Block Copolymer Vesicles Research Articles

Morphology of nematic and smectic vesicles

Recent experiments on vesicles formed from block copolymers with liquid-crystalline side chains reveal a rich variety of vesicle morphologies. The additional internal order ("structure") developed by these self-assembled block copolymer vesicles can lead to significantly deformed vesicles as a result of the delicate interplay between two-dimensional ordering and vesicle shape. The inevitable topological defects in structured vesicles of spherical topology also play an essential role in controlling the final vesicle morphology. Here we develop a minimal theoretical model for the morphology of the membrane structure with internal nematic/smectic order. Using both analytic and numerical approaches, we show that the possible low free energy morphologies include nano-size cylindrical micelles (nano-fibers), faceted tetrahedral vesicles, and ellipsoidal vesicles, as well as cylindrical vesicles. The tetrahedral vesicle is a particularly fascinating example of a faceted liquid-crystalline membrane. Faceted liquid vesicles may lead to the design of supramolecular structures with tetrahedral symmetry and new classes of nano-carriers.

Self-assembly of block copolymers

Block copolymer (BCP) self-assembly has attracted considerable attention for many decades because it can yield ordered structures in a wide range of morphologies, including spheres, cylinders, bicontinuous structures, lamellae, vesicles, and many other complex or hierarchical assemblies. These aggregates provide potential or practical applications in many fields. The present tutorial review introduces the primary principles of BCP self-assembly in bulk and in solution, by describing experiments, theories, accessible morphologies and morphological transitions, factors affecting the morphology, thermodynamics and kinetics, among others. As one specific example at a more advanced level, BCP vesicles (polymersomes) and their potential applications are discussed in some detail.

How Does Cross-Linking Affect the Stability of Block Copolymer Vesicles in the Presence of Surfactant?

Block copolymer vesicles are conveniently prepared directly in water at relatively high solids by polymerization-induced self-assembly using an aqueous dispersion polymerization formulation based on 2-hydroxypropyl methacrylate. However, dynamic light scattering studies clearly demonstrate that addition of small molecule surfactants to such linear copolymer vesicles disrupts the vesicular membrane. This causes rapid vesicle dissolution in the case of ionic surfactants, with nonionic surfactants proving somewhat less destructive. To address this problem, glycidyl methacrylate can be copolymerized with 2-hydroxypropyl methacrylate and the resulting epoxy-functional block copolymer vesicles are readily cross-linked in aqueous solution using cheap commercially available polymeric diamines. Such epoxy-amine chemistry confers exceptional surfactant tolerance on the cross-linked vesicles and also leads to a distinctive change in their morphology, as judged by transmission electron microscopy. Moreover, pendent unreacted amine groups confer cationic character on these cross-linked vesicles and offer further opportunities for functionalization.

PH-sensitive biocompatible block copolymer vesicles for drug delivery

Abstract summaryHighly biocompatible pH-sensitive block copolymer vesicles can be prepared by the self-assembly of biocompatible block copolymers. Vesicle formation occurred spontaneously on adjusting the solution pH, with the hydrophobic chains forming the vesicle membrane and hydrophilic chains fo

Aqueous Dispersion Polymerization: A New Paradigm for in Situ Block Copolymer Self-Assembly in Concentrated Solution

Reversible addition-fragmentation chain transfer polymerization has been utilized to polymerize 2-hydroxypropyl methacrylate (HPMA) using a water-soluble macromolecular chain transfer agent based on poly(2-(methacryloyloxy)ethylphosphorylcholine) (PMPC). A detailed phase diagram has been elucidated for this aqueous dispersion polymerization formulation that reliably predicts the precise block compositions associated with well-defined particle morphologies (i.e., pure phases). Unlike the ad hoc approaches described in the literature, this strategy enables the facile, efficient, and reproducible preparation of diblock copolymer spheres, worms, or vesicles directly in concentrated aqueous solution. Chain extension of the highly hydrated zwitterionic PMPC block with HPMA in water at 70 °C produces a hydrophobic poly(2-hydroxypropyl methacrylate) (PHPMA) block, which drives in situ self-assembly to form well-defined diblock copolymer spheres, worms, or vesicles. The final particle morphology obtained at full monomer conversion is dictated by (i) the target degree of polymerization of the PHPMA block and (ii) the total solids concentration at which the HPMA polymerization is conducted. Moreover, if the targeted diblock copolymer composition corresponds to vesicle phase space at full monomer conversion, the in situ particle morphology evolves from spheres to worms to vesicles during the in situ polymerization of HPMA. In the case of PMPC(25)-PHPMA(400) particles, this systematic approach allows the direct, reproducible, and highly efficient preparation of either block copolymer vesicles at up to 25% solids or well-defined worms at 16-25% solids in aqueous solution.

Optically Triggered Dissociation of Kinetically Stabilized Block Copolymer Vesicles in Aqueous Solution

We demonstrate a strategy for using an optical stimulus to trigger the dissociation of block copolymer (BCP) vesicles in aqueous solution. The BCP, comprising hydrophilic poly(ethylene oxide) (PEO) and a block of poly(methacrylic acid) bearing a number of spiropyran methacrylate comonomer units (P(MAA-co-SPMA)), was allowed to firstly self-assemble into large vesicles in aqueous solution at pH=3 with protonated carboxylic acid groups, and then become kinetically stable at pH=8 due to the glassy vesicle membrane of P(MAA-co-SPMA). Fast dissociation of the vesicles was achieved through a cascade of events triggered by UV-induced isomerization from neutral spiropyran to charged merocyanine in the membrane.

Metallic Nanoparticle Block Copoloymer Vesicles with Enhanced Optical Properties.

The fabrication and characterization of template silver nanoshell structures and the encapsulation of gold nanoparticles using biocompatible poly(oxyethylene)-poly(butylene) diblock co-polymer vesicles is described in this work. These vesicles have a narrow diameter size distribution around 200 nm. Silver nanoparticles (ϕ = 1–10 nm) functionalized with decanethiol were successfully entrapped in the hydrophobic membrane and non-functionalized gold nanoparticles (ϕ = 3.0–5.5 nm) were encapsulated in the vesicle core. Transmission Electron Microscopy confirms the localisation of the particles; silver functionalized nanoparticles appear to thicken the vesicle membrane as shown with TEM image analysis. The enhancement of the optical properties is confirmed using transmission spectrophotometry; the 430 nm plasmon resonance peak of the silver nanoparticles was replaced by a broader extinction spectrum to beyond 700 nm (O.D. = 0.8). For a number density of 4.8 × 1012 mL−1 the scattering cross section was calculated to be 0.92 × 10−4 μm2 with a scattering coefficient of 0.44 mm−1. The measurements indicate scattering cross section of 3.8 × 10−5 μm2, attenuation coefficient of 0.18 mm−1 and extinction efficiency equal to 1.2 × 10−3. Stable and biocompatible block co-polymer vesicles can potentially be used as plasmon-resonant optical contrast agents for biomedical applications.

Block Copolymer Vesicle Permeability Measured by Osmotic Swelling and Shrinking

Vesicle response to osmotic shock provides insight into membrane permeability, a highly relevant value for applications ranging from nanoreactor experimentation to drug delivery. The osmotic shock approach has been employed extensively to elucidate the properties of phospholipid vesicles (liposomes) and of varieties of polymer vesicles (polymersomes). This study seeks to compare the membrane response for two varieties of polymersomes, a comb-type siloxane surfactant, poly(dimethylsiloxane)-g-poly(ethylene oxide) (PDMS-g-PEO), and a diblock copolymer, polybutadiene-b-poly(ethylene oxide) (PBut-b-PEO). Despite similar molecular weights and the same hydrophilic block (PEO), the two copolymers possess different hydrophobic blocks (PBut and PDMS) and corresponding glass transition temperatures (-31 and -123 °C, respectively). Dramatic variations in membrane response are observed during exposure to osmotic pressure differences, and values for polymer membrane permeability to water are extracted. We propose an explanation for the observed phenomena based on the respective properties of the PBut-b-PEO and PDMS-g-PEO membranes in terms of cohesion, thickness, and fluidity.

Imaging of block copolymer vesicles in solvated state by wet scanning transmission electron microscopy

Morphology of polystyrene-block-poly(acrylic acid) vesicles was imaged by various modes of scanning electron microscopy (SEM), including recently developed wet scanning transmission electron microscopy (wet-STEM) by means of which we were able to follow the decrease in the thickness of a liquid solvent layer around the vesicles during controlled evaporation of water from the sample. Results show that wet-STEM allows for imaging of nanosized polymeric particles in the presence of the solvent.

Functionalization of Block Copolymer Vesicle Surfaces

In dilute aqueous solutions certain amphiphilic block copolymers self-assemble into vesicles that enclose a small pool of water with a membrane. Such polymersomes have promising applications ranging from targeted drug-delivery devices, to biosensors, and nanoreactors. Interactions between block copolymer membranes and their surroundings are important factors that determine their potential biomedical applications. Such interactions are influenced predominantly by the membrane surface. We review methods to functionalize block copolymer vesicle surfaces by chemical means with ligands such as antibodies, adhesion moieties, enzymes, carbohydrates and fluorophores. Furthermore, surface-functionalization can be achieved by self-assembly of polymers that carry ligands at their chain ends or in their hydrophilic blocks. While this review focuses on the strategies to functionalize vesicle surfaces, the applications realized by, and envisioned for, such functional polymersomes are also highlighted.

Doxorubicin Loaded Magnetic Polymersomes: Theranostic Nanocarriers for MR Imaging and Magneto-Chemotherapy

Hydrophobically modified maghemite (γ-Fe(2)O(3)) nanoparticles were encapsulated within the membrane of poly(trimethylene carbonate)-b-poly(l-glutamic acid) (PTMC-b-PGA) block copolymer vesicles using a nanoprecipitation process. This formation method gives simple access to highly magnetic nanoparticles (MNPs) (loaded up to 70 wt %) together with good control over the vesicles size (100-400 nm). The simultaneous loading of maghemite nanoparticles and doxorubicin was also achieved by nanoprecipitation. The deformation of the vesicle membrane under an applied magnetic field has been evidenced by small angle neutron scattering. These superparamagnetic hybrid self-assemblies display enhanced contrast properties that open potential applications for magnetic resonance imaging. They can also be guided in a magnetic field gradient. The feasibility of controlled drug release by radio frequency magnetic hyperthermia was demonstrated in the case of encapsulated doxorubicin molecules, showing the viability of the concept of magneto-chemotherapy. These magnetic polymersomes can be used as efficient multifunctional nanocarriers for combined therapy and imaging.

Construction of a smart glutathione peroxidase mimic with temperature responsive activity based on block copolymer

To construct a smart artificial antioxidative enzyme on a nano-scaffold, a novel method for designing glutathione peroxidase (GPx) active sites on block copolymer vesicles was developed by simple blending predesigned temperature-sensitive block copolymers with the main catalytic units of GPx. A series of functional block copolymers, poly(N-isopropylacrylamide)-b-polyacrylamides loaded with recognition and catalytic sites, were synthesized viaATRP and click chemistry. Through altering the molar ratio of the functional copolymers, the optimum GPx mimic based on copolymer vesicles was obtained by self-assembly of temperature-sensitive block copolymers through a blending process. Significantly, the catalytic activity of the optimum GPx mimic can be well modulated by changing the temperature. It was proved that the change in self-assembly structure of the block copolymer played an important role in the modulation of the catalytic activity. This method not only bodes well for designing smart antioxidative enzyme mimics that could be used in cosmetics as antioxidative additives but also highlights the construction of other regulatory biologically related functional biomaterials.

Light-responsive block copolymer vesicles based on a photo-softening effect

We report the synthesis and study of two series of amphiphilic block copolymers (BCPs) of which the hydrophilic block is either poly(acrylic acid) (PAA) or poly(N,N-dimethylacrylamide) (PDMA) and the hydrophobic block is a side-chain liquid crystalline polymer (SCLCP) bearing biphenyl mesogens in majority and azobenzene mesogens in minority, namely, a random copolymer of 6-[4-(4-cyanophenyl)phenoxyl]hexyl acrylate with 6-[4-(4-methoxyphenylazo)phenoxyl]hexyl acrylate (P(BiPA-co-Azo)). Samples of both BCPs, PDMA-b-P(BiPA-co-Azo) and PAA-b-P(BiPA-co-Azo), could form large vesicles in aqueous solution with a SCLCP membrane. The BCPs were designed for investigating photoinduced order-disorder transition of the mesogens confined inside the vesicle membrane as a result of the trans–cisphotoisomerization of azobenzene and the LC cooperative effect. From photo-optical measurements on a BCP vesicle solution, we found evidence that a photoinduced LC order–disorder transition could occur inside the vesicle membrane in aqueous solution. Moreover, using a pH-sensitive fluorescent probe, we studied the photo-softening effect on the proton transfer across the vesicle membrane. Similar to plasticization of the vesicle membrane upon addition of a good solvent in aqueous solution, photo-induced softening could increase the rate of proton diffusion from inside to outside of the vesicle through the SCLCP membrane.

Patterns of surface immobilized block copolymer vesicle nanoreactors

The immobilization and positioning of ultra small reaction vessels on solid supports open new pathways in applications such as lab-on-a-chip, sensors, microanalyses and microreactors. In our work block copolymer vesicles made from polystyrene- block-polyacrylic acid (PS- b-PAA) were immobilized from aqueous medium onto 3-amino propyl trimethoxysilane functionalized silicon surfaces exploiting electrostatic interactions. The immobilization of the vesicles was investigated by Fourier transform infrared (FTIR) spectroscopy, as well as fluorescence optical and atomic force microscopy (AFM). In addition, the influence of pH and ionic strength on the surface coverage of vesicles bound to the surface was elucidated. Finally micro-molding in capillaries (MIMIC) was utilized to create line patterns of the vesicles containing the enzyme trypsin and the fluorogenic substrate rhodamine 110 bisamide. The selective positioning of vesicle nanoreactors in conjunction with electrostatic immobilization serves as a proof of principle for potential applications in real-time observation of confined chemical reaction inside vesicles as nanocontainers and for the fabrication of integrated microarray systems.

Polymersomes with Ionic Liquid Interiors Dispersed in Water

We describe polymersomes with ionic liquid interiors dispersed in water. The vesicles are prepared via a simple and spontaneous migration of poly(butadiene-b-ethylene oxide) (PB-PEO) block copolymer vesicles from a hydrophobic ionic liquid, 1-ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide ([EMIM][TFSI]), to water at room temperature. As PB is insoluble in both water and [EMIM][TFSI] and PEO is well solvated in both media, the vesicles feature a PB membrane with PEO brushes forming both interior and exterior coronas. The robust and stable PB-PEO vesicles migrate across the liquid-liquid interface with their ionic liquid interiors intact and form a stabilized aqueous dispersion of vesicles enclosing microscopic ionic liquid pools. The nanostructure of the vesicles with ionic liquid interiors dispersed in water is characterized by direct visualization using cryogenic transmission electron microscopy. Upon heating, the vesicles can be quantitatively transferred back to [EMIM][TFSI], thus enabling facile recovery. The reversible transport capability of the shuttle system is demonstrated by the use of distinct hydrophobic dyes, which are selectively and simultaneously loaded in the vesicle membrane and interior. Furthermore, the fluorescence of the loaded dyes in the vesicles enables probing of the microenvironment of the vesicular ionic liquid interior through solvatochromism and direct imaging of the vesicles using laser scanning confocal microscopy. This vesicle system is of particular interest as a nanocarrier or nanoreactor for reactions, catalysis, and separations using ionic liquids.

Characterization of Polymer Nanoparticles by Asymmetrical Flow Field Flow Fractionation (AF-FFF)

We present the characterization of different polymeric nanoparticles with asymmetrical flow field-flow fractionation (AF-FFF) in different solvents and additional, independent methods such as static and dynamic light scattering (SLS, DLS) in solution and transmission electron microscopy (TEM) and atomic force microscopy (AFM) for the visualization of the nanoparticles on solid substrates. AF-FFF proves to be a powerful technique to determine average sizes of nanoparticles such as multifunctional polyorganosiloxane nanospheres both, in aqueous dispersion and in organic solvents such as toluene. In addition, dye loaded block copolymer vesicles and cylindrical polyelectrolyte type polymacromonomers are successfully analyzed by AF-FFF and the obtained results are compared to the other techniques used.

A simple method to achieve high doxorubicin loading in biodegradable polymersomes

Doxorubicin (Dox), an anthracycline anticancer drug, was successfully incorporated into block copolymer vesicles of poly(trimethylene carbonate)- b-poly( l-glutamic acid) (PTMC- b-PGA) by a solvent-displacement (nanoprecipitation) method. pH conditions were shown to have a strong influence on loading capacity and release profiles. Substantial drug loading (47% w/w) was achieved at pH 10.5. After pH neutralization, aqueous dispersions of drug-loaded vesicles were found stable for a prolonged period of time (at least 6 months) without vesicle disruption or drug precipitation. Dox-loaded vesicles exhibited in vitro pH and temperature-dependent drug release profiles: release kinetics fastened in acid conditions or by increasing temperature. These features strongly support the interest of developing PTMC- b-PGA polymersomes as carriers for the controlled delivery of Dox.

PH‐Responsive Vesicles from a Schizophrenic Diblock Copolymer

AbstractA novel tertiary amine and amino acid‐based “schizophrenic” pH‐responsive block copolymer, PDEA‐b‐PAP, has been synthesized by RAFT polymerization. By directly dissolving this copolymer in acid or basic aqueous solution block copolymer vesicles with switchable coronas and membranes were prepared. These novel assemblies were characterized using TEM, DLS, zeta potential, and SLS analysis.magnified image

Vesicle formation of polystyrene-block-poly (ethylene oxide) block copolymers induced by supercritical CO2 treatment

A novel route for a preparation of polystyrene-block-poly(ethylene oxide) (PS-b-PEO) block copolymer vesicles induced by supercritical carbon dioxide (scCO2) is demonstrated. When PS-b-PEO block copolymer solutions in tetrahydrofuran (THF) are treated with scCO2 at 70 °C for different times, PS-b-PEO copolymers first assemble into aggregated spheres; then aggregated spheres change into large compound micelles and finally evolve into vesicles. The possible formation mechanism of the vesicles is discussed.

Covalent Attachment of Polymersomes to Surfaces

We show that vesicles made of block copolymers with aldehyde end groups can be covalently attached to aminated and non-aminated, untreated glass surfaces. The attached vesicles were sufficiently stable to allow a detailed investigation of vesicle shapes by confocal laser scanning microscopy (CLSM) and AFM in aqueous solutions allowing reconstruction of 3D images of the vesicle structure. Covalently attached PCL-PEO, PLA-PEO, and PI-PEO block copolymer vesicles have different footprint areas and different shapes due to their differences in bilayer stiffness.