Self-assembly Of Diblock Copolymers Research Articles

Inhaled siRNA nanoparticles targeting IL11 inhibit lung fibrosis and improve pulmonary function post-bleomycin challenge.

Interleukin-11 (IL-11) is a profibrotic cytokine essential for the differentiation of fibroblasts into collagen-secreting, actin alpha 2, smooth muscle–positive (ACTA2+) myofibroblasts, driving processes underlying the pathogenesis of idiopathic pulmonary fibrosis (IPF). Here, we developed an inhalable and mucus-penetrative nanoparticle (NP) system incorporating siRNA against IL11 (siIL11@PPGC NPs) and investigated therapeutic potential for the treatment of IPF. NPs are formulated through self-assembly of a biodegradable PLGA-PEG diblock copolymer and a self-created cationic lipid-like molecule G0-C14 to enable efficient transmucosal delivery of siIL11. Noninvasive aerosol inhalation hindered fibroblast differentiation and reduced ECM deposition via inhibition of ERK and SMAD2. Furthermore, siIL11@PPGC NPs significantly diminished fibrosis development and improved pulmonary function in a mouse model of bleomycin-induced pulmonary fibrosis without inducing systemic toxicity. This work presents a versatile NP platform for the locally inhaled delivery of siRNA therapeutics and exhibits promising clinical potential in the treatment of numerous respiratory diseases, including IPF.

Impact of Side-Chain Length on the Self-Assembly of Linear-Bottlebrush Diblock Copolymers

Impact of Side-Chain Length on the Self-Assembly of Linear-Bottlebrush Diblock Copolymers

Block Copolymer Modified Nanonetwork Epoxy Resin for Superior Energy Dissipation.

Herein, this work aims to fabricate well-ordered nanonetwork epoxy resin modified with poly(butyl acrylate)-b-poly(methyl methacrylate) (PBA-b-PMMA) block copolymer (BCP) for enhanced energy dissipation using a self-assembled diblock copolymer of polystyrene-b-poly(dimethylsiloxane) (PS-b-PDMS) with gyroid and diamond structures as templates. A systematic study of mechanical properties using nanoindentation of epoxy resin with gyroid- and diamond-structures after modification revealed significant enhancement in energy dissipation, with the values of 0.36 ± 0.02 nJ (gyroid) and 0.43 ± 0.03 nJ (diamond), respectively, when compared to intrinsic epoxy resin (approximately 0.02 ± 0.002 nJ) with brittle characteristics. This enhanced property is attributed to the synergic effect of the deliberate structure with well-ordered nanonetwork texture and the toughening of BCP-based modifiers at the molecular level. In addition to the deliberate structural effect from the nanonetwork texture, the BCP modifier composed of epoxy-philic hard segment and epoxy-phobic soft segment led to dispersed soft-segment domains in the nanonetwork-structured epoxy matrix with superior interfacial strength for the enhancement of applied energy dissipation.

Side-Chain Density Driven Morphology Transition in Brush–Linear Diblock Copolymers

We report the synthesis and self-assembly of brush-linear diblock copolymers with variable side-chain length and density. Poly(pentafluorophenyl acrylate-g-ethylene glycol)-b-polystyrene ((PPFPA-g-PEG)-b-PS) brush-linear diblock copolymers are prepared by sequential reversible addition-fragmentation chain transfer (RAFT) polymerization of PPFPA and PS, followed by postpolymerization reaction between the precursor PPFPA-b-PS diblock copolymer and amine-functionalized PEG. By controlling the PEG chain length and the degree of substitution, we obtained brush-linear diblock copolymers with different side-chain lengths and densities. The solid-state morphologies of the diblocks are then examined by small-angle X-ray scattering (SAXS). At low PEG side-chain density, the segregation of PEG and PS away from PPFPA leads to the formation of PEG and PS lamellar domains with PPFPA in the interface. At high PEG side-chain density, the segregation is between the PPFPA-g-PEG brush block and the PS linear block, and the domain morphology is determined by the composition of the brush block. A partial experimental phase diagram is presented, and it illustrates the importance of both side-chain length and density on the microdomain morphology of brush-linear diblock copolymers.

A Globally Convergent Modified Newton Method for the Direct Minimization of the Ohta--Kawasaki Energy with Application to the Directed Self-Assembly of Diblock Copolymers

We propose a fast and robust scheme for the direct minimization of the Ohta-Kawasaki energy that characterizes the microphase separation of diblock copolymer melts. The scheme employs a globally convergent modified Newton method with line search which is shown to be mass-conservative, energy-descending, asymptotically quadratically convergent, and three orders of magnitude more efficient than the commonly-used gradient flow approach. The regularity and the first-order condition of minimizers are analyzed. A numerical study of the chemical substrate guided directed self-assembly of diblock copolymer melts, based on a novel polymer-substrate interaction model and the proposed scheme, is provided.

Formation of hierarchical platelets with morphological control by self-assembly of an azobenzene-containing liquid crystalline diblock copolymer

The diblock copolymer PEG-b-PAzoMA self-assembled into abundant assemblies through a heating-annealing approach, including leaf-type, macro-flower-type, and rectangular platelets by manipulating the concentration and the cooling rate of the solution.

Polymerization-induced self-assembly and disassembly during the synthesis of thermoresponsive ABC triblock copolymer nano-objects in aqueous solution.

Polymerization-induced self-assembly (PISA) has been widely utilized as a powerful methodology for the preparation of various self-assembled AB diblock copolymer nano-objects in aqueous media. Moreover, it is well-documented that chain extension of AB diblock copolymer vesicles using a range of hydrophobic monomers via seeded RAFT aqueous emulsion polymerization produces framboidal ABC triblock copolymer vesicles with adjustable surface roughness owing to microphase separation between the two enthalpically incompatible hydrophobic blocks located within their membranes. However, the utilization of hydrophilic monomers for the chain extension of linear diblock copolymer vesicles has yet to be thoroughly explored; this omission is addressed for aqueous PISA formulations in the present study. Herein poly(glycerol monomethacrylate)-poly(2-hydroxypropyl methacrylate) (G-H) vesicles were used as seeds for the RAFT aqueous dispersion polymerization of oligo(ethylene glycol) methyl ether methacrylate (OEGMA). Interestingly, this led to polymerization-induced disassembly (PIDA), with the initial precursor vesicles being converted into lower-order worms or spheres depending on the target mean degree of polymerization (DP) for the corona-forming POEGMA block. Moreover, construction of a pseudo-phase diagram revealed an unexpected copolymer concentration dependence for this PIDA formulation. Previously, we reported that PHPMA-based diblock copolymer nano-objects only exhibit thermoresponsive behavior over a relatively narrow range of compositions and DPs (see Warren et al., Macromolecules, 2018, 51, 8357–8371). However, introduction of the POEGMA coronal block produced thermoresponsive ABC triblock nano-objects even when the precursor G-H diblock copolymer vesicles proved to be thermally unresponsive. Thus, this new approach is expected to enable the rational design of new nano-objects with tunable composition, copolymer architectures and stimulus-responsive behavior.

Para Fluoro-Thiol Clicked Diblock-Copolymer Self-Assembly: Towards a New Paradigm for Highly Proton-Conductive Membranes

Para Fluoro-Thiol Clicked Diblock-Copolymer Self-Assembly: Towards a New Paradigm for Highly Proton-Conductive Membranes

Self-Assembly of Asymmetric Diblock Copolymers under the Spherical Confinement

The self-assembly of asymmetric AB diblock copolymer melts under the spherical confinement with surface preference to the minority A-block has been investigated using the pseudospectral method of self-consistent field theory coupled with the masking technique. A phase diagram with respect to the volume fraction and the radius of the spherical cavity is constructed, mainly consisting of different spherical and cylindrical structures. In contrast to the bulk disorder/sphere/cylinder/gyroid transitions, the spherical confinement shifts the corresponding transitions toward small volume fraction. For the spherical structures, the number of spherical domains increases with the radius of the cavity, but it changes discontinuously. In general, the higher the symmetry of the sphere arrangement, the larger the stability region of the spherical structure. In addition, a number of interesting cylindrical structures are predicted, such as truncated single-helix, double-toroid, and three-/four-/six-hole cages. Compared with the spherical structures, the transitions between the different cylindrical structures are more difficult to understand because the spherical confinement impacts not only the length of the cylindrical domain but also its orientation. Our work provides an insight into the influence of the spherical confinement on the self-assembly of block copolymers, especially on the arrangement of soft spherical domains.

Dynamics of pearling instability in polymersomes: The role of shear membrane viscosity and spontaneous curvature

The stability of copolymer tethers is investigated theoretically. Self-assembly of diblock or triblock copolymers can lead to tubular polymersomes, which are known experimentally to undergo shape instability under thermal, chemical, and tension stresses. It leads to a periodic modulation of the radius, which evolves to assembly line pearls connected by tiny tethers. We study the contributions of shear surface viscosity and spontaneous curvature and their interplay to understand the pearling instability. The performed linear analysis of stability of this cylinder-to-pearls transition shows that such systems are unstable if the membrane tension is larger than a finite critical value contrary to the Rayleigh–Plateau instability, an already known result, or if the spontaneous curvature is in a specific range, which depends on membrane tension. For the case of spontaneous curvature-induced shape instability, two dynamical modes are identified. The first one is analog to the tension-induced instability with a marginal mode. Its wavenumber associated with the most unstable mode decreases continuously to zero as membrane viscosity increases. The second one has a finite range of unstable wavenumbers. The wavenumber of the most unstable mode tends to be constant as membrane viscosity increases. In this mode, its growth rate becomes independent of the bulk viscosity in the limit of high membrane viscosity and behaves as a pure viscous surface.

Self-assembly of gradient copolymers in a selective solvent. New structures and comparison with diblock and statistical copolymers

We perform comparative studies of self-assembly of equivalent statistical, diblock and gradient AB copolymers in a selective solvent using dissipative particle dynamics simulations. Both effects of the fraction of soluble and insoluble groups, selectivity of the solvent and degree of immiscibility of A and B groups on self-assembled structures are studied. With a simplified model of the statistical copolymer we predict macroscopic phase segregation, when non-aggregated chains coexist with precipitate. The later can be dense or swollen (physical gel) depending on degree of immiscibility of the A and B groups. For the case of diblock copolymer solutions, we predict thermodynamic stability of few structures: spherical and worm-like micelles, rings, vesicles and precipitate. We develop a simple theory, which allows calculating free energies of worms and rings (closed worms) and explaining transition between the structures. A number of diagrams of states is constructed. In case of gradient copolymers, two scenarios of self-assembly are predicted. The spherical micelles of gradient copolymer can aggregate with each other forming worms, rings and vesicles through aggregation of coronae (so-called sticky corona), which contain insoluble groups, if the fraction of insoluble groups per chain is not high. Herewith, the core of the assembled structures remains multidomain despite a high interfacial tension. The second (“diblock-like”) scenario is realized when the fraction of insoluble groups is high enough. In this case the core of worms, rings and vesicles is practically a monodomain, however, solvophilic groups can be intercalated into the core due to the primary structure of the copolymer. A new structure of a multi-compartment vesicle on the basis of gradient copolymers is predicted.

Recent Advances in Polyallenes: Preparation, Self-Assembly, and Stimuli-Responsiveness.

Polyallenes, as a typical type of reactive polymers, are of great significance and have aroused widespread interest because they contain double bonds that can be post-modified into other functionalities to afford varieties of functional materials. This Minireview firstly highlights the recent advances in the preparation of polyallenes, including preparation of helical polyallenes through directly polymerization of chiral allene monomers or helix-sense-selective polymerization (HSSP) of achiral allene monomers, synthesis of 1,2-regulated polyallenes and 2,3-regulated polyallenes via selective polymerization of allene monomers, polymerization of allene monomers catalyzed by Ni(II)-terminated poly(3-hexylthiophene) (P3HT), and so on. Then, latest progress on the self-assembly and stimuli-responses of polyallene-based diblock, ABA and ABC triblock copolymers is summarized. We hope this Minireview will inspire more interest in developing polyallenes and encourage further advances in functional materials.

Synthesis of Multicompositional Onion-like Nanoparticles via RAFT Emulsion Polymerization.

Synthesis of multicompositional polymeric nanoparticles of diameters 100-150 nm comprising well-defined multiblock copolymers reaching from the particle surface to the particle core was conducted using surfactant-free aqueous macroRAFT emulsion polymerization. The imposed constraints on chain mobility as well as chemical incompatibility between the blocks result in microphase separation, leading to formation of an onion-like multilayered particle morphology with individual layer thicknesses of approximately 20 nm. The approach provides considerable versatility in particle morphology design as the composition of individual layers as well as the number of layers can be tailored as desired, offering more complex particle design compared to approaches relying on self-assembly of preformed diblock copolymers within particles. Microphase separation can occur in these systems under conditions where the corresponding bulk system would not theoretically result in microphase separation.

Self-Patterning Polyelectrolyte Multilayer Films: Influence of Deposition Steps and Drying in a Vacuum.

Typically, laterally patterned films are fabricated by lithographic techniques, external fields, or di-block copolymer self-assembly. We investigate the self-patterning of polyelectrolyte multilayers, poly(diallyldimethylammonium) (PDADMA)/poly(styrenesulfonate) (PSS)short. The low PSS molecular weight (Mw(PSSshort) = 10.7 kDa) is necessary because PSSshort is somewhat mobile within a PDADMA/PSSshort film, as demonstrated by the exponential growth regime at the beginning of the PDADMA/PSSshort multilayer build-up. No self-patterning was observed when the PDADMA/PSS film consisted of only immobile polyelectrolytes. Atomic force microscopy images show that self-patterning begins when the film consists of seven deposited PDADMA/PSSshort bilayers. When more bilayers are added, the surface ribbing evolved into bands, and circular domains were finally observed. The mean distance between the surface structures increased monotonously with the film thickness, from 70 to 250 nm. Scanning electron microscopy images showed that exposure to vacuum resulted in thinning of the film and an increase in the mean distance between domains. The effect is weaker for PSSshort-terminated films than for PDADMA-terminated films. The mechanism leading to domain formation during film build-up and the effect of post-preparation treatment are discussed.

Exploiting Self-assembly of Block Copolymers to Fabricate Nanocomposite Thin Films with Controlled Morphology at Nanoscale

As the advantageous properties of nanoparticles (NPs) often emerge only when appropriate coupling and exchange phenomena between the NPs can take place, the control of the inter-particle distance, regular ordering, and location of the nanoparticles onto solid supports is a critical issue. A robust method to control the spatial organization of NPs onto solid supports, based on the use of self-assembling di-block copolymers (BCPs) as structure-guiding material, is reported. Two different polystyrene-b-poly(methyl methacrylate) (PS-b-PMMA) BCPs, characterized by a different PS volume fraction, were used as matrices for the fabrication of nanocomposite thin films with cylindrical and lamellar morphologies controlled at the nanoscale. Selective inclusion of surface functionalized gold (Au) and zinc oxide (ZnO) NPs of appropriate size in the PS nanodomains was achieved from dispersions of the BCPs and NPs in a common solvent. The orientation of the BCPs cylinder and lamellar nanodomains in spin-coated thin films was controlled by solvent and thermal annealing protocols, coupled with techniques of surface neutralization.

Co-Nonsolvency Effect in Solutions of Poly(methyl methacrylate)-b-poly(N-isopropylacrylamide) Diblock Copolymers in Water/Methanol Mixtures

The self-assembly of the thermoresponsive amphiphilic diblock copolymer PMMA21-b-PNIPAM283 is studied in different water/methanol mixtures. It consists of a short hydrophobic poly(methyl methacrylate) block and a long thermoresponsive poly(N-isopropylacrylamide) block. Adding methanol as a cosolvent causes the PNIPAM block, which is soluble in both pure water and pure methanol, to collapse due to the so-called co-nonsolvency effect. Meanwhile, the addition of methanol reduces the incompatibility of the PMMA block with water. By means of turbidimetry and differential scanning calorimetry, the solvent-composition-dependent phase diagram is constructed. Dynamic light scattering and synchrotron radiation-based small-angle X-ray scattering provide structural information at 20 °C in dependence on the solvent composition. In water-rich solvent mixtures, self-assembled spherical core–shell micelles are formed. The internal structure of the micelles is adjusted by the solvent compositions in two ways: methanol softens the PMMA micellar core, while it causes the shrinkage of the PNIPAM micellar shell. In methanol-rich solvent mixtures beyond the miscibility gap, the copolymers are molecularly dissolved chains. They are collapsed near the coexistence line, while they become random coils as the methanol content increases. We propose that the internal morphology of the micelles and the conformation of the dissolved chains depend strongly on the solvent composition, as a consequence of the superposed co-nonsolvency effect of PNIPAM and the overall enhanced solvation of PMMA when adding methanol.

Self-assembly of Amphiphilic Diblock Copolymers Induced by Liquid-Liquid Phase Separation

Self-assembly of Amphiphilic Diblock Copolymers Induced by Liquid-Liquid Phase Separation

Light-Induced Reversible Hierarchical Self-Assembly of Amphiphilic Diblock Copolymers into Microscopic Vesicles with Tunable Optical and Nanocarrier Properties.

In contrast to the conventional hierarchical self-assembly process, effective methods to enable reversible hierarchical self-assembly of block copolymers are comparatively few and limited in scope. Herein, we report, for the first time, a simple yet robust strategy for light-induced reversible hierarchical self-assembly of an amphiphilic diblock copolymer, poly(4-vinylpyridine)-block-poly[6-[4-(4-butyloxyphenylazo)phenoxy]hexyl methacrylate] (denoted P4VP-b-PAzoMA). The hierarchical structures are constructed via a two-step self-assembly process (first-level reverse micelles, second-level compound micelles, and rearrangement into micrometer-sized vesicles) driven by use of solvent. Intriguingly, because of reversible photoinduced trans-to-cis isomerization of azobenzene moieties in PAzoMA, the vesicles could disassemble into subunits upon UV light and then recover the nearly identical vesicular morphology upon visible light. Such a reversible hierarchical self-assembly process is accompanied by reversible fluorescence, encapsulation, and controlled release of dyes and can be used as a template for the synthesis of nanoparticles. Clearly, the ability to render the light-enabled reversible hierarchical self-assembly provides a unique platform for smart delivery vehicles and templates for nanomaterials.

Near-Infrared Photo-controlled Permeability of a Biomimetic Polymersome with Sustained Drug Release and Efficient Tumor Therapy.

Synthetic polymersomes have structure similarity to bio-vesicles and could disassemble in response to stimuli for "on-demand" release of encapsulated cargos. Though widely applied as a drug delivery carrier, the burst release mode with structure complete destruction is usually taken for most responsive polymersomes, which would shorten the effective drug reaction time and impair the therapeutic effect. Inspired by the cell organelles' communication mode via regulating membrane permeability for transportation control, we highlight here a biomimetic polymersome with sustained drug release over a specific period of time via near-infrared (NIR) pre-activation. The polymersome is prepared by the self-assembling amphiphilic diblock copolymer P(OEGMA-co-EoS)-b-PNBOC and encapsulates the hypoxia-activated prodrug AQ4N and upconversion nanoparticle (PEG-UCNP) in its hydrophilic centric cavity. Thirty minutes of NIR pre-activation triggers cross-linking of NBOC and converts the permeability of the polymersome with sustained AQ4N release until 24 h after the NIR pre-activation. The photosensitizer EoS is activated and aggravates environmental hypoxic conditions during a sustained drug release period to boost the AQ4N therapeutic effect. The combination of sustained drug release with concurrent hypoxia intensification results in a highly efficient tumor therapeutic effect both intracellularly and in vivo. This biomimetic polymersome will provide an effective and universal tumor therapeutic approach.

The effect of topology of PEG chain on the stability of micelles in brine and serum

Polymeric micelles are promising vehicles for drug delivery these years. The stability of micelles in blood system is very important for the encapsulated therapeutic agents reaching the targeting area. However, generally, micelles are not stable in the presence of proteins and ions after being injected intravenously. The topology of polymer chain on the surface of micelles plays a key role on the stability of micelles. Here we have prepared flower micelles and the traditional micelles via self-assembly of triblock and diblock copolymer of polyethylene glycol (PEG) and poly(ε-caprolactone) (PCL) in water. The special PEG shell of flower micelles prevents micelles from ions and proteins, which endows the micelles with the ability to resist aggregation. The experiment results show that flower micelles are much more stable in the presence of serum and salt than traditional micelles, which indicates these micelles would be promising in drug delivery in the future.