Dual‐responsive copolymer poly(2,2,3,4,4,4‐hexafluorobutyl methacrylate)‐block‐poly[2‐(dimethylamino)ethyl methacrylate] synthesized via photoATRP for surface with tunable wettability

In this work, a series of block copolymers of poly(2,2,3,4,4,4‐hexafluorobutyl methacrylate)‐block‐poly[2‐(dimethylamino)ethyl methacrylate] (PHFBMA‐b‐PDMAEMA) were synthesized via photo‐induced atom transfer radical polymerization (photoATRP) at room temperature. By the introduction of PDMAEMA segment, the hydrophilicity of the silicon wafer surface spin‐coated with PHFBMA homopolymer was improved. Furthermore, the study of tunable surface wettability showed that the surface wettability was pH‐dependent and thermal‐independent at pH 2 and 10. The as‐fabricated surface coated with PHFBMA₁₁₀‐b‐PDMAEMA₁₈₇ showed switchable water contact angle from 85.4° at pH > 4 to 55.0° at pH 2 due to the protonation and deprotonation of tertiary amine groups of PDMAEMA. However, because of the ascendancy of protonated PDMAEMA at pH 2 and the decreased LCST at pH 10, the wettability of the as‐prepared surfaces was thermal‐insensitive. Finally, surface morphology and composition investigation showed that the property of wettability‐controllable surface was not only influenced by surface composition, but also affected by chain conformation. © 2016 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016 , 54, 3868–3877     

Self‐assembly of thermo‐ and pH‐responsive poly(acrylic acid)‐b‐poly(N‐isopropylacrylamide) micelles for drug delivery

Self‐assembled thermo‐ and pH‐responsive poly(acrylic acid)‐b‐poly(N‐isopropylacrylamide) (PAA‐b‐PNIPAM) micelles for entrapment and release of doxorubicin (DOX) was described. Block copolymer PAA‐b‐PNIPAM associated into core‐shell micelles in aqueous solution with collapsed PNIPAM block or protonated PAA block as the core on changing temperature or pH. Complexation of DOX with PAA‐b‐PNIPAM triggered by the electrostatic interaction and release of DOX from the complexes due to the changing of pH or temperature were studied. Complex micelles incorporated with DOX exhibited pH‐responsive and thermoresponsive drug release profile. The release of DOX from micelles was suppressed at pH 7.2 and accelerated at pH 4.0 due to the protonation of carboxyl groups. Furthermore, the cumulative release of DOX from complex micelles was enhanced around LCST ascribed to the structure deformation of the micelles. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 5028–5035, 2008     

Synthesis and characterization of PNIPAM‐b‐(PEA‐g‐PDEA) double hydrophilic graft copolymer

A series of well‐defined double hydrophilic graft copolymers, consisting of poly(N‐isopropylacrylamide)‐b‐poly(ethyl acrylate) (PNIPAM‐b‐PEA) backbone and poly(2‐(diethylamino)ethyl methacrylate) (PDEA) side chains, were synthesized by successive atom transfer radical polymerization (ATRP). The backbone was firstly prepared by sequential ATRP of N‐isopropylacrylamide and 2‐hydroxyethyl acrylate at 25 °C using CuCl/tris(2‐(dimethylamino)ethyl)amine as catalytic system. The obtained diblock copolymer was transformed into macroinitiator by reacting with 2‐chloropropionyl chloride. Next, grafting‐from strategy was employed for the synthesis of poly(N‐isopropylacrylamide)‐b‐[poly(ethyl acrylate)‐g‐poly(2‐(diethylamino)ethyl methacrylate)] (PNIPAM‐b‐(PEA‐g‐PDEA)) double hydrophilic graft copolymer. ATRP of 2‐(diethylamino)ethyl methacrylate was initiated by the macroinitiator at 40 °C using CuCl/hexamethyldiethylenetriamine as catalytic system. The molecular weight distributions of double hydrophilic graft copolymers kept narrow. Thermo‐ and pH‐responsive micellization behaviors were investigated by fluorescence spectroscopy, ¹H NMR, dynamic light scattering, and transmission electron microscopy. Unimolecular micelles with PNIPAM‐core formed in acidic environment (pH = 2) with elevated temperature (≥32 °C); whereas, the aggregates turned into vesicles in basic surroundings (pH ≥ 7.2) at room temperature. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 5638–5651, 2008     

Effect of polystyrene‐b‐poly(ethylene oxide) on self‐assembly of polystyrene‐b‐poly(N‐isopropylacrylamide) in aqueous solution

Mixed micelles of polystyrene‐b‐poly(N‐isopropylacrylamide) (PS‐b‐PNIPAM) and two polystyrene‐b‐poly(ethylene oxide) diblock copolymers (PS‐b‐PEO) with different chain lengths of polystyrene in aqueous solution were prepared by adding the tetrahydrofuran solutions dropwise into an excess of water. The formation and stabilization of the resultant mixed micelles were characterized by using a combination of static and dynamic light scattering. Increasing the initial concentration of PS‐b‐PEO in THF led to a decrease in the size and the weight average molar mass (〈M_w〉) of the mixed micelles when the initial concentration of PS‐b‐ PNIPAM was kept as 1 × 10^?3 g/mL. The PS‐b‐PEO with shorter PS block has a more pronounced effect on the change of the size and 〈M_w〉 than that with longer PS block. The number of PS‐b‐PNIPAM in each mixed micelle decreased with the addition of PS‐b‐PEO. The average hydrodynamic radius 〈R_h〉 and average radius of gyration 〈R_g〉 of pure PS‐b‐PNIPAM and mixed micelles gradually decreased with the increase in the temperature. Both the pure micelles and mixed micelles were stable in the temperature range of 18 °C–39 °C. © 2010 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 48: 1168–1174, 2010     

Aqueous RAFT polymerization of N‐isopropylacrylamide‐mediated with hydrophilic macro‐RAFT agent: Homogeneous or heterogeneous polymerization?

Aqueous RAFT polymerization of N‐isopropylacrylamide (NIPAM) mediated with hydrophilic macro‐RAFT agent is generally used to prepare poly(N‐isopropylacrylamide) (PNIPAM)‐based block copolymer. Because of the phase transition temperature of the block copolymer in water being dependent on the chain length of the PNIPAM block, the aqueous RAFT polymerization is much more complex than expected. Herein, the aqueous RAFT polymerization of NIPAM in the presence of the hydrophilic macro‐RAFT agent of poly(dimethylacrylamide) trithiocarbonate is studied and compared with the homogeneous solution RAFT polymerization. This aqueous RAFT polymerization leads to the well‐defined poly(dimethylacrylamide)‐b‐poly(N‐isopropylacrylamide)‐b‐poly(dimethylacrylamide) (PDMA‐b‐PNIPAM‐b‐PDMA) triblock copolymer. It is found, when the triblock copolymer contains a short PNIPAM block, the aqueous RAFT polymerization undergoes just like the homogeneous one; whereas when the triblock copolymer contains a long PNIPAM block, both the initial homogeneous polymerization and the subsequent dispersion polymerization are involved and the two‐stage ln([M]_o/[M])‐time plots are indicated. The reason that the PNIPAM chain length greatly affects the aqueous RAFT polymerization is discussed. The present study is anticipated to be helpful to understand the chain extension of thermoresponsive block copolymer during aqueous RAFT polymerization. © 2013 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2013     

Doubly thermoresponsive brush‐linear‐linear ABC triblock copolymer nanoparticles prepared through dispersion RAFT polymerization

Doubly thermoresponsive ABC brush‐linear‐linear triblock copolymer nanoparticles of poly[poly(ethylene glycol) methyl ether vinylphenyl]‐block‐poly(N‐isopropylacrylamide)‐block‐polystyrene [P(mPEGV)‐b‐PNIPAM‐b‐PS] containing two thermoresponsive blocks of poly[poly(ethylene glycol) methyl ether vinylphenyl] [P(mPEGV)] and poly(N‐isopropylacrylamide) (PNIPAM) are prepared by macro‐RAFT agent mediated dispersion polymerization. The P(mPEGV)‐b‐PNIPAM‐b‐PS nanoparticles exhibit two separate lower critical solution temperatures or phase‐transition temperatures (PTTs) corresponding to the linear PNIPAM block and the brush P(mPEGV) block in water. Upon temperature increasing above the first and then the second PTT, the hydrodynamic diameter (D_h) of the triblock copolymer nanoparticles undergoes an initial shrinkage at the first PTT and the subsequent shrinkage at the second PTT. The effect of the chain length of the PNIPAM block on the thermoresponsive behavior of the triblock copolymer nanoparticles is investigated. It is found that, the longer chains of the thermoresponsive PNIPAM block, the greater contribution on the transmittance change of the aqueous dispersion of the triblock copolymer nanoparticles. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2014 , 52, 2266–2278     

Triple stimuli‐responsive amphiphilic glycopolymer

Triple stimuli (temperature/pH/photo)‐responsive amphiphilic glycopolymer, poly(2‐(dimethylamino)ethyl methacrylate‐co‐6‐O‐methacryloyl‐1,2,3,4‐di‐O‐isopropylidene‐D‐galactopyranose)‐b‐poly(4‐(4‐methoxyphenylazo)phenoxy methacrylate) [P(DMAEMA‐co‐MAIpGP)‐b‐PMAZO] was synthesized by atom transfer radical polymerization, followed by the hydrolysis of MAIpGP groups, resulting in the target product poly(2‐(dimethylamino)ethyl methacrylate‐co‐6‐O‐methacryloyl‐D‐galactopyranose)‐b‐poly(4‐(4‐methoxyphenylazo)phenoxy methacrylate) [P(DMAEMA‐co‐MAGP)‐b‐PMAZO]. The composition, moleculer weight, and moleculer weight distribution of the resultant polymers were characterized by ¹H NMR and gel permeation chromatography. The micelles formed in aqueous solutions were simulated by various chemical and physical stimuli and characterized by dynamic light scattering, transmission electron microscopy, and UV‐vis spectroscopy. It was found that the glycopolymer is responsive to three different types of stimulus (light, temperature, and pH). The poly(2‐(dimethylamino) ethyl methacrylate) segments give thermo‐ and pH‐responsiveness. The presence of the azobenzene moiety endows the block copolymer to exhibit light‐responsiveness due to its reversible trans‐cis isomerization conversion. The triple stimuli‐responsive glycopolymer micelles can simulate biomacromolecues in vivo/in vitro environment and can be expected to open up new applications in various fields. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2014 , 52, 2131–2138     

Direct synthesis of amphiphilic block copolymers from glycidyl methacrylate and poly(ethylene glycol) by cationic ring‐opening polymerization and supramolecular self‐assembly thereof

Amphiphilic block copolymers composed of a hydrophilic poly(ethylene glycol) (PEG) block and a hydrophobic poly(glycidyl methacrylate) (PGMA) block were synthesized through cationic ring‐opening polymerization with PEG as the precursor. The model reactions indicated that the reactivity of the epoxy groups was higher than that of the double bonds in the bifunctional monomer glycidyl methacrylate (GMA) under the cationic polymerization conditions. Through the control of the reaction time in the synthesis of block copolymer PEG‐b‐PGMA, a linear GMA block was obtained through the ring‐opening polymerization of epoxy groups, whereas the double bond in GMA remained unreacted. The results showed that the molecular weight of the PEG precursor had little influence on the grafting of GMA, and the PGMA blocks almost kept the same length, despite the difference of the PEG blocks. In addition, the PGMA blocks only consisted of several GMA units. The obtained amphiphilic PEG‐b‐PGMA block copolymers could form polymeric core–shell micelles by direct molecular self‐assembly in water. The crosslinking of the PGMA core of the PEG‐b‐PGMA micelles, induced by ultraviolet radiation and heat instead of crosslinking agents, greatly increased the stability of the micelles. © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 43: 2038–2047, 2005     

Preparation of poly(styrene‐b‐N‐isopropylacrylamide) micelles surface‐linked with gold nanoparticles and thermo‐responsive ultraviolet–visible absorbance

Poly(styrene‐b‐N‐isopropylacrylamide) (PSt‐b‐PNIPAM) with dithiobenzoate terminal group was synthesized by reversible addition‐fragmentation‐transfer polymerization. The dithiobenzoate terminal group was converted into thiol terminal group with NaBH₄, resulting thiol‐terminated PSt‐b‐PNIPAM‐SH. After PSt‐b‐PNIPAM‐SH assembled into core‐shell micelles in aqueous solution, gold nanoparticles were in situ surface‐linked onto the micelles through the reduction of gold precursor anions with NaBH₄. Thus, temperature responsive core/shell micelles of PSt‐b‐PNIPAM surface‐linked with gold nanoparticles (PSt‐b‐PNIPAM‐Au micelles) were obtained. Transmission Electron Microscopy revealed the successful linkage of gold nanoparticles and the dependence of the number of gold nanoparticles per micelle on the molar ratio of HAuCl₄ to thiol group of PSt‐b‐PNIPAM. Dynamic Light Scattering analysis demonstrated thermo‐responsive behavior of PSt‐b‐PNIPAM‐Au micelles. Changing the temperature of PSt‐b‐PNIPAM‐Au micelles led to the shrinkage of PNIPAM shell and allowed to tune the distance between gold nanoparticles. Ultraviolet–visible (UV–vis) spectroscopy clearly showed the reversible modulation of UV–vis absorbance of PSt‐b‐PNIPAM‐Au micelles upon heating and cooling. © 2007 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 45: 5156–5163, 2007     

Micelle formation and sol–gel transition behavior of comb‐like amphiphilic poly((PLGA‐b‐PEG)MA) copolymers

Comb‐like amphiphilic poly(poly((lactic acid‐co‐glycolic acid)‐block‐poly(ethylene glycol)) methacrylate (poly((PLGA‐b‐PEG)MA)) copolymers were synthesized by radical polymerization. (PLGA‐b‐PEG)MA macromonomer was prepared by ring‐opening bulk polymerization of DL ‐lactide and glycolide using purified poly(ethylene glycol) monomethacrylate (PEGMA) as an initiator. (PLGA‐b‐PEG)MA macromonomer was copolymerized with PEGMA and/or acrylic acid (AA) by radical polymerization to produce comb‐like amphiphilic block copolymers. The molecular weight and chemical structure were investigated by GPC and ¹H NMR. Poly((PLGA‐b‐PEG)MA) copolymer aqueous solutions showed gel–sol transition behavior with increasing temperature, and gel‐to‐sol transition temperature decreased as the compositions of the hydrophilic PEGMA and AA increased. The gel‐to‐sol transition temperature of the terpolymers of the poly((PLGA‐b‐PEG)MA‐co‐PEGMA‐co‐AA) also decreased when the pH was increased. The effective micelle diameter obtained from dynamic light scattering increased with increasing temperature and with increasing pH. The critical micelle concentration increased as the composition of the hydrophilic monomer component, PEGMA and AA, were increased. The spherical shape of the hyperbranched polymers in aqueous environment was observed by atomic force microscopy. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 1954–1963, 2008     

Synthesis of PEG‐PNIPAM‐PLys hetero‐arm star polymer and its variation of thermo‐responsibility after the formation of polyelectrolyte complex micelles with PAA

A hetero‐arm star polymer, poly(ethylene glycol)‐poly(N‐isopropylacrylamide)‐poly(L‐lysine) (PEG‐PNIPAM‐PLys), was synthesized by “clicking” the azide group at the junction of PEG‐b‐PNIPAM diblock copolymer with the alkyne end‐group of poly(L‐lysine) (PLys) homopolymer via 1,3‐dipolar cycloaddition. The resultant polymer was characterized by gel permeation chromatography, proton nuclear magnetic resonance, and Fourier transform infrared spectroscopes. Surprisingly, the PNIPAM arm of this hetero‐arm star polymer nearly lose its thermal responsibility. It is found that stable polyelectrolyte complex micelles are formed when mixing the synthesized polymer with poly(acrylic acid) (PAA) in water. The resultant polyelectrolyte complex micelles are core‐shell spheres with the ion‐bonded PLys/PAA chains as core and the PEG and PNIPAM chains as shell. The PNIPAM shell is, as expected, thermally responsive. However, its lower critical solution temperature is shifted to 37.5 °C, presumably because of the existence of hydrophilic components in the micelles. Such star‐like PEG‐PNIPAM‐PLys polymer with different functional arms as well as its complexation with anionic polymers provides an excellent and well‐defined model for the design of nonviral vectors to deliver DNA, RNA, and anionic molecular medicines. © 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 47: 1450–1462, 2009     

Synthesis of Novel Thermo‐ and pH‐Responsive Poly(L‐lysine)‐Based Copolymer and its Micellization in Water

A series of novel temperature and pH responsive block copolymers composed of poly(N‐isopropylacrylamide) (PNIPAM) and poly(L ‐lysine) (PLL) were synthesized. The effect of pH and the length of PLL on the lower critical solution temperature (LCST) of PNIPAM, and the self‐assembly of these PLL‐based copolymers induced by temperature and pH changes were investigated by the cloud point method, dynamic light scattering (DLS) and environmental scanning electron microscopy (ESEM). These PNIPAM‐b‐PLL copolymers can self‐assemble into micelle‐like aggregates with PNIPAM as the hydrophobic block at acidic pH and high temperatures; and at alkaline pH and low temperatures, they can self‐assemble into particles with PLL as the hydrophobic block. The copolymers may have potential applications in biotechnological and biomedical areas as drug release carriers.

     

Novel temperature‐ and pH‐responsive graft copolymers composed of poly(L‐glutamic acid) and poly(N‐isopropylacrylamide)

A series of novel temperature‐ and pH‐responsive graft copolymers, poly(L ‐glutamic acid)‐g‐poly(N‐isopropylacrylamide), were synthesized by coupling amino‐semitelechelic poly(N‐isopropylacrylamide) with N‐hydroxysuccinimide‐activated poly(L ‐glutamic acid). The graft copolymers and their precursors were characterized, by ESI‐FTICR Mass Spectrum, intrinsic viscosity measurements and proton nuclear magnetic resonance (¹H NMR). The phase‐transition and aggregation behaviors of the graft copolymers in aqueous solutions were investigated by the turbidity measurements and dynamic laser scattering. The solution behavior of the copolymers showed dependence on both temperature and pH. The cloud point (CP) of the copolymer solution at pH 5.0–7.4 was slightly higher than that of the solution of the PNIPAM homopolymer because of the hydrophilic nature of the poly(glutamic acid) (PGA) backbone. The CP markedly decreased when the pH was lowered from 5 to 4.2, caused by the decrease in hydrophilicity of the PGA backbone. At a temperature above the lower critical solution temperature of the PNIPAM chain, the copolymers formed amphiphilic core‐shell aggregates at pH 4.5–7.4 and the particle size was reduced with decreasing pH. In contrast, larger hydrophobic aggregates were formed at pH 4.2. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 4140–4150, 2008     

Design and proof of reversible micelle‐to‐vesicle multistimuli‐responsive morphological regulations

Multistimuli‐responsive precise morphological control over self‐assembled polymers is of great importance for applications in nanoscience as drug delivery system. A novel pH, photoresponsive, and cyclodextrin‐responsive block copolymer were developed to investigate the reversible morphological transition from micelles to vesicles. The azobenzene‐containing block copolymer poly(ethylene oxide)‐b‐poly(2‐(diethylamino)ethyl methacrylate‐co‐6‐(4‐phenylazo phenoxy)hexyl methacrylate) [PEO‐b‐P(DEAEMA‐co‐PPHMA)] was synthesized by atom transfer radical polymerization. This system can self‐assemble into vesicles in aqueous solution at pH 8. On adjusting the solution pH to 3, there was a transition from vesicles to micelles. The same behavior, that is, transition from vesicles to micelles was also realizable on addition of β‐cyclodextrin (β‐CD) to the PEO‐b‐P(DEAEMA‐co‐PPHMA) solution at pH 8. Furthermore, after β‐CD was added, alternating irradiation of the solution with UV and visible light can also induce the reversible micelle‐to‐vesicle transition because of the photoinduced trans‐to‐cis isomerization of azobenzene units. The multistimuli‐responsive precise morphological changes were studied by laser light scattering, transmission electron microscopy, and UV–vis spectra. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011     

Effects of graft length and density of well‐defined graft polymers on the thermoresponsive behavior and self‐assembly morphology

A series of well‐defined thermoresponsive graft polymers with different lengths and graft densities, poly(glycidyl methacrylate)‐graft‐poly(N‐isopropylacrylate) (PGMA‐g‐PNIPAM), were successfully prepared by combination of controlled/living free radical polymerization and click chemistry. Effects of grafting length and density on the thermoresponsive behavior, aggregating mean diameter, and self‐assembly morphology are systematically investigated. The thermosensitive characteristics of graft polymers in aqueous solution prove that the length and graft density had positive co‐relationship with the lower critical solution temperature value and mean diameter of micelles as well as the size distribution, while the effect of graft length of polymers is more significant than that of density. Transmission electron microscopy analysis shows that the conformations of PGMA₄₅‐g‐PNIPAM₂₀ and PGMA₄₅‐g‐PNIPAM₄₆ with longer length and bigger grafting density in aqueous solutions are spherical nanoparticles with the increasing trend of the diameters, while that of PGMA₄₅‐g‐PNIPAM_{(73, 50%)} shows a spherical‐like morphology, which indicates that the graft length and density have a significant effect on the mean diameter of micelle but not on the self‐assembly morphology. These results reveal that to obtain desired thermoresponsive behavior and self‐assembly morphology of functional polymers, it is essential to design and fabricate the structure of graft polymers with proper length and graft density. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2014 , 52, 2442–2453     

Thin films of PS/PS‐b‐pnipam and ps/pnipam polymer blends with tunable wettability

We developed thin films of blends of polystyrene (PS) with the thermoresponsive polymer poly(N‐isopropylacrylamide) (PNIPAM) (PS/PNIPAM) and its diblock copolymer polystyrene‐b‐poly(N‐isopropylacrylamide) (PS/PS‐b‐PNIPAM) in different blend ratios, and we study their surface morphology and thermoresponsive wetting behavior. The blends of PS/PNIPAM and PS/PS‐b‐PNIPAM are spin‐casted on flat silicon surfaces with various drying conditions. The surface morphology of the films depends on the blend ratio and the drying conditions. The PS/PS‐b‐PNIPAM films do not show an increase in their water contact angles with temperature, as it is expected by the presence of the PNIPAM block. All PS/PNIPAM films show an increase in the water contact angle above the lower critical solution temperature of PNIPAM, which depends on the ratio of PNIPAM in the blend and is insensitive to the drying conditions of the films. The difference between the wetting behavior of PS/PS‐b‐PNIPAM and PS/PNIPAM films is due to the arrangement of the PNIPAM chains in the film. © 2019 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2019 , 57, 670–679     

Dual‐responsive supramolecular inclusion complexes of block copolymer poly(ethylene glycol)‐block‐poly[(2‐dimethylamino)ethyl methacrylate] with α‐cyclodextrin

A new class of temperature and pH dual‐responsive and injectable supramolecular hydrogel was developed, which was formed from block copolymer poly(ethylene glycol)‐block‐poly[(2‐dimethylamino)ethyl methacrylate] (PEG‐b‐PDMAEMA) and α‐cyclodextrin (α‐CD) inclusion complexes (ICs). The PEG‐b‐PDMAEMA diblock copolymers with different ratio of ethylene glycol (EG) to (2‐dimethylamino)ethyl methacrylate (DMAEMA) (102:46 and 102:96, respectively) were prepared by atom transfer radical polymerization (ATRP). ¹H NMR measurement indicated that the ratio of EG unit to α‐CD in the resulted ICs was higher than 2:1. Thermal analysis showed that thermal stability of ICs was improved. The rheology studies showed that the hydrogels were temperature and pH sensitive. Moreover, the hydrogels were thixotropic and reversible. The self‐assembly morphologies of the ICs in different pH and ionic strength environment were studied by transmission electron microscopy. The formed biocompatible micelles have potential applications as biomedical and stimulus‐responsive material. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 2143–2153, 2010     

Thermal and pH‐sensitive gold nanoparticles from H‐shaped block copolymers of (PNIPAM/PDMAEMA)‐b‐PEG‐b‐(PNIPAM/PDMAEMA)

Well‐defined H‐shaped pentablock copolymers composed of poly(N‐isopropylacrylamide) (PNIPAM), poly(N,N‐dimethylaminoethylacrylamide) (PDMAEMA), and poly(ethylene glycol) (PEG) with the chain architecture of (A/B)‐b‐C‐b‐(A/B) were synthesized by the combination of single‐electron‐transfer living radical polymerization, atom‐transfer radical polymerization, and click chemistry. Single‐electron‐transfer living radical polymerization of NIPAM using α,ω azide‐capped PEG macroinitiator resulted in PNIPAM‐b‐PEG‐b‐PNIPAM with azide groups at the block joints. Atom‐transfer radical polymerization of DMAEMA initiated by propargyl 2‐chloropropionate gave out α‐capped alkyne‐PDMAEMA. The H‐shaped copolymers were finally obtained by the click reaction between PNIPAM‐b‐PEG‐b‐PNIPAM and alkyne‐PDMAEMA. These copolymers were used to prepare stable colloidal gold nanoparticles (GNPs) in aqueous solution without any external reducing agent. The formation of GNPs was affected by the length of PDMAEMA block, the feed ratio of the copolymer to HAuCl₄, and the pH value. The surface plasmon absorbance of these obtained GNPs also exhibited pH and thermal dependence because of the existence of PNIAPM and PDAMEMA blocks. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2010     

Synthesis and micellization of PSt‐PNIPAM‐PDMAEMA hetero‐arm star polymer with double thermo‐responsibility

A hetero‐arm star polymer, polystyrene‐poly(N‐isopropylacrylamide)‐ poly(2‐(dimethylamino)ethylmethacrylate) (PSt‐PNIPAM‐PDMAEMA), was synthesized by “clicking” the alkyne group at the junction of PSt‐b‐PNIPAM diblock copolymer onto the azide end‐group of PDMAEMA homopolymer via 1,3‐dipolar cycloaddition. The resultant polymer was characterized by gel permeation chromatography, proton nuclear magnetic resonance spectroscopy and Fourier transform infrared spectroscopy. PSt‐PNIPAM‐PDMAEMA micelles with PSt block as core and PNIPAM and PDMAEMA blocks as shell were formed when adding the copolymer solution in THF into 10 folds of water. Lower critical solution temperature (LCST) of PNIPAM and PDMAEMA homopolymer is 32 °C for PNIPAM and 40 to 50 °C for PDMAEMA, respectively. Upon continuous heating through their LCSTs, PSt‐PNIPAM‐PDMAEMA core‐shell micelles exhibited two‐stage thermally induced collapse. The first‐stage collapse, from 20 to 34 °C, is ascribed to the shrinkage of PNIPAM chains; and the second‐stage collapse, from 38 to 50 °C, is due to the shrinkage of PDMAEMA chains. Dynamic light scattering was used to confirm the double phase transitions. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 47: 786–796, 2009     

Temperature‐Responsive Mixed‐Shell Polymeric Micelles for the Refolding of Thermally Denatured Proteins

We have fabricated a mixed‐shell polymeric micelle (MSPM) that closely mimics the natural molecular chaperone GroEL? GroES complex in terms of structure and functionality. This MSPM, which possesses a shared PLA core and a homogeneously mixed PEG and PNIAPM shell, is constructed through the co‐assembly of block copolymers poly(lactide‐b‐poly(ethylene oxide) (PLA‐b‐PEG) and poly(lactide)‐b‐poly(N‐isopropylacryamide) (PLA‐b‐PNIPAM). Above the lower critical solution temperature (LCST) of PNIPAM, the MSPM evolves into a core–shell–corona micelle (CSCM), as a functional state with hydrophobic PNIPAM domains on its surface. Light scattering (LS), TEM, and fluorescence and circular dichroism (CD) spectroscopy were performed to investigate the working mechanism of the chaperone‐like behavior of this system. Unfolded protein intermediates are captured by the hydrophobic PNIPAM domains of the CSCM, which prevent harmful protein aggregation. During cooling, PNIPAM reverts into its hydrophilic state, thereby inducing the release of the bound unfolded proteins. The refolding process of the released proteins is spontaneously accomplished by the presence of PEG in the mixed shell. Carbonic anhydrase B (CAB) was chosen as a model to investigate the refolding efficiency of the released proteins. In the presence of MSPM, almost 93 % CAB activity was recovered during cooling after complete denaturation at 70 °C. Further results reveal that this MSPM also works with a wide spectrum of proteins with more‐complicated structures, including some multimeric proteins. Given the convenience and generality in preventing the thermal aggregation of proteins, this MSPM‐based chaperone might be useful for preventing the toxic aggregation of misfolded proteins in some diseases.