG-SS-PAChol polymersomes triggered by glutathione (GSH) was observed both in PBS suspension and in vitro inside the macrophage cells. High GSH concentrations (≥35 mM in PBS or artificially enhanced in macrophage cells by GSH-OEt pretreatment) and long incubation time (in the order of hours) were, however, necessary to get significant calcein release. These polymersomes could be used as drug carriers with very long circulation profiles and slow release kinetics.

Light-responsive wires from side-on liquid crystalline azo polymers

The pioneering work of Professor de Gennes in the field of liquid crystalline polymers and elastomers is outlined with an emphasis on artificial muscles. To illustrate the presentation, results on light-responsive nematic liquid crystalline elastomer fibres are reported. Two kinds of light-responsive wires were fabricated from an azobenzene-containing liquid crystalline copolymer with, or without cross-linking. Cross-linked wires were obtained by the reaction between the hydroxyl groups of the liquid crystalline copolymer and the diisocyanate groups of the cross-linker. The wires showed light-responsive bending towards the direction of the incident UV light at room temperature. Uncross-linked wires, drawn from the pure azobenzene copolymer, presented the same UV light-induced bending properties.

Blue phases and twist grain boundary phases (TGBA and TGBC) in a series of fluoro-substituted chiral tolane derivatives

A series of fluoro-substituted tolane derivatives: (R)-1-methylheptyl 3-fluoro-4-(3-fluoro-4- n alkoxybenzoyloxy)tolane-4-carboxylates is reported. Some members of this series exhibit the phase sequence: Cr-SmC*-TGBC-TGBA-BPI-BPII-BPIII-I. The blue phases, the TGBA and TGBC phases and the SmC* phase were characterized in detail by microscopic observation, differential scanning calorimetry, helical pitch measurements, X-ray structural analysis and electro-optical study. The blue phases directly next to the TGBA phase were shown to be a new type of blue phase exhibiting smectic ordering. A commensurate TGBC phase with constant number of slabs per pitch was observed.

Smectic polymer vesicles

Polymer vesicles are stable robust vesicles made from block copolymer amphiphiles. Recent progress in the chemical design of block copolymers opens up the exciting possibility of creating a wide variety of polymer vesicles with varying fine structure, functionality and geometry. Polymer vesicles not only constitute useful systems for drug delivery and micro/nano-reactors but also provide an invaluable arena for exploring the ordering of matter on curved surfaces embedded in three dimensions. By choosing suitable liquid-crystalline polymers for one of the copolymer components, one can create vesicles with smectic stripes. Smectic order on shapes of spherical topology inevitably possesses topological defects (disclinations) that are themselves distinguished regions for potential chemical functionalization and nucleators of vesicle budding. Here we report on glassy striped polymer vesicles formed from amphiphilic block copolymers in which the hydrophobic block is a smectic liquid crystal polymer containing cholesteryl-based mesogens. The vesicles exhibit two-dimensional smectic order and are ellipsoidal in shape with defects, or possible additional budding into isotropic vesicles, at the poles.