Amphiphilic ABC Triblock Copolymers Research Articles

Amphiphilic pH-responsive ABC triblock copolymers via RAFT-mediated aqueous PISA and comparison with their A-b-(B-co-C) diblock copolymer counterparts

The influence of the macroRAFT agent architecture on the morphology of the self-assemblies obtained by aqueous RAFT dispersion polymerization in PISA is studied by comparing amphiphilic AC, A(B-co-C) diblocks and ABC triblock copolymers, constituted of N,N-dimethylacrylamide (DMAm = A), acrylic acid (AA = B) and N-cyanomethylacrylamide (CMAm = C) monomer units. The aim of this study is to better understand the impact of the presence of pH-sensitive acrylic acid units and their spatial distribution in block copolymers. Generally, the presence of a fully protonated intermediate block of PAA between the two blocks (based on PDMAm and PCMAm) favors the formation of higher-order morphologies. These ABC triblock copolymers assemblies are pH-responsive and can undergo morphological transitions through the controlled deprotonation or protonation of the PAA segment, but do not completely dissociate at high pH (i.e. when AA units are fully ionized) unlike their A(B-co-C) diblock counterparts, where the pH-responsive monomer unit is homogeneously distributed within the solvophobic block.

General Synthesis of Ultrafine Monodispersed Hybrid Nanoparticles from Highly Stable Monomicelles.

Ultrafine nanoparticles with organic-inorganic hybridization have essential roles in myriad applications. Over the past three decades, although various efforts on the formation of organic or inorganic ultrasmall nanoparticles have been made, ultrafine organic-inorganic hybrid nanoparticles have scarcely been achieved. Herein, a family of ultrasmall hybrid nanoparticles with a monodisperse, uniform size is synthesized by a facile thermo-kinetics-mediated copolymer monomicelle approach. These thermo-kinetics-mediated monomicelles with amphiphilic ABC triblock copolymers are structurally robust due to their solidified polystyrene core, endowing them with ultrahigh thermodynamic stability, which is difficult to achieve using Pluronic surfactant-based micelles (e.g., F127). This great stability combined with a core-shell-corona structure makes the monodispersed monomicelles a robust template for the precise synthesis of ultrasmall hybrid nanoparticles with a highly uniform size. As a demonstration, the obtained micelles/SiO2 hybrid nanoparticles display ultrafine sizes, excellent uniformity, monodispersity, and tunable structural parameters (diameters: 24-47 nm and thin shell thickness: 2.0-4.0 nm). Notably, this approach is universal for creating a variety of multifunctional ultrasmall hybrid nanostructures, involving organic/organic micelle/polymers (polydopamine) nanoparticles, organic/inorganic micelle/metal oxides (ZnO, TiO2 , Fe2 O3 ), micelle/hydroxides (Co(OH)2 ), micelle/noble metals (Ag), and micelle/TiO2 /SiO2 hybrid composites. As a proof of concept, the ultrasmall micelle/SiO2 hybrid nanoparticles demonstrate superior toughness as biomimetic materials.

One-Pot Synthesis of an Amphiphilic ABC Triblock Copolymer PEO-b-PEHOx-b-PEtOz and Its Self-Assembly into Nanoscopic Asymmetric Polymersomes

We report an efficient one-pot synthesis of a new biocompatible amphiphilic ABC triblock terpolymer: poly(ethylene oxide)-block-poly(2-(3-ethylheptyl)-2-oxazoline)-block-poly(2-ethyl-2-oxazoline) (...

A pH and UCST thermo-responsive tri-block copolymer (PAA-b-PDMA-b-P(AM-co-AN)) with micellization and gelatinization in aqueous media for drug release

A brand new pH and thermo-responsive amphiphilic ABC triblock copolymer of poly(acrylic acid)-block-poly(N,N-dimethyl acrylamide)-block-poly(acrylamide-co-acrylonitrile) (PAA-b-PDMA-b-P(AM-co-AN)) was applied as drug carrier systems.

Synthesis of Linear ABC Triblock Copolymers and Their Self‐Assembly in Solution

The self‐assembly of amphiphilic block copolymers has attracted the interest of a large number of research groups in the past two decades. Many examples have been reported using AB diblock copolymers, but the self‐assembly becomes more complex and shows a greater variety if ABC triblock copolymers are used. However, the synthesis of the polymer becomes more demanding since end‐group modifications or chain extensions become necessary. Using various kinds of polymerization techniques, pure triblock copolymers have been reported and their synthesis is covered in this review. Following the synthesis, a detailed and thorough analysis of the self‐assembly behaviour is the next step. We have selected promising and well characterized examples to show the range of self‐assembled structures possible, covering novel shapes of micelles but also polymersomes with an asymmetric membrane. Our selection of current examples in literature show the challenges and chances associated with amphiphilic ABC triblock copolymers.

Vesicles in Multiple Shapes: Fine-Tuning Polymersomes' Shape and Stability by Setting Membrane Hydrophobicity.

Amphiphilic block-copolymers are known to self-assemble into micelles and vesicles. In this paper, we discuss the multiple options between and beyond these boundaries using amphiphilic AB diblock and ABC triblock copolymers. We adjust the final structure reached by the composition of the mixture, by the preparation temperature, and by varying the time-scale of formation. This leads to the formation of vesicles and micelles, but also internal micelles in larger sheets, lamellar vesicles, and closed tubes, thus broadening the amount of self-assembly structures available and deepening our understanding of them.

PEO-b-PCL-b-PMOXA Triblock Copolymers: From Synthesis to Microscale Polymersomes with Asymmetric Membrane

We report a new family of amphiphilic ABC triblock copolymers: poly(ethylene oxide)-block-polycaprolactone-block-poly(2-methyl-2-oxazoline) (PEO-b-PCL-b-PMOXA). The synthesis is free of toxic reagents, well-controlled and results in polymers with ĐM < 1.25 and PMOXA length up to 25 units (2 kDa). We compare the self-assembly of PEO-b-PCL-b-PMOXA with PEO-b-PCL depending on PCL length and hydrophilic weight fraction (f) using the film rehydration method. Polymers self-assemble into different microscale structures, including polymersomes, which were studied by laser scanning microscopy. We proved the asymmetry of polymersome membrane by two independent methods, which confirmed the presence of a longer PEO block and the absence of a shorter PMOXA block on the outer surface of polymersomes.

Micellization and gelatinization in aqueous media of pH- and thermo-responsive amphiphilic ABC (PMMA82-b-PDMAEMA150-b-PNIPAM65) triblock copolymer synthesized by consecutive RAFT polymerization

The ABC triblock copolymer molecularly displays diverse properties in dilute solution and concentrated solution at different pH with elevated temperatures.

Perfluorocyclobutyl Aryl Ether-Based ABC Amphiphilic Triblock Copolymer.

A series of fluorine-containing amphiphilic ABC triblock copolymers comprising hydrophilic poly(ethylene glycol) (PEG) and poly(methacrylic acid) (PMAA), and hydrophobic poly(p-(2-(4-biphenyl)perfluorocyclobutoxy)phenyl methacrylate) (PBPFCBPMA) segments were synthesized by successive atom transfer radical polymerization (ATRP). First, PEG-Br macroinitiators bearing one terminal ATRP initiating group were prepared by chain-end modification of monohydroxy-terminated PEG via esterification reaction. PEG-b-PBPFCBPMA-Br diblock copolymers were then synthesized via ATRP of BPFCBPMA monomer initiated by PEG-Br macroinitiator. ATRP polymerization of tert-butyl methacrylate (tBMA) was directly initiated by PEG-b-PBPFCBPMA-Br to provide PEG-b-PBPFCBPMA-b-PtBMA triblock copolymers with relatively narrow molecular weight distributions (Mw/Mn ≤ 1.43). The pendant tert-butyoxycarbonyls were hydrolyzed to carboxyls in acidic environment without affecting other functional groups for affording PEG-b-PBPFCBPMA-b-PMAA amphiphilic triblock copolymers. The critical micelle concentrations (cmc) were determined by fluorescence spectroscopy using N-phenyl-1-naphthylamine as probe and the self-assembly behavior in aqueous media were investigated by transmission electron microscopy. Large compound micelles and bowl-shaped micelles were formed in neutral aqueous solution. Interestingly, large compound micelles formed by triblock copolymers can separately or simultaneously encapsulate hydrophilic Rhodamine 6G and hydrophobic pyrene agents.

Preparation of cylindrical multi-compartment micelles by the hierarchical self-assembly of ABC triblock polymer in solution

Amphiphilic linear ABC triblock copolymer PnBA28-b-PS37-b-P2VP73 was prepared by the RAFT method. Spherical patchy micelles and cylindrical MCMs were formed in different steps of its two-step hierarchical self-assembly in selected solvents.

Poly(methacrylic acid)-based AB and ABC block copolymer nano-objects prepared via RAFT alcoholic dispersion polymerization

A series of well-defined amphiphilic methacrylic AB diblock and ABC triblock copolymers are synthesized via polymerization-induced self-assembly using an alcoholic dispersion polymerization formulation.

Amphiphilic ABC Triblock Copolymers Tailored via RAFT Polymerization as Textile Surface Modifiers with Dual-Action Properties

We present the synthesis and characterization of two different kinds of triblock copolymers prepared via RAFT polymerization by only two synthetic steps applying a sequential monomer addition approach. Both triblock copolymers consist of a hydrophilic, a hydrophobic and an anchor block which is located in the middle or at the end of the polymer chains. In both triblock copolymer systems the hydrophobic blocks consist of randomly polymerized tert-butylstyrene (tBS) and n-hexyl acrylate (nHA) monomers in a ratio of approximately 2:1, respectively, whereas the hydrophilic blocks were accomplished by polymerization of N,N-dimethylacrylamide (DMA). As a result of the employed synthetic approach, every anchor block contains several N-acryloxysuccinimide (NAS) units besides tBS and nHA units in the case of the triblock copolymer with the central anchor block and DMA units in the case of the triblock copolymer with the terminal anchor block. The structures as well as the compositions of all synthesized polymers w...

Water-dispersible and biodegradable polymer micelles with good antibacterial efficacy

New amphiphilic ABC triblock copolymers have been designed and self-assembled into water-dispersible and biodegradable polymer micelles, which exhibit good antibacterial activities without quaternary ammonium moieties or the loading of any external antibiotics due to the increased local concentration of cationic charge in the polymer micelles compared to the un-self-assembled individual polymer chains.

Thermoresponsive triblock copolymers based on methacrylate monomers: effect of molecular weight and composition

A series of amphiphilic thermoresponsive ABC triblock copolymers was synthesised by Group Transfer Polymerisation (GTP). In total nine polymers were prepared based on the non-ionic hydrophobic n-butyl methacrylate (BuMA), the ionisable hydrophilic and thermoresponsive 2-(dimethylamino)ethyl methacrylate (DMAEMA) and the non-ionic hydrophilic methoxy poly(ethylene glycol) methacrylate (PEGMA). The architecture of the copolymers was kept constant with the hydrophobic block in the middle and the two hydrophilic blocks at the two ends, while the composition and the molecular weight of the polymers were varied. Specifically the molecular weight of the polymers was varied while the composition and the architecture were kept constant. The precursors to the polymers and the polymers were characterised in terms of their molecular weight and composition using gel permeation chromatography and proton nuclear magnetic resonance spectroscopy, respectively. Aqueous solutions of the polymers were studied by turbidimetry, hydrogen ion titration and light scattering to determine their cloud points, pKas, and hydrodynamic diameters and investigate the effect of the composition and the molecular weight of the copolymers. Finally, the thermoresponsive behaviour of the copolymers was also studied and it was found that the cloud point and gel point of the polymers were strongly affected by both the composition and molecular weight of the triblock copolymers.

Synthesis of amphiphilic ABC triblock copolymers by single electron transfer nitroxide radical coupling reaction in tetrahydrofuran

AbstractA series of ABC triblock copolymers, that is, polyisoprene‐block‐polystyrene‐block‐poly(ethylene oxide) (PI‐PS‐PEO), PI‐block‐poly(tert‐butyl acrylate)‐block‐PEO (PI‐PtBA‐PEO), and PI‐block‐poly(acrylic acide)‐block‐PEO (PI‐PAA‐PEO) were obtained by combination of anionic technique, atom transfer radical polymerization (ATRP), and single electron transfer nitroxide coupling (SETNRC) reaction. Anionic polymerization of isoprene followed by end capping with ethylene oxide yielded hydroxyl‐terminated PI. After esterification, PI with Br end group was used as a macroinitiator to initiate the polymerization of styrene and tBA by ATRP that was then trapped by 2,2,6,6‐tetramethylpiperidine‐1‐oxyl (TEMPO) group in PEO by SETNRC reaction rapidly with high efficiency in tetrahydrofuran at room temperature. The effect of reaction time and polymer chain length on SETNRC reaction was discussed in detail. In the presence of Cu0/tris[2‐(dimethylamino)ethyl]amine, SETNRC between PI‐PS‐Br and PEO‐TEMPO was carried out with the efficiency of up to 91.6% in 2 h. With the increase in polymer chain length, the efficiency decreased fleetly. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011

ABC triblock copolymers with pH-responsive LCST for controlled drug delivery

The thermo- and amphiphilic ABC triblock copolymers, single-methoxypoly(ethylene glycol)-b-poly(N-isopropylacrylamide-co-acrylic acid)-b-poly(methyl methacrylate), were synthesized by reversible addition fragmentation chain transfer radical polymerization. The triblock copolymers were characterized by Fourier transform infrared spectroscopy, 1H-NMR, and gel permeation chromatography. The copolymers self-assemble into thermo-responsive nano-sized micelles in aqueous media. Transmission electron microscopy and dynamic light scattering showed that the micelles were regularly spherical in shape with an average diameter ~120 nm. Fluorescence analysis indicated that the triblock copolymer had a low critical micelle concentration of 2.5 mg/L in aqueous media at pH 7.4 and room temperature. The lower critical solution temperature (LCST) of the micelles could be altered by simply changing the pH. The LCST of the triblock copolymer at pH 5.5 was altered to 37.5 ° C (close to physiological temperature) by copolymerizing N-isopropylacrylamide with acrylic acid. When the pH was increased to 7.4, the LCST increased to 55°C and it decreased to 33°C when the pH was 2.0. The micelles exhibited good biocompatibility with human embryonic kidney cells, when the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay was performed. The controlled release of folic acid (FA) from FA-loaded micelles under different conditions was evaluated. The rate and amount of the drug released were greater above the LCST than below it.

Vesicle Formation and Microphase Behavior of Amphiphilic ABC Triblock Copolymers in Selective Solvents: A Monte Carlo Study

Using Monte Carlo simulation, we studied the vesicle formation and microphase behavior of ABC triblock copolymers in selective solvent for A and C blocks. Simulation results show that the hydrophilicity of Blocks A and C determines not only the vesicle formation but also the microphase behavior. If Blocks A and C are of equal length, then Block A (with lower hydrophilicity) is likely to aggregate on the inner surface, whereas Block C (with higher hydrophilicity) tends to move to the outer surface, forming the ABC (from inside to outside) three-layer vesicle. Simulation results reveal that if the hydrophilicity difference between the two blocks is sufficiently low, then the ABC three layers are formed after the membrane closes (i.e., after the formation of vesicle profile). Otherwise, the ABC three layers are formed before the membrane closes. Furthermore, the effect of chain length and incompatibility between the two amphiphilic blocks (i.e., A and C) is studied and discussed in this article. The shorter block A is much more likely to aggregate on the inner surface, and the incompatibility between A and C must be sufficiently strong to ensure that the ABC copolymer forms an ABC (from inside to outside) three-layer vesicle.

Synthesis of biodegradable and biocompatible ABC triblock copolymers

AbstractA facile approach is offered to synthesize well‐defined amphiphilic ABC triblock copolymers composed of poly(ethylene glycol) monomethyl ether (MPEO) as A block, poly(L‐lysine) (PLLys) as B block, and poly(ε‐caprolactone) (PCL) as C block by a combination of ring‐opening polymerization (ROP) and click reactions. The propargyl‐terminated poly(Z‐L‐lysine)‐block‐poly(ε‐caprolactone) (MPEO‐PzLLys‐PCL) diblock copolymers were synthesized via the ring‐opening polymerization of Nε‐carbobenzoxy‐L‐lysine N‐carboxyanhydride (Z‐L‐Lys NCA) in DMF at room temperature using propargyl amine as an initiator and the resulting amino‐terminated poly(Z‐L‐lysine) then used in situ as a macroinitiator for the polymerization of ε‐caprolactone in the presence of stannous octoate as a catalyst. The triblock copolymers poly(ethylene glycol) monomethyl ether –block‐poly(Z‐L‐lysine)‐block‐poly(ε‐caprolactone) (MPEO‐PzLLys‐PCL) were synthesized via the click reaction of the propargyl‐terminated PzLLys‐PCL and azido‐terminated poly(ethylene glycol) monomethyl ether (PEO‐N3) in the presence of CuBr and 1,1,4,7,7‐pentamethyldiethylenetriamine (PMDETA) catalyst system. After the removal of Z groups of L‐lysine units, amphiphilic and biocompatible ABC triblock copolymers MPEO‐PLLys‐PCL were obtained. The structural characteristics of these ABC triblock copolymers and corresponding precursors were characterized by NMR, IR, and GPC. These results showed the click reaction was highly effective. Therefore, a facile approach is offered to synthesize amphiphilic and biocompatible ABC triblock copolymers consisting of polyether, polypeptide and polyester. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2010

Tailoring Macromolecular Expression at Polymersome Surfaces

AbstractA series of amphiphilic ABC triblock copolymers are synthesized by atom transfer radical polymerization, wherein the ‘A’ and ‘C’ blocks are hydrophilic and the pH‐sensitive ‘B’ block can be switched from hydrophilic in acidic solution to hydrophobic at pH 7. Careful addition of base to the molecularly dissolved copolymer in acidic solution readily induces the self‐assembly of such triblock copolymers at around neutral pH to form pH‐sensitive polymersomes (a.k.a. vesicles) with asymmetric membranes. By systematic variation of the relative volume fractions of the ‘A’ and ‘C’ blocks, the chemical nature of the polymer chains expressed at the interior or exterior corona of the polymersomes can be selected. Treatment of primary human dermal fibroblast cells with these asymmetric polymersomes demonstrates the biological consequences of such spatial segregation, with both polymersome cytotoxicity and endocytosis rates being dictated by the nature of the polymersome surface chemistry. The pH‐sensitive nature of the polymersomes readily facilitates their dissociation after endocytosis due to the relatively low endosomal pH, which results in the rapid release of an encapsulated dye. Selective binding of anionic substrates such as DNA within the inner cationic polymersome volume, coupled with a biocompatible exterior, leads to potential gene delivery applications for these pH‐sensitive asymmetric nanovectors.

Encapsulation of nanomaterials using an intermediary layer cross‐linkable ABC triblock copolymer

AbstractFor the preparation of core‐shell nanoparticles containing functional nanomaterials, a photo‐cross‐linkable amphiphilic ABC triblock copolymer, poly(ethylene glycol)‐b‐poly(2‐cinnamoyloxyethyl methacrylate)‐b‐poly(methyl methacrylate) (PEG‐PCEMA‐PMMA), was synthesized. This triblock copolymer was then used to encapsulate Au nanoparticles or pyrene. The triblock copolymer of PEG‐b‐poly(2‐hydroxyethyl methacrylate)‐b‐PMMA (PEG‐PHEMA‐PMMA) (Mn = 15,800 g/mol, Mw/Mn = 1.58) was first synthesized by activators generated by electron transfer atom transfer radical polymerization. Its middle block was then functionalized with cinnamoyl chloride. The degrees of polymerization of the PEG, PHEMA, and PMMA blocks were 45, 13, and 98, respectively. PMMA‐tethered Au nanoparticles (with an average diameter of 3.0 nm) or pyrene was successfully encapsulated within the PEG‐PCEMA‐PMMA micelles. The intermediary layers of the micelles were then cross‐linked by UV irradiation. The spherical structures of the PEG‐PCEMA‐PMMA micelles containing Au nanoparticles or pyrene were not changed by the photo‐cross‐linking process and they showed excellent colloidal stability. © 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 47: 4963–4970, 2009