Syntheses and characterizations of the multiple morphologies formed by the self-assembly of the semicrystalline P4VP-b-PCL diblock copolymers

A series of semicrystalline diblock copolymers of poly(4-vinylpyridine-b-?-caprolactone) (P4VP-b-PCL) have been synthesized by the living ROP of CL followed by the TEMPO polymerization of 4-VP. Depending on the relative block length and different solvent compositions, these copolymers self-assemble into different supramolecular structures in toluene/dichloromethane (DCM) solution, including spherical micelles, bowl-shaped vesicles, multilayer vesicles, porous spheres, and large compound micelles. In methanol/DCM solution system, the crystalline PCL core disturbs the balance of free energy, thus results in a series of morphological changes including spherical micelles, worm-like rods, vesicles, coexisted vesicles and lamella, and finally platelet lamella.     

Self-assembly behavior of rod–coil–rod polypeptide block copolymers

Self-assembly behavior of rod–coil–rod poly(γ-benzyl-l-glutamate)-b-poly(ethylene glycol)-b-poly(γ-benzyl-l-glutamate) (PBLG-b-PEG-b-PBLG) triblock copolymers with various PBLG block lengths in aqueous solution was investigated. The PBLG-b-PEG-b-PBLG triblock copolymers are able to self-assemble into vesicles when PBLG block length is relatively short. Meanwhile, the initial polymer concentration was found to have influence on the self-assembly. Giant vesicles can be observed when the initial concentration is high. Dissipative particle dynamics (DPD) simulations about the vesicles revealed that the rigid rod blocks could be aligned parallelly with each other to form the monolayer vesicles wall. When the PBLG block length in the PBLG-b-PEG-b-PBLG triblock copolymers increases, the aggregate morphologies were observed to transform from vesicles to spherical micelles. Based on the experimental and simulation results, we proposed a possible mechanism of the morphological transitions of the rod–coil–rod triblock copolymer aggregates.     

Selective distribution of interacting magnetic nanoparticles into block copolymer domains based on the facile inversion of micelles

We demonstrate a simple methodology to incorporate interacting magnetic nanoparticles (mNPs) into cylinder forming block copolymer templates. Poly(styrene-block-isoprene) (PS-b-PI) with PI cylinders and poly(styrene-block-4vinylpyridine) (PS-b-P4VP) with PS cylinders were used as the block copolymer templates and γ-Fe₂O₃ NPs coated with oleic acids were pre-synthesized for the interacting mNPs. Regardless of the template block copolymers, the selective location of mNPs and the size of mNP aggregates are clearly altered by changing casting solvents. When good solvents for both blocks were used as casting solvents, mNPs are readily aggregated during the solvent evaporation. In contrast, under selective casting solvents for the minor blocks, the mNPs were selectively trapped into the cylinder domains through the facile inversion of micelles during solvent evaporation. The interplay between mNPs and block copolymers was also tested with different molecular weights of block copolymers.     

Association behavior of thermo-responsive block copolymers based on poly(vinyl ethers)

Thermo-sensitive nanosized structures have been prepared in water from poly(methyl vinyl ether)-block-poly(isobutyl vinyl ether) (PMVE-b-PIBVE) block copolymers. The composition and the architecture (diblock and triblock architectures) of the PMVE-b-PIBVE copolymers have been varied. The investigated copolymers had an asymmetric composition with a major PMVE block. While the PIBVE blocks are hydrophobic, the PMVE blocks are hydrophilic at room temperature and become hydrophobic above their demixing temperature (around 36 °C) as a result of the lower critical solution temperature (LCST) behavior. At room temperature, the amphiphilic copolymers aggregate in water above a critical micelle concentration, which has been experimentally measured by hydrophobic dye solubilization. The hydrodynamic diameter of the structures formed above the cmc has been measured by dynamic light scattering (DLS) while their morphology has been studied by transmission electron microscopy (TEM). ¹H NMR measurements in D₂O at room temperature reveal that the aggregates contain PIBVE insoluble regions surrounded by solvated PMVE chains. These investigations have shown that polydisperse spherical micelles are formed for asymmetric PMVE-b-PIBVE copolymers containing at least 9 IBVE units. For copolymers containing less IBVE units, loose aggregates are formed.Finally, the thermo-responsive, reversible properties of these structures have been investigated. Above the cloud point of the copolymers, the loose aggregates precipitate while the micelles form large spherical structures.     

Design and stabilization of block copolymer micelles via phenol-pyridine hydrogen-bonding interactions

A new approach for the preparation of block copolymer micelles in non-selective solvent is introduced. Phenol-pyridine hydrogen-bonding interactions are used for the first time to prepare core-shell micelles in non-selective solvents using block copolymers and bifunctional low-molecular-weight hydrogen-bonding crosslinkers. Poly(styrene-b-4-vinylphenol)/Bis-pyridyl ethane and poly(styrene-b-4-vinylpyridine)/Bisphenol A were investigated as micelle formation due to phenol-pyridine hydrogen bond crosslinking. The influence of several factors such as temperature, concentration, solvent and pH in micellization-demicellization process was analyzed by Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), dynamic light scattering (DLS) and atomic force microscopy (AFM). This method opens new possibilities to the generation of block copolymer micelles in non-selective solvents.     

Effects of micelle structures formed in selective solvents on crystallization behaviors of poly(ethylene glycol)-b-poly(styrene) copolymers

Well-defined amphiphilic block copolymers, poly(ethylene glycol) methyl ether-b-poly(styrene) (mPEG-b-PS), in which the PS blocks had different molecular weights, were synthesized by atom transfer radical polymerization (ATRP). Through introduction of selective solvents for the blocks, crystalline and amorphous blocks were self-assembled into different micelle structures in solutions. Atomic force microscopy (AFM) was used to characterize the micelle structures. It was observed that spherical micelles were always formed, whereas lamellar aggregates appeared only in the PS-selective solvent when the molecular weight of the PS block in mPEG-b-PS was low. The crystallizable mPEG blocks were self-assembled into either the core or corona of the micelles formed. The effects of the self-assembled structures on the crystallization behavior of mPEG blocks were then investigated with differential scanning calorimeter (DSC). When the PS molecular weight was much larger than that of mPEG, the result showed that the crystallinity of the mPEG block was lower when mPEG blocks crystallized in the corona than that in the core of the micelles. In this case, when mPEG blocks crystallized in micelle coronae, the micelle core formed by insoluble PS blocks was very big, so mPEG chains had to distribute sparsely in the micelle coronae. It was hard for mPEG chains in one micelle or among different micelles to gather together to crystallize. However, when the PS molecular weight was lower than that of mPEG, the crystallinity of mPEG was higher when the mPEG chains crystallized in the micelle corona, as the core formed by insoluble PS was small and the mPEG chains in the corona were easy to aggregate and crystallize.     

Poly(N-tert-butyl acrylamide-b-N-acryloylmorpholine) amphiphilic block copolymers via RAFT polymerization: Synthesis, purification and characterization

Amphiphilic block copolymers consisting of two poly(acrylamide) derivative blocks have been synthesized via the reversible addition fragmentation chain transfer (RAFT) polymerization process with a hydrophobic block, poly(N-tert-butyl acrylamide), poly(TBAm), and a non-ionic hydrophilic one, poly(N-acryloylmorpholine), poly(NAM). Both polymerization orders, poly(TBAm-b-NAM) and poly(NAM-b-TBAm), were compared in terms of conversion and control over molecular weights (MW). Purification of the block copolymers was carried out via several methods in order to optimize their subsequent characterization. ¹H NMR analysis resulted in an accurate determination of the second block MW whereas determination of the CMC by the pendant drop method confirmed the ability of the poly(TBAm-b-NAM) block copolymers to self-assemble into micelles in aqueous phase.     

Long-tailed spherical aggregates formed from ABA triblock copolymer by changing the properties of selective solvent

A convenient method of tuning aggregate morphologies from amphiphilic block copolymer by adding second selective solvent is introduced in this paper. Some novel aggregate morphologies, i.e. hierarchical vesicles (and compound spherical micelles) with one or more tails, were formed by introducing a second selective solvent for core-forming blocks into the poly(4-vinyl pyridine)-b-polystyrene-b-poly(4-vinyl pyridine) ABA amphiphilic block copolymer/co-solvent/water systems. Addition of selective solvent (toluene) for core-forming blocks (PS blocks) has significant effect on the aggregate morphologies from the amphiphilic triblock copolymer. The aggregate morphologies changed from spheres to rods, long tailed solid large compound spheres, and to long tailed hierarchical vesicles by adding 0.5, 10 and 30 wt% of toluene to the organic solvent, respectively. There exists an aggregate morphological transition of the long tailed hierarchical vesicles to long tailed solid spheres by decreasing the content of toluene in the organic solvent mixture. The tails disappeared, and irregular vesicular and spherical structures were formed when the toluene content was 20 wt%. The toluene addition is expected to increase the stretching of the core-forming blocks (PS), and to modify the interfacial tension of core-corona interface, which are the main reasons for the aggregate morphology transition. To the best of our knowledge, these tailed vesicles and spherical morphologies have not been found in block copolymer aggregates system up to now.     

Self-assembly of POSS-containing block copolymers: Fixing the hierarchical structure in networks

A series of P(MMA-co-GMA)-b-PMAPOSS block copolymers (BCPs) were synthesized by ATRP. The BCPs contain POSS (polyhedral oligomeric silsesquioxane) as a pendant unit on a particular polymer block chain. In selective solvents, the BCPs self-assemble to form ordered micellar-like structures. Spherical, cylindrical or vesicle-like morphologies were produced by tuning the BCP and mixed solvent compositions. Crosslinking of the BCP by the reaction of the glycidyl groups in the P(MMA-co-GMA) block of the micelle shell (GMA = glycidyl methacrylate) with a diamine results in a long-range structure ordering. The hexagonally packed cylindrical arrangement of the BCP networks was revealed by SAXS and TEM. The hierarchical, ordered structure of the POSS-containing hybrids was fixed by crosslinking. In addition, transient physical gels were prepared from triblock copolymers with outer MAPOSS blocks, and their rheological behavior was investigated.     

Micellar morphologies of self-associated diblock copolymers in acetone solution

We describe the synthesis and solution morphologies of poly(vinyl phenol-b-styrene) (PVPh-b-PS) micelles and the effects that changing the copolymer composition and concentration have on self-assembly structures of PVPh-b-PS in acetone (a good solvent for PVPh). These PVPh-b-PS copolymers aggregated into spherical, rod-like, and vesicular morphologies. The transformations of the PVPh-b-PS block copolymer micelles in acetone depended on a number of parameters, including the relative block lengths, their concentrations, and the degree of self-association through hydrogen bonding of the coronal PVPh chains. We also investigated the morphologies of the micelles formed from acetone solutions of poly(4-tert-butoxystyrene-b-styrene) (PtBOS-b-PS) copolymers having the same degree of polymerization as the precursor of PVPh-b-PS copolymer before hydrolysis reaction. Our results indicate that the micelles formed from PVPh-b-PS copolymers in acetone were more complicated than those prepared from PtBOS-b-PS copolymers in acetone because hydrogen bonding occurs in the micelle corona of the PVPh block. Finally, we also discussed the morphology transition when the self-association hydrogen bonding of PVPh block was destroyed by adding proton acceptor poly(4-vinylpyridine) (P4VP).     

双亲性聚合物胶束研究进展

两亲性嵌段聚合物在选择性溶剂中可以自组装成为一系列的形态结构,如球状胶束、柱状胶束、层状胶束、囊泡和微管结构,尤其自组装形成胶束,这一结构可做为药物输送材料已成为高分子科学和生物医学研究领域的热点之一。文章对上述领域进行综述,结合作者研究的课题,分成三大类进行阐述：胶束的制备方法;影响胶束的因素;胶束的表征方法。     

Preparation and self-assembly of double hydrophilic poly(ethylethylene phosphate)-block-poly[2-(succinyloxy)ethyl methacrylate] diblock copolymers for drug delivery

This work focuses on the synthesis and self-assembly of biodegradable and anionic double hydrophilic diblock copolymers (DHBCs) poly(ethylethylene phosphate)-block-poly[2-(succinyloxy)ethyl methacrylate] (PEEP-b-PSEMA) with different molecular weights and compositions, which were prepared via a combination of ring opening polymerization (ROP), atom transfer radical polymerization (ATRP) and polymer reaction. The chemical structures of these well-defined diblock copolymers were confirmed by ¹H NMR and FT-IR analyses. GPC results indicated that the copolymers showed symmetric peak and relatively narrow polydispersities. Subsequently, pH-responsive micellization behaviors of PEEP-b-PSEMA diblock copolymers were investigated by fluorescence probe method, dynamic light scattering (DLS) and transmission electron microscopy (TEM) measurements. The results demonstrated that these diblock copolymers were able to self-assemble into micelles with various sizes depending on the variation of pH values. Naproxen (NAP), a poorly water-soluble drug, was selected as the model drug and encapsulated into the core of micelles via dialysis method. The in vitro release behavior of NAP from these micelles was pH-dependent and could be accelerated in the presence of phosphodiesterase I which could promote the degradation of polyphosphoesters. Cytotoxicity tests by MTT assay showed that these block copolymers possessed favorable biocompatibility against HeLa cells, revealing that this kind of biodegradable, biocompatible and pH-responsive block copolymer would be served as a promising material for drug delivery.     

Self-assembly of amphiphilic liquid crystal block copolymers containing a cholesteryl mesogen: Effects of block ratio and solvent

We report on the self-assembly, in water and in bulk, of amphiphilic liquid crystal block copolymers consisting of a cholesterol-based smectic LC polymer block (PAChol) and poly(ethylene glycol) (PEG) block. Two series of block copolymers, PEG₄₅-b-PAChol and PEG₁₁₄-b-PAChol (45 and 114 are the degree of polymerization of PEG blocks) with different hydrophilic/hydrophobic weight ratios were synthesized and characterized in detail. Depending on the diblock composition, smectic polymer vesicles and/or nanofibers were formed by adding water into a dilute solution of copolymers in dioxane. If THF is used instead of dioxane as solvent, solid spherical aggregates were obtained upon water addition for PEG₄₅-b-PAChol series, while macroscopic precipitation occurred for PEG₁₁₄-b-PAChol series. The mesomorphic and microphase segregation structures of the block copolymers in bulk were studied by X-ray scattering, DSC and POM. The interdigital smectic A (SmA_d) phase with a lamellar period of 4.25 nm was detected in all block copolymers. For PEG₁₁₄-b-PAChol₅ (PEG/PAChol weight ratio = 66/34) and PEG₁₁₄-b-PAChol₁₂ (45/55), lamellar type of microphase segregation was observed.     

Self-assembly of block copolymer complexes in organic solvents

Micelles have been prepared by mixing poly(styrene)-block-poly(4-vinylpyridine) (PS-b-P4VP) copolymers and poly(acrylic acid) (PAA) homopolymers in organic solvents. Complexation via hydrogen bonding occurs between the P4VP and PAA blocks. Further aggregation of the accordingly formed complexes results in micelles stabilized by a corona of PS blocks. The influence of the relative lengths of the different blocks and of the quality of the solvent towards the complexes on the micellar characteristic features is studied. Soluble, non-aggregating, complexes have been observed in DMF, provided that the complexes are sufficiently small. In all other cases, the complexes were insoluble and aggregated in micelles. The size of those micelles depends strongly on the length of the P4VP blocks but only weakly on the PAA length.     

Synthesis and characterization of temperature and pH-responsive pentablock copolymers

A family of amphiphilic ABCBA pentablock copolymers based on commercially available Pluronic^® F127 block copolymers and various amine containing methacrylate monomers was synthesized via Cu(I) mediated controlled radical polymerization. The block architecture and chemical composition of the pentablock copolymers were engineered to exhibit both temperature and pH responsive self-assembly by exploiting the lower critical solution temperature of the poly(ethylene oxide)/poly(propylene oxide) blocks and the polycationic property of the poly(amine methacrylate) blocks, respectively. In aqueous solutions, the pentablock copolymers formed temperature and pH-responsive micelles. Concentrated aqueous solutions of the copolymer formed a pH-responsive, thermoreversible gel phase. The controlled radical synthesis route yielded well-defined copolymers with narrow molecular weight distributions with the benefit of mild reaction conditions. Small angle X-ray scattering, laser light scattering, cryogenic transmission electron microscopy and dynamic mechanical analysis have been used to characterize the self-assembled structures of the micellar solution and gel phases of the aqueous copolymer system. These copolymers have potential applications in controlled drug delivery and non-viral gene therapy due to their tunable phase behavior and biocompatibility.     

Direct preparation of vesicles from one-pot RAFT dispersion polymerization

Various morphologies including spherical micelles, nanowires and vesicles have been prepared by reversible addition-fragmentation chain transfer (RAFT) dispersion polymerization of styrene (St) in methanol using S-1-dodecyl-S -(α,α′-dimethyl-α″-acetic acid) trithiocarbonate (TC)-terminated poly(ethylene oxide) (PEO-TC) and 2,2′-azobis(isobutyronitrile) (AIBN) as chain transfer agent and initiator, respectively. GPC, ¹H NMR, TEM and laser light scattering (LLS) were used to track the polymerization. The results showed that the block copolymers PEO-b-polystyrene (PEO-b-PS) were formed firstly in homogenous polymer solution, and then the spherical micelles were produced via polymerization-induced self-assembling. Continuous polymerization of the PS blocks induced the transition of spherical micelles into other morphologies. The polymerization-induced self-assembling and reorganization (PISR) were induced by chain length ratio increase of PS to PEO blocks. The concentration of St in methanol is also important factor to influence the formation of morphologies.     

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.     

Chaperone-like α-cyclodextrins assisted self-assembly of double hydrophilic block copolymers in aqueous medium

Chaperones are defined as a family of protein that mediates the correct assembly of other polypeptides but that are not components of the functional assembled structures. In this work, we have devised a novel method in which α-cyclodextrins (α-CDs), “artificial chaperones”, facilitate block copolymers self-assembling into the expected structure. Poly(ethylene oxide)-b-poly(4-vinylpyridine) (PEO₄₅-b-P4VP₇₀) is first threaded by α-CDs, leading to the formation of metastable micelles. After stabilizing the metastable micelles by shell cross-linking with poly(ethylene oxide)-b-poly(acrylic acid) (PEO₁₁₄-b-PAA₅₀), α-CDs are removed and the expected structure, polymeric vesicle, is achieved. On the contrary, only spherical micelles are formed in the similar conditions without the assistance of α-CD. Therefore, α-CDs, which act as chaperones, guide the self-assembly of block copolymers in the expected pathway.     

Functionalization of amphiphilic coil-rod-coil triblock copolymer poly(2-vinylpyridine)-b-poly(n-hexyl isocyanate)-b-poly(2-vinylpyridine) with florescence moiety and C60

We recently achieved quantitative synthesis of an amphiphilic coil-rod-coil triblock copolymer, poly(2-vinylpyridine)-b-poly(n-hexyl isocyanate)-b-poly(2-vinylpyridine), by coupling in situ living diblock copolymer poly(2-vinylpyridine)-b-poly(n-hexyl isocyanate) (P2VP-b-PHIC) using malonyl chloride in the presence of pyridine. This led to the introduction of an active methylene group that is a site for further functionalization in the rod block. The Michael addition reaction of the triblock copolymer with 7-(4-trifluoromethyl) coumarin acrylamide led to copolymer bearing a fluorescent pendent in the rod block. The fluorescent labeled copolymers were isolated in ∼94% yields. Similarly C₆₀ pendent was introduced to the rod block by the Bingel reaction. The yields of C₆₀ functionalized copolymers were ∼54%. The precursor and functionalized amphiphilic coil-rod-coil copolymer show diverse morphologies, such as micelles and vesicles by simply changing the solvent. For the C₆₀ functionalized block copolymer, structural constraints in micelles and vesicles prevented C₆₀ pendents to aggregate.     

Synthesis of ABA triblock copolymer of poly(potassium acrylate-styrene-potassium acrylate) by atom transfer radical polymerization and the self-assembly in selective solvents

A series of well-defined ABA triblock copolymers of poly(methyl acrylate)-polystyrene-poly(methyl acrylate) (PMA-b-PS-b-PMA) with different molecular weights were synthesized using Cl-PS-Cl as macroinitiator, CuCl/N,N,N′,N″,N″-pentamethyldiethylenetriamine (PMDETA) as catalyst system via atom transfer radical polymerization (ATRP). Amphiphilic triblock copolymer poly(potassium acrylate)-polystyrene-poly(potassium acrylate) (PKAA-b-PS-b-PKAA) was obtained by hydrolyzing PMA-b-PS-b-PMA. The self-assembly behavior of the triblock copolymers in organic solutions, which is a good solvent for the PS block and in aqueous solutions, which is a good solvent for the PKAA blocks was studied by high performance particle sizer (HPPS). The results showed that the Z-average size of the micelles obviously increases with increase in molecular weight of triblock copolymers, and the micelles in organic solutions are relatively more stable than in aqueous solutions. The effect of the length of PS block on the Z-average size of the micelles is more obvious in organic solution than in aqueous solution. The morphology of triblock copolymers PKAA-b-PS-b-PKAA in aqueous solution, which is a nearly ‘pearl-necklace’-like shape, was examined by transmission electron microscopy (TEM) at room temperature.