New Nanophase Separated Intelligent Amphiphilic Conetworks and Gels

Amphiphilic conetworks (APCN) are new materials composed of covalently bonded otherwise immiscible hydrophilic and hydrophobic polymer chains. The amphiphilic nature of these new crosslinked polymers is indicated by their swelling ability in both hydrophilic and hydrophobic solvents. Special synthetic techniques have been developed for the preparation of these new unique materials, such as poly(2-hydroxyethyl methacrylate)-l-polyisobutylene (PHEMA-l-PIB), poly(methacrylic acid)-l-polyisobutylene (PMAA-l-PIB) and poly(N,N-dimethylaminoethyl methacrylate)-l-polyisobutylene (PDMAEMA-l-PIB) (-l- stands for linked by). Due to their unique architecture, macrophase separation of the immiscible components is prevented by the chemical bonding in the conetworks. As a results, phase separation leads to nanodomains with usually 2-20 nm domain sizes as shown by AFM measurements. The nanophase separated morphology may also lead to smart temperature responsive gels with high mechanical stability, such as in the case of poly(N,N-dimethylaminoethyl methacrylate)-l-polyisobutylene APCNs as discovered during these studies. In another approach, poly(2-hydroxyethyl methacrylate)-l-polyisobutylene and poly(methacrylic acid)-l-polyisobutylene APCNs were prepared by a special two-step process. The new PMAA-l-PIB polyelectrolyte APCNs possess smart (intelligent) reversible pH-responsive properties in aqueous media. These unique conetwork structures and properties of these new emerging materials may lead to numerous new potential applications, such as smart materialk products, sustained drug release matrices, biomaterials, nanohybrids, nanotemplates etc.     

Synthesis of well‐defined star‐shaped poly(ε‐caprolactone)/poly(ethylbene glycol) amphiphilic conetworks by combination of ring opening polymerization and “click” chemistry

Well‐defined star‐shaped hydrophobic poly(ε‐caprolactone) (PCL) and hydrophilic poly(ethylene glycol) (PEG) amphiphilic conetworks (APCNs) have been synthesized via the combination of ring opening polymerization (ROP) and click chemistry. Alkyne‐terminated six arm star‐shaped PCL (6‐s‐PCLx‐C?CH) and azido‐terminated PEG (N₃‐PEG‐N₃) are characterized by ¹H NMR and FT‐IR. The swelling degree of the APCNs is determined both in water and organic solvent. This unique property of the conetworks is dependent on the nanophase separation of hydrophilic and hydrophobic phases. The morphology and thermal behaviors of the APCNs are investigated by SEM and DSC respectively. The biocompatibility is determined by water soluble tetrazolium salt reagents (WST‐1) assay, which shows the new polymer networks had good biocompatibility. Through in vitro release of paclitaxel (PTX) and doxorubicin (DOX), the APCNs is confirmed to be promising drug depot materials for sustained hydrophobic and hydrophilic drugs. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016 , 54, 407–417     

Ideal tetrafunctional amphiphilic PEG/PDMS conetworks by a dual‐purpose extender/crosslinker. I. Synthesis

The synthesis of a new type of amphiphilic conetwork (APCN) consisting of well‐defined hydrophilic poly(ethylene glycol) (PEG) and hydrophobic polydimethylsiloxane (PDMS) segments is described. The conetwork is ideal (the lengths of each PEG and PDMS chain segments, respectively, are identical) and tetrafunctional (exactly four chains emanate from each crosslink site). The synthesis of the conetworks was achieved by the use of a novel dual‐purpose extender/crosslinker Y (bis [(dimethylsilyl)oxy]‐[(etoxydimethylsilyl)oxy]phenylsilane, (SiPh(SiH)₂OEt)), in two steps: (1) Synthesis of a new linear random multiblock copolymer (MBC) (AY)_n(BY)_m, where A is the hydrophilic PEG and B is the hydrophobic segment, and (2) Crosslinking the multiblocks by catalytic condensation of the SiOEt groups in the Y units. The extender/crosslinker fulfills two totally different functions: First, it extends two incompatible hydrophilic and hydrophobic prepolymers (PEG and PDMS) to a random MBC, and, subsequently, it cross‐links the multiblocks to the target APCN. The synthesis and characterization of the extender/crosslinker is also presented. © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 43: 4953–4964, 2005     

Novel Anti‐Biofouling Soft Contact Lens: l‐Cysteine Conjugated Amphiphilic Conetworks via RAFT and Thiol–Ene Click Chemistry

A unique l ‐cysteine conjugated antifouling amphiphilic conetwork (APCN) is synthesized through end‐crosslinking of well‐defined triblock copolymers poly(allyl methacrylate)‐b‐poly(ethylene glycol)‐b‐poly(allyl methacrylate) via a combination of reversible addition‐fragmentation chain transfer (RAFT) polymerization and thiol–ene “click” chemistry. The synthesized poly(ethylene glycol) macro‐RAFT agent initiates the polymerization of allyl methacrylate in a controlled manner. The vinyl pendant groups of the precursor partially conjugate with l ‐cysteine and the rest fully crosslink with mercaptopropyl‐containing siloxane via thiol–ene click chemistry under UV irradiation into APCNs, which show distinguished properties, that is, excellent biocompatibility, more than 39.6% water content, 101 barrers oxygen permeability, optimized mechanical properties, and more than 93% visible light transmittance. What's more, the resultant APCNs exhibit eminent resistance to protein adsorption, where the bovine serum albumin and lysozyme adsorption are decreased to 12 and 21 µg cm⁻², respectively. The outstanding properties of APCNs depend on the RAFT controlled method, which precisely designs the hydrophilic/hydrophobic segments and eventually greatly improves the crosslinking efficiency and homogeneity. Meantime, the l ‐cysteine monolayer can effectively reduce the surface hydrophobicity and prevent protein adsorption, which exhibits the viability for antifouling surface over and under ophthalmic devices, suggesting a promising soft contact lens.

     

Thermoplastic amphiphilic conetworks

Our main objective was the design, synthesis, characterization, and testing of a novel class of materials, thermoplastic amphiphilic conetworks (TP‐APCNs). A further objective was the evaluation of TP‐APCNs as biomaterials, for example, as immunoisolatory membranes in a bioartificial pancreas, or as extended‐wear soft contact lenses. The synthesis of the first TP‐APCNs was accomplished by blending an amphiphilic graft polymer, poly(dimethyl acryl amide)‐g‐polydimethylsiloxane (PDMAAm‐g‐PDMS), with a commercial PDMS‐containing polyurethane (PU). The common PDMS segments coalesce and form a single phase, whereas the hard/crystalline segments of the PU physically crosslink the blend. The properties of TP‐APCNs can be controlled by the graft/PU ratio and segment molecular weights. TP‐APCNs with cocontinuous hydrophilic and hydrophobic phases were prepared as demonstrated by swelling in water and n‐heptane. Depending on the blend ratio and molecular weights, optically clear water‐swollen TP‐APCNs with 0.5–4 MPa tensile strength, 70–280% elongation, together with 2–11 × 10^?7 cm²/s glucose permeability, and 1.2–8 × 10^?8 cm²/s insulin permeability were prepared. TP‐APCNs are processible by casting and molding. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 47: 682–691, 2009     

Synthesis,characterization, and crosslinking of methacrylate‐telechelic PDMAAm‐b‐PDMS‐b‐PDMAAm copolymers

The synthesis and molecular characterization of a new amphiphilic conetwork (APCN) designed for silicone hydrogel use is described. The synthesis strategy, outlined in Scheme 1 , calls for the preparation, by the RAFT technique, of a new methacrylate‐telechelic amphiphilic pentablock, MA‐PHEA‐b‐PDMAAM‐b‐PDMS‐b‐PDMAAm‐b‐PHEA‐MA, and its crosslinking to the target APCN. The sketch shows the architecture of the APCN (dotted lines, PDMAAm; solid lines, PDMS; clusters, MA‐based crosslinking sites; see Fig. 3 ). All six synthesis steps proceed smoothly and efficiently, and the products are optically clear, colorless membranes exhibiting properties appropriate for ophthalmic use. © 2007 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 45: 4284–4290, 2007     

Novel amphiphilic triblocks fitted with photocrosslinkable termini,and their photocrosslinking to conetworks

Two new telechelic amphiphilic triblock copolymers, HE₃‐PEG‐b‐PDMS‐b‐PEG‐HE₃ and HE₃‐PEG‐b‐PDMS‐b‐PEG‐HE₃, i.e., sequence‐reversed triblocks of hydrophilic poly(ethylene glycol) (PEG) and hydrophobic polydimethylsiloxane (PDMS) segments fitted with photocrosslinkable tri[2‐(3,4‐cyclohexane oxide)ethyl‐dimethylsiloxy]silane (HE₃) termini, were synthesized, characterized, photocrosslinked to amphiphilic conetworks (APCNs), and the properties of the APCNs were analyzed. APCNs in which the crosslinking sites are located in the hydrophobic domains exhibited significantly better mechanical properties than those in which the crosslinks were in the hydrophilic domains. The stiff domains formed of the UV‐crosslinkable HE₃ chain‐end substituents provide not only crosslinking but reinforcement as well. The crosslinking/reinforcement efficiency was greatly enhanced by the addition of excess HE₃. Water‐swollen APCNs were optically clear and exhibited mechanical properties appropriate for biomedical application. © 2007 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 174–185, 2008     

Biocompatible amphiphilic conetwork based on crosslinked star copolymers: A potential drug carrier

A series of amphiphilic conetworks (APCNs) is synthesized through crosslinking of well‐defined tri‐arm star diblock copolymers via atom transfer radical polymerization. A new three‐arm initiator is synthesized to initiate the polymerization of 2‐hydroxyethyl methacrylate (HEMA) via “core‐first” method. The resulting star HEMA homopolymers with well‐defined molecular weight and narrow polydispersity are used as macroinitiator to incorporate allyl methacrylate to get the star diblock copolymers. Then, the precursors with allyl pendant groups are fully crosslinked with polyhydrosiloxanes through hydrosilylation. The so‐prepared APCNs exhibit unique properties of microphase separation of hydrophilic (HI) and hydrophobic (HO) phases with small channel size, a variable swelling capacity, excellent biocompatibility, and outstanding mechanical strength (2 ± 0.5 MPa). The properties of APCNs depend on the ratio of HI to HO, which can be regulated via precise synthesis of the star diblock copolymers. The APCNs show well‐controlled drug release to choline theophyllinate, suggesting a promising intelligent drug carrier for controlled release. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2015 , 53, 2537–2545     

Anionic amphiphilic end‐linked conetworks by the combination of quasiliving carbocationic and group transfer polymerizations

A series of amphiphilic end‐linked conetworks was synthesized by the combination of two “quasiliving” polymerization techniques, quasiliving carbocationic (QLCCP) and group transfer polymerizations (GTP). The hydrophobic monomer was polyisobutylene methacrylate synthesized by the QLCCP of isobutylene and subsequent terminal modification reactions. The hydrophilic monomer was methacrylic acid (MAA) introduced via the polymerization of 2‐tetrahydropyranyl methacrylate followed by acid hydrolysis after (co)network formation. The conetwork syntheses were performed by sequential monomer/crosslinker additions under GTP conditions. All the precursors and the extractables from the conetworks were characterized by gel permeation chromatography and ¹H NMR. The resulting polymer conetworks were investigated in terms of their degree of swelling (DS) in aqueous media and in tetrahydrofuran (THF) over the whole range of ionization of the MAA units and in n‐hexane for uncharged conetworks. The DSs in water increased with the degree of ionization (DI) of the MAA units and the hydrophilic content in the conetwork, whereas the DSs in THF increased with the reduction of the DI of the MAA units. The effective pK of the MAA units in the conetworks increased from 8.4 to 10.5 with decreasing MAA content. These findings can facilitate the design of similar unique conetworks with adjustable swelling behavior and composition‐dependent pK values. © 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 47: 4289–4301, 2009     

Superoxide Dismutase Biosensors for Superoxide Radical Analysis

ABSTRACT

Some basic work has been performed on the development and optimisation of superoxide dismutase (SOD) biosensors for superoxide radical analysis. Initially we studied the possibility of obtaining a SOD biosensor using the Clark electrode as indicating sensor. However, the best results were obtained using as indicator a classical amperometric electrode for H₂O₂. In both cases the superoxide radical was generated in situ using the xanthine/xanthine oxidase (XOD) enzyme system, while the SOD was immobilised in kappa-carrageenan gel. The first application was realised by studying the effects in vitro on the superoxide radical of some molecules commonly accepted as radical scavengers.     

Stabilization of O/W emulsion with hydrophilic/hydrophobic clay particles

In this study, a stabilizing behavior of clay in a 40/60 w/w oil-in-water (O/W) emulsion is investigated by macro- and microscopic morphological observations, rheology, and X-ray diffraction measurements. Hydrophilic and hydrophobic clays (Montmorillonites) are tested for stabilization of emulsion. When hydrophilic clay showing interfacial localization is added to the emulsion, emulsion is not stable to phase separation (creaming). With hydrophobic clay, the emulsion shows phase inversion to water-in-oil (W/O) emulsion due to the increase in oil viscosity which results in phase separation of sedimentation. On the other hand, with the mixture of hydrophilic and hydrophobic clays, the emulsion shows a synergistic macroscopic and microscopic stabilization due to the formation of composite structure at the interface by hydrophilic and hydrophobic clays.     

Synthesis and characterization of biodegradable multicomponent amphiphilic conetworks with tunable swelling through combination of ring‐opening polymerization and “click” chemistry method as a controlled release formulation for 2,4‐dichlorophenoxyacetic acid herbicide

Multicomponent (two, three, and four component) amphiphilic conetworks (APCNs) with tunable swelling behaviors were fabricated through the ring opening polymerization and click chemistry utilizing various combinations of azide and alkyne functionalized poly (ethylene glycol) (PEG) and poly (caprolactone) (PCL) precursors. Prepare azido‐terminated star‐shaped PCL, azido‐terminated PEG, alkyne‐terminated PEG, and propargylated pentaerythritol were characterized by hydrogen‐1 proton nuclear magnetic resonance (¹H NMR) and Fourier‐transform infrared (FT‐IR) spectroscopy. The morphology and thermal behavior of the APCNs were studied by scanning electron microscopy (SEM) and differential scanning calorimetry (DSC). The swelling behavior of APCNs could be manipulated through an establishment of a balance between hydrophilic segments, hydrophobic segments, and cross‐linking density. The 2,4‐dichlorophenoxyacetic acid (2,4‐D) herbicide was entrapped in APCNs as a model agrochemical to study the release profile from APCNs. The obtained results showed that the release of 2,4‐D could be controlled by the swelling degree of APCNs. Finally, the biodegradability rates of APCNs were investigated in agricultural soil. The results exhibited that the decrease in the swelling degree led to decreased degradation rate of APCNs. According to obtained results, these APCNs could be used as biomaterials for the controlled release of agrochemicals.     

Poly(ethylene glycol)‐based amphiphilic model conetworks: Synthesis by RAFT polymerization and characterization

Poly(ethylene glycol) (PEG)‐containing quasi‐model amphiphilic polymer conetworks (APCNs) were prepared by reversible addition fragmentation chain transfer (RAFT) polymerization using α,ω‐bis(2‐cyanoprop‐2‐yl dithiobenzoate)‐PEG as a bifunctional RAFT macrochain transfer agent (macro‐CTA) and stepwise additions of a hydrophobic monomer and a crosslinker (crosslinker: macro‐CTA = 10:1, reaction time 24 h). Three different types of monomers, methyl methacrylate (MMA), n‐butyl acrylate and styrene, were employed as the hydrophobic monomers, whereas ethylene glycol dimethacrylate, ethylene glycol diacrylate and 1,4‐divinylbenzene served as the respective crosslinkers. PEG homopolymer hydrophilic quasi‐model networks were also prepared by RAFT‐polymerizing the three crosslinkers directly onto the two active ends of the PEG‐based macro‐CTA. From the three ABA triblock copolymers prepared, the MMA‐containing one was obtained at the highest polymerization yields. The crosslinking yields of the three ABA triblock copolymers with the corresponding crosslinkers were higher than those of the PEG‐based macro‐CTA with the same crosslinkers. The degrees of swelling (DSs) of all conetworks were measured in water and in tetrahydrofuran (THF). The DSs of the APCNs in THF were higher than those in water, whereas the reverse was true for the DSs of the hydrophilic homopolymer networks. Finally, the aqueous DSs of the APCNs were lower than those of the corresponding hydrophilic homopolymer networks. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 7556–7565, 2008     

Convenient synthesis of thermo‐responsive PtBA‐g‐PPEGMEMA well‐defined amphiphilic graft copolymer without polymeric functional group transformation

A series of well‐defined amphiphilic graft copolymers bearing hydrophobic poly(tert‐butyl acrylate) backbone and hydrophilic poly[poly(ethylene glycol) methyl ether methacrylate)] (PPEGMEMA) side chains were synthesized by sequential reversible addition fragmentation chain transfer (RAFT) polymerization and single‐electron‐transfer living radical polymerization (SET‐LRP) without any polymeric functional group transformation. A new Br‐containing acrylate monomer, tert‐butyl 2‐((2‐bromoisobutanoyloxy)methyl)acrylate (tBBIBMA), was first prepared, which can be homopolymerized by RAFT to give a well‐defined PtBBIBMA homopolymer with a narrow molecular weight distribution (M_w/M_n = 1.15). This homopolymer with pendant Br initiation group in every repeating unit initiated SET‐LRP of PEGMEMA at 45 °C using CuBr/dHbpy as catalytic system to afford well‐defined PtBBIBMA‐g‐PPEGMEMA graft copolymers via the grafting‐from strategy. The self‐assembly behavior of the obtained graft copolymers in aqueous media was investigated by fluorescence spectroscopy and TEM. These copolymers were found to be stimuli‐responsive to both temperature and ions. Finally, poly(acrylic acid)‐g‐PPEGMEMA double hydrophilic graft copolymers were obtained by selective acidic hydrolysis of hydrophobic PtBA backbone while PPEGMEMA side chains kept inert. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011     

Partially Methylated β-Cyclodextrin Analysis: A Systematic Approach to Appropriate RP Column Selection

In order to establish guidelines to help the analyst in the choice of the most suitable octadecyl or octyl bonded phase for the LC analysis of a given partially methylated β-CD sample, analyses of four commercially available dimethyl-β-cyclodextrins (DM-β-CDs) have been carried out on nine octyl (C₈) or octadecyl (C₁₈) silica bonded or polymeric bonded phases which differ significantly in their hydrophilic and hydrophobic properties. Chromatograms show that the nature of the packing materials has considerable influence on the resolution of complex mixtures composed of closely related compounds such as partially methylated β-CDs. Among various kinds of C₈ and C₁₈ bonded phases, silica based and monomeric phases which present both reinforced hydrophobic and polar interactions showed the best performance. Whatever the complexity of the commercial DM-β-CD, the richest chromatographic fingerprints, which best depict the complexity of the mixture, are obtained with Nucleosil 50-5-C₈ column. For the simplest mixtures, Nucleosil 50-5-C₈ column with acetonitrile-water (34:66) as mobile phase is the most suitable chromatographic system and leads to the best resolution between heptakis (2,6-di-O-methyl)-β-CD and hexakis (2,6-di-O-methyl)-mono(2,3,6-tri-O-methyl)-β-CD (14 OCH₃ and 15 OCH₃). This chromatographic system might enable an LC-MS coupling for direct identification of the different components in the mixture as well as control of batch to batch variations.     

Cockle shell-derived nanoparticles for optical urea biosensor development based on reflectance transduction

An optical biosensor for urea based on urease enzyme immobilised on functionalised calcium carbonate nanoparticles (CaCO₃-NPs) was successfully developed in this study. CaCO₃-NPs were synthesised from discarded cockle shells via a simple and eco-friendly approach, followed by surface functionalisation with succinimide ester groups. The fabricated biosensor is comprised of two layers. The first (bottom layer) contained functionalised NPs covalently immobilised to urease, and the second (uppermost layer) was alginate hydrogel physically immobilised to the pH indicator phenolphthalein. The biosensor provided a colorimetric indication of increasing urea concentrations by changing from colourless to pink. Quantitative urea analysis was performed by measuring the reflectance intensity of the colour change at a wavelength of 633.16 nm. The determination of urea concentration using this biosensor yielded a linear response range of 30–1000 mM (R² = 0.9901) with a detection limit of 17.74 mM at pH 7.5. The relative standard deviation of reproducibility was 1.14%, with no signs of interference by major cations, such as K⁺, Na⁺, NH?⁺, and Mg²⁺. The fabricated biosensor showed no significant difference with the standard method for the determination of urea in urine samples.     

Multiscale dynamics of the cell envelope of Shewanella putrefaciens as a response to pH change

The bacterial surface properties of gram-negative Shewanella putrefaciens were characterized by microbial adhesion to hydrocarbons (MATH), adhesion to polystyrene dishes, and electrophoresis at different values of pH and ionic strength. The bacterial adhesion to these two apolar substrates shows significant variations according to pH and ionic strength. Such behavior could be partly explained by electrostatic repulsions between bacteria and the solid or liquid interface. However, a similar trend was also observed at rather high ionic strength where electrostatic interactions are supposed to be screened. The nanomechanical properties at pH 4 and 10 and at high ionic strength were investigated by using atomic force microscopy (AFM). The indentation curves revealed the presence of a polymeric external layer that swells and softens up with increasing pH. This suggests a concomitant increase of the water permeability and so did of the hydrophilicity of the bacterial surface. Such evolution of the bacterial envelope in response to changes in pH brings new insight to the pH dependence in the bacterial adhesion tests. It especially demonstrates the necessity to consider the hydrophobic/hydrophilic surface properties of bacteria as not univocal for the various experimental conditions investigated.     

Self-assembled polypeptide-block-poly(vinylpyrrolidone) as prospective drug-delivery systems

Poly(β-benzyl-l-aspartate)-block-poly(vinylpyrrolidone) diblock copolymers (PAsp(OBzl)-b-PVP) having both hydrophobic and hydrophilic segments of various lengths were synthesized by a combination of ATRP and ROP. These amphiphilic diblock copolymers formed polymeric micelles consisting of a hydrophobic PAsp(OBzl) core and a hydrophilic PVP shell in aqueous solution. The block copolymer was characterized using ¹H NMR and gel permeation chromatography (GPC) analysis. Due to its core–shell structure, this block polymer forms unimolecular micelles in aqueous solutions. The micelle properties of PAsp(OBzl)-b-PVP diblock copolymer were extensively studied by dynamic light scattering (DLS), fluorescence spectroscopy, and transmission electron microscopy (TEM). PAsp(OBzl)-b-PVP copolymers displayed the lowest CMC and demonstrated little cytotoxicity when exposed to SW-1990 pancreatic cancer cells. In order to assess its application in biomedical area, the anti-inflammation drug prednisone acetate was loaded as the model drug in the polymeric nanoparticles. In vitro release behavior of prednisone acetate was investigated, which showed a dramatic responsive fast/slow switching behavior according to the pH-responsive structural changes of a micelle core structure. All of theses features are quite feasible for utilizing it as a novel intelligent drug-delivery system.     

PAA-g-PVAc Amphiphilic Graft Copolymer Synthesized by Atom Transfer Radical Polymerization

A new amphiphilic graft copolymer containing hydrophilic poly(acrylic acid) backbone and hydrophobic poly(vinyl acetate) side chains was synthesized via sequential atom transfer radical polymerization (ATRP) followed by selective hydrolysis of poly(methoxymethyl acrylate) backbone. Grafting‐from strategy was employed to synthesize PMOMA‐g‐PVAc graft copolymer (M_w/M_n=1.64) via ATRP. The final PAA‐g‐PVAc amphiphilic graft copolymer was obtained by selective acidic hydrolysis of PMOMA backbone in acidic environment without affecting the side chains. The critical micelle concentrations (cmc) in aqueous media were determined by a fluorescence probe technique. The micelle morphologies were found to be spheres.     

Temperature- and pH-responsive unimolecular micelles with a hydrophobic hyperbranched core

The dendritic unimolecular polymeric micelles with a hydrophobic dendritic polyester (Boltorn H40) as the core and the grafted biocompatible poly(N, N-diethylacrylamide)-b-poly(2-(dimethylamino)ethyl methacrylate) (PDEAAM-b-PDMAEMA) as the shell were synthesized by successive reversible addition–fragmentation transfer (RAFT) polymerization of N, N-diethylacrylamide (DEAAM) and 2-(dimethylamino)ethyl methacrylate (DMAEMA) monomers. Laser light scattering studies indicated that the resulting unimolecular polymeric micelles H40–PDEAAM–PDMAEMA with double stimuli-responsive shells exhibited a reversible two-stage phase transition behavior. The effect of varying the block length of PDMAEMA on the thermosensitivity of unimolecular polymeric micelles was studied. With an increase in the outer corona length of PDMAEMA, the temperature range of phase transition for the inner shell PDEAAM would become broad. As pH decreased to 2, the high hydrophilic PDMAEMA blocks with high protonation were independent of temperature, and the size of unimolecular polymeric micelles increased due to the extended-chain conformation of outer layer. The internal core cavities of the unimolecular polymeric micelles exhibited a great potential of loading guest molecules according to the analysis of pyrene probe fluorescence spectra.