Doubly thermo-responsive brush-linear diblock copolymers and formation of core-shell-corona micelles

Doubly thermo-responsive brush-linear diblock copolymer of poly[poly(ethylene glycol) methyl ether vinylphenyl]-block-poly(N-isopropylacrylamide) (PmPEGV-b-PNIPAM) is prepared by RAFT polymerization. The obtained brush-linear diblock copolymer exhibits two lower critical solution temperatures (LCSTs) corresponding to the linear poly(N-isopropylacrylamide) (PNIPAM) block and the brush poly[poly(ethylene glycol) methyl ether vinylphenyl] (PmPEGV) block in water. This brush-linear diblock copolymer undergoes a two-step temperature sensitive micellization. At temperature above the first LCST, the brush-linear diblock copolymer self-assembles into core-corona micelles with the dehydrated PNIPAM block forming the core and the solvated brush PmPEGV block forming the corona. When temperature increases above the second LCST, the polystyrene backbone in the brush PmPEGV block collapses onto the dehydrated PNIPAM core to form core-shell-corona micelles, in which the dehydrated PNIPAM block forms the core, the collapsed polystyrene backbone in the brush PmPEGV block forms the shell and the solvated poly(ethylene glycol) side-chains forms the corona. The effect of the length of the PNIPAM block and the length of the poly(ethylene glycol) side-chains on the thermo-responsive micellization and the size of core-shell-corona micelles is investigated.     

A correlation for the estimation of critical micellization concentrations and temperatures of polyols in aqueous solutions

An empirical correlation is presented for the estimation of critical micellization concentrations (CMC) and critical micellization temperatures (CMT) for poly(ethylene oxide)-block-poly(propylene oxide)-block-poly(ethylene oxide) copolymers in aqueous solutions. The CMC and CMT are expressed as a function of the polyol molecular weight, composition, and temperature (for CMC determination) or concentration (in the case of CMT). The correlation was developed from experimental CMT data for a set of 12 polyols that covered a wide range of molecular weights (2900–14600) and poly(ethylene oxide) contents (30–80 wt%) and is based on a simple expression for the standard free energy of micellization. Such a correlation should be useful to practitioners of the field as it allows easy prediction of CMC and CMT for a wide range of polyols with a minimal number of input parameters.     

Phenylboronic acid as a sugar- and pH-responsive trigger to tune the multiple micellization of thermo-responsive block copolymer

Phenylboronic acid-containing thermo-responsive block copolymer, poly(ethylene oxide)-b-poly(methoxydi(ethylene glycol) methacrylate-co- aminophenylboronic acid ethyl methacrylate) (PEO-b-P(DEGMMA-co-PBAMA)), was employed to investigate the multiple micellization and dissociation transitions. The unique sugar- and pH-responsive properties of phenylboronic acid were interesting to provide two parallel approaches to tune the critical micellization temperature (CMT) and multiple micellization of thermo-responsive block copolymer. The block copolymers were molecularly soluble below 21 °C and underwent micellization above 21 °C at pH 8.7. After glucose was added at 24 °C, hydrophobic phenylboronic acid was changed to hydrophilic boronate-glucose complex and the CMT of the thermo-sensitive block was increased which caused the dissociation of micelles. In parallel, if the solution pH was increased from 8.7 to 11 at 25 °C, micelles were disrupted because of the formation of hydrophilic phenylboronate anion, which elevated the CMT of the thermo-sensitive block polymer. The introduction of phenylboronic acid groups into the thermo-responsive block copolymers provides a novel approach to tune the multiple micellization and dissociation transitions that might have great potentials in biomedical applications.     

Micro- or nanoseparated phases in thermoset blends of an epoxy resin and PEO-PPO-PEO triblock copolymer

Diaminodiphenylmethane (DDM) curing at several temperatures of a diglycidyl ether of bisphenol A (DGEBA) epoxy resin modified with a poly(ethylene oxide)-block-poly(propylene oxide)-block-poly(ethylene oxide) (PEO-PPO-PEO) block copolymer has been investigated in order to characterize the miscibility and morphological features. Two distinct phases are present for every blends studied except for DGEBA/DDM modified with 10 wt% PEO-PPO-PEO and cured at low temperature. Depending on the curing condition, phase separation takes place at micro or nanoscale due to competition among kinetic and thermodynamic factors. The mechanistic approach used for modeling the curing reactions shows that the formation of epoxy-hydroxyl complex and the auto catalytic process are slightly decreased whilst the noncatalytic process is favoured upon copolymer addition. Modifier addition delays curing process as the influence of both formation of epoxy-hydroxyl complex and catalytic process on reaction rate is higher than the influence of noncatalytic process. A thermodynamic model describing a thermoset/block copolymer considered as only one entity system is proposed. The LCST behaviour allows to elucidate nano or micro separated structures obtained at low and high curing temperatures, respectively.     

Synthesis of poly(ethylene glycol)-<Emphasis Type="Italic">b</Emphasis>-poly(mercapto ethylacrylamide) diblock copolymer via atom transfer radical polymerization

Atom transfer radical polymerization was used to synthesize a well-defined poly(ethylene glycol)-b-poly(mercapto ethylacrylamide) (PEG-b-PMEAAm) diblock copolymer. Poly(ethylene glycol)-b-poly[N-(acryloxysuccinimide)](PEG-b-PNAS) was synthesized at 80 °C using methoxy-poly(ethylene glycol)-2-bromo propanoate (PEG-Br) and CuBr/2,2′-bipyridine as a macroinitiator and catalyst, respectively. The monomer conversion was determined by ¹H nuclear magnetic resonance (NMR) spectroscopy. The resulting PEG-b-PNAS diblock copolymer was characterized by gel permeation chromatography, Fourier transform infrared (FT-IR), and ¹H NMR spectroscopy. Disulfide groups were introduced by a simple reaction through the N-acryloxysuccinimide (NAS) moieties of the PEG-b-PNAS diblock copolymer with cystamine dihydrochloride in the presence of triethylamine. FT-IR spectroscopy was used to confirm the introduction of disulfide moieties into the polymer repeating units. Subsequently, a thiol-functionalized block copolymer was prepared using DL-dithiothreitol (DTT) as the reducing agent and the reduction step was monitored by ¹H NMR spectroscopy. This thiol group was transformed easily to a disulfide bond using FeCl₃ as an oxidizing agent. The transformation into disulfide could be visualized easily as insoluble polymeric particles formed from a clear solution of PEG-b-PMEAAm after oxidation.     

The influence of hydrophobic substitution on self-association of poly(ethylene oxide)-b-poly(n-alkyl glycidyl carbamate)s-b-poly(ethylene oxide) triblock copolymers in aqueous media

A series of amphiphilic poly(ethylene oxide)-b-poly(n-alkyl glycidyl carbamate)s-b-poly(ethylene oxide) triblock copolymers were synthesized by reaction between poly(ethylene oxide)-b-polyglycidol-b-poly(ethylene oxide) precursor copolymer and four n-alkyl isocyanates: ethyl, propyl, butyl and pentyl. After dissolution in water at room temperature the copolymers spontaneously form micelles. The critical micellization concentrations were determined by UV-VIS spectroscopy. The dimensions of the micelles, the aggregation numbers, and in some cases the micellar shape were determined by dynamic and static light scattering in a relatively broad temperature range. Special attention has been paid to the influence of the number of the carbon atoms in the alkyl chains, and respectively, the relative hydrophobicity of the middle block upon the self-association process. Clouding transition was observed for all of the copolymers, the clouding point being dependent upon the length of the alkyl chain.     

Micellization and sol-gel transition of novel thermo- and pH-responsive ABC triblock copolymer synthesized by RAFT

A well-defined thermo- and pH-responsive ABC-type triblock copolymer monomethoxy poly(ethylene glycol)-b-poly(2-(2-methoxyethoxy) ethyl methacrylate-co-N-hydroxymethyl acrylamide)-b-poly(2-(diethylamino) ethyl methacrylate), mPEG-b-P(MEO₂MA-co-HMAM)-b-PDEAEMA, was synthesized by reversible addition-fragmentation chain transfer polymerization (RAFT). The ABC-type triblock copolymer was endowed thermo- and pH-responsive, corresponding to the thermosensitive properties of P(MEO₂MA-co-HMAM) and pH-responsive properties PDEAEMA segments, respectively. The thermo- and pH-responsive properties of copolymer aqueous solutions were studied by UV transmittance measurements, dynamic light scattering (DLS), transmission electron microscopy (TEM). The results showed that the N-hydroxymethyl acrylamide (HMAM) content in triblock copolymer affected the lower critical solution temperature (LCST) of the triblock copolymer aqueous solution. The copolymer self-assembled into core-shell micelles, with the thermoresponsive P(MEO₂MA-co-HMAM) block and the hydrophilic PEG block as the shell, the hydrophobic PDEAEMA block as the core, in alkaline solution at room temperature. While in acidic media, when the temperature above the lower critical solution temperature (LCST) of the triblock copolymer aqueous solution, the copolymer self-assembled into P(MEO₂MA-co-HMAM)-core micelles with mixed hydrophilic PEG and pH-responsive PDEAEMA coronas. Sol-gel transition temperature (T_sol-gel) for the triblock copolymer determined by vial inversion test further indicated that it is dependent on the concentration of the triblock copolymers and solution pH. Copolymer hydrogel loaded with bovine serum albumin (BSA) were used for the sustained release study. The results indicated that the hydrogel was a promising candidate for controlling protein drug delivery.     

Synthesis and characterization of poly(ethylene glycol)-b-poly (l-lactide)-b-poly(l-glutamic acid) triblock copolymer

A biodegradable amphiphilic triblock copolymer of poly(ethylene glycol)-b-poly(l-lactide)-b-poly(l-glutamic acid) (PEG-b-PLLA-b-PLGA) was obtained by catalytic hydrogenation of poly(ethylene glycol)-b-poly(l-lactide)-b-poly(γ-benzyl-l-glutamic acid) (PEG-b-PLLA-b-PBLGA) synthesized by the ring-opening polymerization (ROP) of N-carboxyanhydride of γ-benzyl-l-glutamate (BLG-NCA) with amino-terminated MPEG-b-PLLA-NH₂ as a macroinitiator. MPEG-b-PLLA-NH₂ converted from MPEG-b-PLLA-OH first reacted with tert-Butoxycarbonyl-l-phenylalanine (Phe-^NBOC) and dicyclohexylcarbodiimide (DCC) and then deprotected the tert-butoxycarbonyl group. MPEG-b-PLLA-OH was prepared by ROP of l-lactide with monomethoxy poly(ethylene glycol) in the presence of stannous octoate. The triblock copolymer and its diblock precursors were characterized by ¹H NMR, FTIR, GPC and DSA (drop shape analysis) measurements. The lengths of each block polymers could be tailored by molecular design and the ratios of feeding monomers. The triblock polymer PEG-b-PLLA-b-PLGA containing carboxyl groups showed obviously improved hydrophilic properties and could be a good potential candidate as a drug delivery carrier.     

Thermoresponsive core-shell-corona micelles of poly(ethyleneglycol)-b-poly(N-isopropylacrylamide)-b-polystyrene

Core-shell-corona micelles with a thermoresponsive shell self-assembled by triblock copolymer of poly(ethyleneglycol)-b-poly(N-isopropylacrylamide)-b-polystyrene (PEG₄₅-b-PNIPAM₁₆₈-b-PS₄₆) are studied by ¹H NMR, light scattering and atomic force microscopy. The thermoresponsive triblock copolymer, which has a relatively short hydrophobic PS block, can disperse in water at room temperature to form core-shell-corona micelles with the hydrophobic PS block as core, the thermoresponsive PNIPAM block as shell and the hydrophilic PEG block as corona. At temperature above lower critical solution temperature (LCST) of the PNIPAM block, the PNIPAM chains gradually collapse on the PS core to shrink the size and change the structure of the resultant core-shell-corona micelles with temperature increasing. It is found that there possibly exists an interface between the PNIPAM shell and PEG corona of the core-shell-corona micelles at temperature above LCST of the PNIPAM block.     

Thermodynamics of micellization of poly-styrene-block-poly(ethylene/propylene) copolymers in decane

Light scattering was used to establish the dependence of the critical micelle temperature, CMT, on concentration for solutions of three polystyrene-block-poly(ethylene/propylene) copolymers in decane. Electron microscopy studies of particles isolated from the solutions showed that the micelles had narrow size distributions and micellization could be treated thermodynamically as a closed association. The light scattering results were used to calculate the standard Gibbs energies of micellization, ΔG^φ, and the standard enthalpy, ΔH^φ, and entropy contributions, —TΔS^φ. The values of ΔH^φ were large and negative, and markedly dependent on the molecular weight of the polystyrene block. The values of ΔG^φ for the three samples were on the other hand very similar to each other. The standard entropy contributions were unfavourable to micelle formation.     

α‐cyclodextrin assisted self‐assembly of poly(ethylene glycol)‐block‐poly(N‐isopropylacrylamide) in aqueous media

Poly(ethylene glycol)‐block‐poly(N‐isopropylacrylamide) (PEG‐b‐PNIPAM) block copolymers were synthesized by atom transfer radical polymerization, and the α‐cyclodextrin (α‐CD) induced self‐assembly characteristics of the system were elucidated. Below the lower critical solution temperature (LCST) of PNIPAM, CD threaded onto the PEG segments and induced micellization to form rod‐shaped nanostructures comprising of a PEG/α‐CD condensed phase and a PNIPAM shell. Increasing the temperature of system above the LCST caused the PNIPAM segments to collapse, which resulted in the dethreading of the CD. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013     

Preparation and thermally induced adhesion properties of a poly(vinyl alcohol)-g-N-isopropylacrylamide copolymer membrane

In the work described here, poly(vinyl alcohol)-g-N-isopropylacrylamide was prepared via graft polymerisation of N-isopropylacrylamide (NIPAM) onto poly(vinyl alcohol) (PVA). The structure and components of the polymer were characterised by differential thermogravimetry (DTG), differential scanning calorimetry (DSC), ¹H nuclear magnetic resonance spectroscopy (¹H NMR) and fourier transform infrared spectroscopy (FT-IR) testing, respectively. The T-type peel adhesion strengths and water contact angles of the prepared graft copolymer membranes were determined at different temperatures. The results indicated that the membrane has an obvious change in adhesion and water contact angle around the lower critical solution temperature (LCST) of the thermosensitive PNIPAM, regardless of the composition of the copolymers. Based on the scanning electron microscope (SEM) and energy dispersive spectrometric (EDS) analysis of freeze-dried graft copolymer membranes swollen in water at various temperatures, a mechanism for the thermally induced adhesion properties of the graft copolymer was proposed.     

Thermoresponsive behavior of graft copolymers based on poly(N,N-dimethylacrylamide-co-diacetoneacrylamide) side chains

A thermoresponsive graft copolymer was synthesized through free radical copolymerization and a “graft onto” method in aqueous solution. The primary structure of the graft copolymer is constituted of a partially hydrolyzed polyacrylamide (HPAM) backbone and thermosensitive side chains [amino-terminated poly(N,N-dimethylacrylamide-co-diacetone acrylamide) or P(DMA-co-DAAM)] with molecular weight around 10⁵ g/mol. The ¹H-NMR spectra at various temperatures showed the temperature of thermoassociation (T_ass) in the copolymer. At the same time, the pyrene fluorescence measurements demonstrated the formation of hydrophobic microdomains of P(DMA-co-DAAM) above T_ass. The thermothickening behavior of the graft copolymers was studied by viscosity measurements, and the results suggested that in semidilute solutions, the T_ass and the magnitude of thermothickening could be regulated by varying the hydrolysis degree of the backbone, the composition of side chains, and the addition of NaCl. The oscillatory shear experiments demonstrated that the copolymer can present a remarkable elasticity increase as the temerature increased to T_ass. These thermoassociating copolymers with temperature-tunable properties can have potential applications as smart materials in enhanced oil recovery. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019 , 135, 47051.     

Polymeric micelles based on photocleavable linkers tethered with a model drug

An amphiphilic block copolymer with photocleavable nitrobenzyl moieties in the side chain of the hydrophobic block was successfully synthesized by a combination of atom transfer radical polymerization (ATRP) and the Cu(I)-catalyzed 1,3-dipolar cycloaddition of azide and alkynes. 2-(Trimethylsilyloxy)ethyl methacrylate (HEMATMS) was polymerized from a poly(ethylene oxide) (PEO) macroinitiator via ATRP, leading to a well-defined block copolymer of PEO₁₁₃-b-PHEMATMS₄₅ with low polydispersity index (PDI = 1.09). After the polymerization, trimethylsilyl (TMS) groups were deprotected and then functionalized in-situ with 3-azidopropionic chloride to yield PEO-b-[2-(1-azidobutyryloxy)ethyl methacrylate] (PEO-b-PAzHEMA). Alkyne-functionalized pyrene with a photocleavable 2-nitrobenzyl moiety was added to the PEO-b-PAzHEMA backbone via click chemistry to produce the desired block copolymer with high fidelity. The resulting block copolymer was self-assembled in water to yield spherical micelles with an average diameter of 60 nm. Upon UV irradiation, 2-nitrobenzyl moieties were selectively cleaved, leading to the release of a model drug, 1-pyrenebutyric acid. Coumarin 102, another model drug that was physically encapsulated in the core of micelles during micellization in water, was also released at the same time. The general strategy presented herein can potentially be utilized for the preparation of polymeric vehicles that are capable of delivering multiple therapeutics under controlled individual release kinetics.     

Organic/inorganic hybrid materials from polypeptide-based block copolymers

Novel organic/inorganic hybrid material was synthesized from poly(acrylazapropyl-trimethoxysilane)-b-poly(N_ε-trifluoroacetyl-l-lysine) (P(AAPTMS)-b-P(TLL)) block copolymer using the sol–gel process. The treatment with ammonia solution permitted the hydrolysis of both trifluoro acetyl and trimethoxysilyl groups of the hydride copolymer followed by the condensation of the silanol groups, leading to cross-linked copolymers. The resulting cross-linked hybrid material was characterized using FT-IR, ²⁹Si NMR, DSC, TGA, and environmental scanning electron microscopy. These techniques evidenced that a siloxane network was obtained. Amphiphilic polypeptide/inorganic hybrid copolymers were achieved and self-organized as particles in water.     

Control of the confined and unconfined crystallization in glassy-crystalline poly(vinylcyclohexane)-b-poly(ethylene)-b-poly-(vinylcyclohexane) triblock copolymer in solution

The influence of the solvent evaporation rate on the crystallization of the poly(vinylcyclohexane)-b-poly(ethylene)-b-poly(vinylcyclohexane) (PVCH-PE-PVCH) triblock copolymer with the high T_g of PVCH segment in chloroform was investigated. The competition between the crystallization of PE block and the vitrification of PVCH in the triblock copolymer was controlled through changing the solvent evaporation rate in the solution system at different temperatures (T_e). It was found that the melting temperature (T_m) of PVCH-PE-PVCH samples increased with increasing the T_e when the T_e was lower than the solvent boiling point (bp), depending on the crystalline temperatures. However, when T_e was just a little above the solvent bp, two melting peaks, which corresponding to the fusion of the confined and unconfined crystals, respectively, were observed on the DSC curves of the samples. As T_e increased to be higher temperature, only one lower melting peak, which corresponding to the fusion of the confined crystals, existed for each samples. It was also found that the crystallinity (X_c) of the samples decreased gradually when T_e was lower than the solvent bp, and then decreased suddenly when T_e was just a little above the solvent bp, finally reached a plateau (about 13.5%) at higher T_e. The changes in X_c of the samples depend on the evaporating time in the solution. The results should be related to the competition between the crystallization of PE block in solvent and the vitrification of PVCH block with the solvent evaporation. Furthermore, the competition was controlled through changing the solvent evaporation rate. The confined and unconfined crystallization of the samples could be freely adjusted.     

Thermosensitive poly(N-isopropylacrylamide)-b-poly(ε-caprolactone) nanoparticles for efficient drug delivery system

To investigate thermosensitive polymeric nanoparticle, amphiphilic block copolymers of poly(N-isopropylacrylamice)-b-poly(ε-caprolactone) (PNPCL) with different PCL block lengths were synthesized by hydroxy-terminated poly(N-isopropyoacrylamide) (PNiPAAm) initiated ring opening polymerization of ε-caprolactone. Owing to their amphiphilic characteristics, the block copolymers formed self-assembled polymeric nanoparticles in aqueous milieus with thermosensitive PNiPAAm shell compartment. The characterizations of the nanoparticles revealed that the PNPCL nanoparticles showed PCL block length dependent physicochemical characters such as particle sizes, critical aggregation concentrations, and core hydrophobicities. Moreover, the thermosensitive PNiPAAm shells conferred unique temperature responsive properties such as phase transitions with temperature elevation over its lower critical solution temperature (LCST). The temperature induced phase transition resulted in the formation of PNiPAAm hydrogel layer on the PNPCL nanoparticle surface. The drug release tests revealed that the formation of thermosensitive hydrogel layer resulted in the enhanced sustained drug release patterns by acting as an additional diffusion barriers. Therefore, the introduction of thermosensitive polymers on polymeric nanoparticles might be a potential approaches to modulate drug release behaviors.     

Thermosensitive polymeric micelles based on the triblock copolymer poly(d,l‐lactide)‐b‐poly(N‐isopropyl acrylamide)‐b‐poly(d,l‐lactide) for controllable drug delivery

A thermosensitive amphiphilic triblock copolymer, poly(d,l ‐lactide) (PLA)‐b‐poly(N‐isopropyl acrylamide) (PNIPAAM)‐b‐PLA, was synthesized by the ring‐opening polymerization of d,l ‐lactide; the reaction was initiated from a dihydroxy‐terminated poly(N‐isopropyl acrylamide) homopolymer (HO‐PNIPAAM‐OH) created by radical polymerization. The molecular structure, thermosensitive characteristics, and micellization behavior of the obtained triblock copolymer were characterized with Fourier transform infrared spectroscopy, ¹H‐NMR, gel permeation chromatography, dynamic light scattering, and transmission electron microscopy. The obtained results indicate that the composition of PLA‐b‐PNIPAAM‐b‐PLA was in good agreement with what was preconceived. This copolymer could self‐assemble into spherical core–shell micelles (ca. 75–80 nm) in aqueous solution and exhibited a phase‐transition temperature around 26 °C. Furthermore, the drug‐delivery properties of the PLA‐b‐PNIPAAM‐b‐PLA micelles were investigated. The drug‐release test indicated that the synthesized PLA‐b‐PNIPAAM‐b‐PLA micelles could be used as nanocarriers of the anticancer drug adriamycin (ADR) to effectively control the release of the drug. The drug‐delivery properties of PLA‐b‐PNIPAAM‐b‐PLA showed obvious thermosensitive characteristics, and the release time of ADR could be extended to 50 h. This represents a significant improvement from previous PNIPAAM‐based drug‐delivery systems. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017 , 134, 45304.     

The Synergism Effect Between Sodium Dodecylbenzene Sulfonate and a Block Copolymer in Aqueous Solution

The synergistic behavior of sodium dodecylbenzene sulfonate (SDBS) with poly(ethylene oxide)–poly(propylene oxide)–poly(ethylene oxide) (PEO–PPO–PEO) block copolymer was studied using surface tension measurements. The surface tension of single and mixed solutions of SDBS and the block copolymer in this study was measured at different concentrations and at 25 °C. The critical micelle concentration (CMC) of these solutions was determined from the surface tension measurements. The SDBS gives higher CMC values than those of the block copolymer. The results show that the CMC value of SDBS decreases as the molar ratio of SDBS increases in the mixture solution with the block copolymer. The surface parameters of adsorption and micellization for single and mixed solutions were investigated. The results show that the surface and micellization properties of SDBS were improved as a result of mixing with the block copolymer. The mole fractions in the micelles and interaction parameters of the mixed solutions were calculated. The foam stability of single and mixed solutions at 25 °C was determined. The results show that the SDBS has more foam stability than the block copolymer and the foam stability increases as the molar ratio of SDBS increase in mixed solution of it with block copolymer.

Preparation of block-brush PEG-b-P(NIPAM-g-DMAEMA) and its dual stimulus-response

Well-defined dually responsive block-brush copolymer of poly(ethylene glycol)-b-[poly(N-isopropylacrylamide)-g-poly(N,N-dimethylamino-ethylmethacrylate)], [PEG-b-P(NIPAM-g-PDMAEMA)] was successfully prepared by the combination of atom transfer radical polymerization (ATRP) and click chemistry based on azide-capped PDMAEMA and alkyne-pending PEG-b-PNIPAM copolymer. Azide-capped PDMAEMA was synthesized through ATRP of DMAEMA monomer using an azide-functionalized initiator of β-azidoethyl-2-bromoisobutyrate. Alkyne-pending PEG-b-PNIPAM copolymer was obtained through ATRP copolymerization of NIPAM with propargyl acrylate. The final block-brush copolymer was synthesized by the click reaction between these two polymer precursors. Because of characteristics of three different blocks, the copolymer exhibited dually thermo- and pH-responsive behavior. The responsive behaviors of block-brush copolymer were studied by laser light scattering, temperature-dependent turbidity measurement and micro differential scanning calorimetry. The phase transition temperature of block-brush copolymer increased with the decrease of pH value. At pH = 5.0, the copolymer displayed weak thermo-responsive behavior and might form uni-molecular micelles upon heating. At higher pH values, the block-brush copolymer aggregated intermolecularly into the micelles during the phase transition.