Brush-like Copolymers Research Articles

Hyaluronan Brush-like Copolymers Promote CD44 Declustering in Breast Cancer Cells.

We report on the synthesis of hyaluronan (HA) brush-like copolymers and their application as antagonists of tumorigenic CD44-HA interactions. HA (4.8 kDa, ca. 24 saccharides) was grafted on 2-hydrohyethyl methacrylate (HEMA) by end-on oxime ligation. The obtained copolymers were compared with low and high molecular weight HA in terms of hydrolysis kinetics in the presence of hyaluronidase (isothermal titration calorimetry) and interactions with CD44 (surface plasmon resonance). The results evidenced that the high molecular weight HA and HA-g-HEMA have a much higher affinity to CD44 than low molecular weight HA. Additionally, slower enzymatic degradation was observed for the copolymer, making it an excellent candidate for active targeting of tumorigenic CD44-HA interactions. We, therefore, investigated the effect of the copolymer on cancer cell lines with different expression of CD44 and observed an efficient declustering of CD44 that is usually associated with reduction of metastasis and drug resistance.

A Nonconventional Approach toward Multihydroxy Functional Polystyrenes Relying on a Simple Grignard Reagent

Capitalizing on the inertness of styrene toward Grignard reagents, 4-vinylphenylmagnesium bromide was utilized for the rapid and convenient preparation of the protected monomer 2,2-dimethyl-4-(4-vinylbenzyl)-1,3-dioxolane (DMVBDO), avoiding the use of catalysts and painstaking purification protocols. Well-defined homopolymers, statistical copolymers, and block copolymers with styrene (S) as a comonomer were prepared in THF at −78 °C via carbanionic living polymerization. The overall molecular weights ranged from 4.5 to 68.9 kg mol–1 with low dispersities (Đ 1.04–1.15). Copolymers were synthesized with styrene feed ratios (Xfeed) from 15 to 95 mol % with glass transition temperatures (Tg) between 46 and 91 °C. Whereas polystyryllithium served as an excellent macroinitiator for the preparation of the block copolymer PS0.5-b-P(DMVBDO)0.5, the inverse block order, i.e., synthesis of P(DMVBDO)0.5-b-PS0.5, yielded a bimodal molecular weight distribution (MWD) with increased dispersity, which is ascribed to slow crossover. Rapid deprotection of both homo- and copolymers to release two hydroxyl groups per DMVBDO unit was achieved via acidic hydrolysis. The deprotected block copolymer PS0.5-b-P(VPPDO)0.5 showed phase separation, indicated by two Tg values (68 and 86 °C). Homogeneous brush copolymers of the type P(S85-co-VPPDO5)-g-PLLA and P(S85-co-VPPDO6)-g-PEO were demonstrated by using quantitative “grafting from” with l-lactide and ethylene oxide, respectively. The brush-like copolymers were obtained in quantitative yields while maintaining monodisperse MWD.

En Route to Practicality of the Polymer Grafting Technology: One-Step Interfacial Modification with Amphiphilic Molecular Brushes.

Surface modification with polymer grafting is a versatile tool for tuning the surface properties of a wide variety of materials. From a practical point of view, such a process should be readily scalable and transferable between different substrates and consist of as least number of steps as possible. To this end, a cross-linkable amphiphilic copolymer system that is able to bind covalently to surfaces and form permanently attached networks via a one-step procedure is reported here. This system consists of brushlike copolymers (molecular brushes) made of glycidyl methacrylate, poly(oligo(ethylene glycol) methyl ether methacrylate), and lauryl methacrylate, which provide the final product with tunable reactivity and balance between hydrophilicity and hydrophobicity. The detailed study of the copolymer synthesis and properties has been carried out to establish the most efficient pathway to design and tailor this amphiphilic molecular brush system for specific applications. As an example of the applications, we showed the ability to control the deposition of graphene oxide (GO) sheets on both hydrophilic and hydrophobic surfaces using GO modified with the molecular brushes. Also, the capability to tune the osteoblast cell adhesion with the copolymer-based coatings was demonstrated.

Synthesis of all-acrylic graft copolymers by grafting-through strategy in emulsion

In this paper, PnBA-g-PMMA brush-like and centipede multigraft copolymers were synthesized via DPE seeded emulsion polymerization and miniemulsion polymerization. PMMA macromonomers with single tail and double tails were prepared by DPE-technique in emulsion and Steglich esterification. Then PnBA-g-PMMA multigraft copolymers were obtained by miniemulsion copolymerization. The molecular weight and polydispersity indices of PMMA macromonomers and graft copolymers were characterized by GPC. The structural characteristics, weight content of PMMA and the number of grafting sites in brush-like and centipede multigraft copolymers were determined by 1H NMR. The thermal performance of graft copolymers were analyzed by DSC and TGA. AFM confirmed microphase separation between PnBA block and PMMA block.

Synthesis and characterization of brush-like multigraft copolymers PnBA-g-PMMA by a combination of emulsion AGET ATRP and emulsion polymerization

In this paper, poly(n-butyl acrylate)-g-poly(methyl methacrylate) multigraft copolymers were synthesized by macromonomer technique and miniemulsion copolymerization. The PMMA macromonomers were obtained by an activator generated by electron transfer atom transfer radical polymerization (AGET ATRP) in emulsion system and subsequent allylation. Then the copolymerization of different macromonomers with nBA was carried out in miniemulsion system, obtaining multigraft copolymers with high molecular weight. The latex particles and distribution of emulsion AGET ATRP and miniemulsion copolymerization were characterized using laser light scattering. The molecular weight and polydispersity indices of macromonomers and multigraft copolymers were analyzed by gel permeation chromatography, and the number-average molecular weight range is 187,600–554,800g/mol for PnBA-g-PMMA copolymers. In addition, the structural characteristics of macromonomer and brush-like copolymers were determined by infrared spectra and 1H nuclear magnetic resonance spectroscopy. The thermal performance of brush-like copolymers were characterized by differential scanning calorimetry and thermogravimetric analysis. Atomic force microscopy results showed that the degree of microphase separation was varying with increasing PMMA content in PnBA-g-PMMA. The dynamic rheometer analysis revealed that multigraft copolymer with PMMA content of 31.4% exhibited good elastomeric properties to function as a TPE. These multigraft copolymers show a promising low cost and environmental friendly thermoplastic elastomer.

One-Pot Synthesis of Brush Copolymers Bearing Stereoregular Helical Polyisocyanides as Side Chains through Tandem Catalysis

An air-stable phenylethynyl Pd(II) complex containing a polymerizable norbornene unit was designed and synthesized. Such a Pd(II) complex can initiate the living/controlled polymerization of phenyl isocyanide, giving stereoregular poly(phenyl isocyanide)s in high yields with controlled molecular weights and narrow molecular weight distributions. The norbornene unit on the Pd(II) complex can undergo ring-opening metathesis polymerization (ROMP) with Grubbs’ second-generation catalyst, affording polynorbornene bearing Pd(II) complex pendants under a living/controlled manner. Interestingly, the Pd(II) complex pendants on the isolated polynorbornene are active enough to initiate the living/controlled polymerization of phenyl isocyanides, yielding well-defined brush-like copolymers with polynorbornene backbone and helical poly(phenyl isocyanide) as side chains. 31P NMR analyses indicate almost all the Pd(II) units on the polynorbornene participated in the polymerization, and the grafting density of the brush copolymer is high. Further studies revealed the brush copolymer can be readily achieved in one-pot via tandem catalysis. By using this method, a range of brush copolymers with different structures and tunable compositions were facilely prepared in high yields with controlled molecular weights and narrow molecular weight distributions. The synthesized brush copolymers were revealed to form worm-like cylindrical morphologies and helical rod architectures in film state by atomic force microscope observations.

Fabrication of hydrophilic and sponge-like PVDF/brush-like copolymer blend membranes using triethylphosphate as solvent

Porous PVDF blend membranes with good hydrophilicity and a symmetric structure were prepared by the phase inversion method using amphiphilic brush-like copolymers, P(MMA-r-PEGMA), as hydrophilic additive and triethylphosphate (TEP) as solvent. P(MMA-r-PEGMA) was synthesized by radical polymerization in TEP. Then the obtained amphiphilic copolymer solution was mixed with PVDF and TEP to prepare the dope solution. The effects of P(MMA-r-PEGMA) content and coagulation composition on membrane morphologies were investigated using scanning electron microscopy (SEM). The results demonstrated that, even blended with amphiphilic copolymers, a symmetric structure can be formed. Hollow fiber membranes with a mainly symmetric structure were also fabricated. The dry hollow fiber membranes showed good hydrophilicity, high flux and good rejection performance because of their hydrophilic surface and pores wall.

Exploring Lubrication Regimes at the Nanoscale: Nanotribological Characterization of Silica and Polymer Brushes in Viscous Solvents

Nanotribological properties of silica surfaces, with and without adsorbed, brushlike copolymers of poly(L-lysine)-graft-poly(ethylene glycol) (PLL-g-PEG) and poly(L-lysine)-graft-dextran (PLL-g-dextran) have been investigated in aqueous viscous solvent mixtures by means of colloid-probe lateral force microscopy. Lateral forces for PEG/dextran brushes have been measured as a function of shear velocity in aqueous mixtures of glycerol and ethylene glycol (EG), which are highly miscible with water, but are poor solvents for hydrophilic PEG and dextran chains. Prior to the friction measurements on polymer brushes, a nanoscale Stribeck curve was obtained on a bare silica surface in the selected aqueous cosolvent mixtures. The Stribeck curve for bare surfaces indicates the existence of a surface-solvating thin film due to the adsorption of hydrated ions, preventing direct silica-silica contact in the boundary-lubrication regime. A clear transition to the hydrodynamic regime is seen at high speeds for solvents with higher viscosities. The polymer brushes, however, show a shear-thinning effect with increasing shear speed and a combined influence of polymer film and solvent viscosity on the measured friction forces. The formation of an interfacial fluid-film is shown to shift the hydrodynamic regime of hydrated brushes to a lower value of Uη. The correlation between the structural configuration and the corresponding frictional properties of the polymer brushes upon changing solvent quality is discussed.

Synthesis and versatile postpolymerization modification of couplable A(BC)mD heterografted comblike block quaterpolymers

The synthesis and postfunctionalization of A(BC)mD (A = PDMA; B = PEG; C = PCL; D = PNIPAM, PtBA and PMA) comblike block copolymers comprising alkyne and tertiary amino functionalities and alternating PEG and PCL grafts are described. Three-step successive RAFT processes using prop-2-ynyl 4-(benzodithioyl)-4-cyanopentanoate as an original mediator were used to synthesize amphiphilic PDMA(PEG-alt-PCL)mPM (m ≈ 7) heterografted copolymers, in which the PEG and PCL segments were introduced by the alternating copolymerization of styrenic and maleimidic macromonomers. GPC-MALLS and 1H NMR results indicated that the resultant quaterpolymers were of well-controlled molecular weight and relatively low polydispersity (PDI = 1.12–1.25). The combination of end group transformation and the azide–alkyne “click” reaction afforded (A(BC)mD)n (n ≈ 4) comblike-linear multiblock copolymer and (A(BC)mD)x (x ≈ 7) dendritic graft copolymer, and Menschutkin reaction between A(BC)mD copolymer and bromide-functionalized small molecule/macromolecule gave an ion-bearing A′(BC)mD comblike block copolymer and A(BC)mD-graft-E toothbrushlike copolymer, revealing the great potential of postpolymerization modification in novel architecture construction. Preliminary results indicated that the introduction of various functionalities and polymer segments into brushlike copolymers via the quaternization process could affect the chain relaxation and melting behaviors, solubility, and surface wettability of polymer films.

Amphiphilic Brush-Like Copolymers Involving Hydrophobic Amino Acid- and Oligopeptide-Side Chains for Optical Tumor Imaging In Vivo

Abstract Amphiphilic brush-like copolymers having simple amino acids or oligopeptides and poly(ethylene glycol) as side chains were synthesized via ring-opening metathesis polymerization and further transformations. All of the synthesized copolymers formed spherical self-assemblies in water and their hydrodynamic diameters were 100–250 nm, as measured by dynamic light scattering. Amphiphilic polymers bearing leucine and valine can form stable spherical self-assemblies in water because of the synergistic effects of intermolecular hydrogen bonding and hydrophobic interaction. The oligomerization of leucine moieties and capping with the proper length of fatty acyl groups at an N-terminus could significantly affect both the stability and fluorescence intensity of near-infrared fluorescent (NIRF) dye-containing polymeric self-assemblies. All of the self-assemblies consisting of leucine- and oligoleucine-grafted copolymers with a NIRF indocyanine green dye and hydrophilic targeting agents showed low cytotoxicity in cell viability tests. Furthermore, self-assemblies consisting of N-acetylleucine-grafted copolymers with strong fluorescence could visualize a tumor site with high-contrast in vivo, while low contrast images were obtained by utilizing oligoleucine-grafted self-assemblies because of their weak fluorescence. These results indicate that the precise control of both the number of leucine moieties and the length of the fatty acyl groups is important to produce highly functionalized tumor-targeting vehicles delivering a NIRF dye.

Influence of Side Chain Length on Fluorescence Intensity of ROMP‐Based Polymeric Nanoparticles and Their Tumor Specificity in In‐Vivo Tumor Imaging

In this study, amphiphilic brush-like copolymers conjugated with short alkyl or long polymeric chains of various lengths are synthesized using ring-opening metathesis polymerization (ROMP) of substituted norbornadiene monomers followed by chemical transformations. These amphiphilic copolymers form spherical self-assemblies in aqueous media with diameters of 132-244 nm. The low critical aggregation concentration of these assemblies (2.5 × 10(-3) -1.4 × 10(-5) g/L) indicates that they are quite stable in dilute conditions. An appropriate length of polymer side chain that conjugates the polymer backbone with a hydrophobic ICG (indocyanine green) moiety enhanced the fluorescence intensities of these self-assemblies in aqueous solution as well as in tumor-bearing mice. A longer side chain conjugated with tumor targeting agents could significantly affect the tumor specificity of self-assemblies to a greater extent. The self-assemblies bearing hydrophilic tumor targeting agents, such as a glucosamine molecule and a cyclic RGD (arginine-glycine-asparatic acid) peptide, accumulated in tumor tissues with high selectivity, while those having a hydrophobic targeting agent, such as folate moieties, accumulated in tumor sites with low selectivity. The results demonstrated here unambiguously indicate that the fluorescence intensity and tumor specificity of self-assemblies are strongly affected by the length of side chains that conjugate with dyes and targeting agents.

Synthesis of brush-like copolymers using carbohydrates as initiators: Benefits of organic catalysts for the ROP of lactones

New brush-like copolymers have been synthesized using functional polymethacrylate backbones bearing pendant sugars. Ring-opening polymerization (ROP) of l-lactide and ε-caprolactone have been performed using 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) and 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD) carbohydrate residues on the polymethacrylate chains. The latter have been first synthesized by copolymerization of three methacrylate monomers including methyl methacrylate (MMA), α-methoxy, ω-methacrylate poly(ethylene oxide) (MAPEO), and 1,2:3,4-di-O-isopropylidene-6-O-methacryloyl- d-galactopyranose (MAIGP) by atom transfer radical polymerization (ATRP) in toluene at 80 °C using CuBr ligated with 1,1,4,7,10,10 hexamethyltriethylenetetramine (HMTETA) as catalytic complex. The protected sugars have been selectively deprotected using an aqueous solution of formic acid. The molecular characterization of those copolymers was performed by 1H-NMR spectroscopy, FT-IR spectroscopy and gel permeation chromatography (GPC) analysis.

Synthesis and characterization of block copolymers comprising a polyrotaxane middle block flanked by two brush-like PCL blocks

A polyrotaxane was prepared via atom transfer radical polymerization (ATRP) of 2-hydroxyethyl methacrylate (HEMA) initiated by a polypseudorotaxane self-assembled from a distal 2-bromoisobutyryl end-capped poly(ethylene glycol) (BriB–PEG–iBBr) with α-cyclodextrins (α-CDs). Then it was used to initiate bulk ring-opening polymerization (ROP) of e-caprolactone (CL) to give block copolymers comprising a polyrotaxane middle block flanked by two brush-like polycaprolactone (PCL) blocks. The structure of both the polyrotaxane and its CL derivatives was characterized by 1H NMR, GPC, FT-IR, XRD, DSC and TG analyses. These polyrotaxane-derived block brush-like copolymers can be cast into self-standing films from CH2Cl2 and self-assemble into nano-sized particles in THF as well. Furthermore they can melt at round 60 °C, showing the potential for melt-processing.