Self-assembly of poly(ethylene glycol)-block-polypyridine copolymer into micelles and at silica surface: effect of molecular architecture on silica dispersion

We have newly synthesized amphiphilic block copolymers composed of hydrophilic poly(ethylene glycol) (PEG) and hydrophobic pyridine segments (PEG-b-Py). Chain transfer agent-terminated PEG was subsequently chain-extended with 3-(4-pyridyl)-propyl acrylate to obtain PEG-b-Py by reversible additional-fragmentation chain transfer polymerization. Particularly, the effect of varying molecular weight (Mn) of PEG (Mn?=?2,000 and 5,000) and Py in the block copolymers was investigated in terms of critical micelle concentration, pyrene solubilization, micelle size distribution, and association number per micelle. Based on the amphiphilic balance, PEG-b-Pys formed core-shell type polymer micelle. The association number of PEG2k-b-Py was higher than that of PEG5k-b-Py, suggesting the degree of phase separation strongly depended on PEG Mn. Furthermore, the adsorption of PEG-b-Py copolymer onto silica nanoparticles as dispersant was studied to estimate the effect of PEG Mn in the copolymers and their solubility in the medium on the adsorption. Adsorbed density of PEG2k-b-Py copolymer onto silica nanoparticle was higher than that of PEG5k-b-Py, which was significantly correlated with the degree of phase separation. Furthermore, the adsorbed amount of copolymer increased with the increase in ionic strength due to the reduced solubility of PEG in the buffer solution. The resultant dispersion stability was highly correlated with the graft density of copolymer onto silica surface. However, the stability of PEG2k-b-Py coated particles was lower than that with PEG5k-b-Py, this is attributed to the relatively thin layer of PEG at the silica surface, which cannot provide the system with sufficient steric stabilization as the salt concentration increases. These fundamental investigations for the surface modification of the nanoparticle provide the insight into the highly stable colloidal dispersion, particularly in the physiological condition with high ionic strength.     

Affinity capillary electrophoretic DNA separation using PEG-oligodeoxyribonucleotide block copolymers: relationship between peak resolution and affinity strength

Capillary electrophoretic separation of chemically synthesized ssDNA and a single-base-substituted one (normal and mutant ssDNA, respectively) was demonstrated using a PEG-oligodeoxyribonucleotide block copolymer (PEG-b-ODN) as an affinity ligand. When the base sequence of PEG-b-ODN was designed to be complementary to part of normal ssDNA including the base-substituted site, the electrophoretic mobility of normal ssDNA significantly decreased whereas that of mutant ssDNA slightly changed. Resolution of the separation strongly depended on the ODN length of the copolymer, the capillary temperature, and the Mg2+ concentration in the running buffer, indicating that the retardation of migration of normal ssDNA was induced by the reversible hybridization with PEG-b-ODN. It was found that the dissociation constant (K(d)) of the duplex between normal ssDNA and the affinity probe ODN should be smaller than 10(-6) M to achieve the good peak separation. In addition, we calculated the mobility of the complex (mu(C)) between normal ssDNA and PEG-b-ODN using a two-state model. The base sequence of affinity probe ODN appropriate to achieve the sufficient resolution will be predicted on the basis of the mu(C) and K(d )values.     

Quantitative SNP genotyping by affinity capillary electrophoresis using PEG-oligodeoxyribonucleotide block copolymers with electroosmotic flow

Quantitative SNP detection was demonstrated with an ACE using a PEG-oligodeoxyribonucleotide block copolymer (PEG-b-ODN) as a probe in the presence of an EOF. The probe's PEG segment with large molecular weight and small polydispersity yielded a high resolution in the separation of a chemically synthesized 60-base ssDNA (WT) and its single-base-substituted mutant (MT). A mixture of WT and MT was clearly separated within 10 min by simultaneously using two types of PEG-b-ODN probes whose ODN segments were complementary to WT and MT and whose PEG segments were of different lengths. The peak area ratio between WT and MT was in good agreement with the feed ratio. The averaged difference between the feed and observed ratio of MT was determined to be 0.23%, which is lower than that of any other methods. The ACE using the PEG-b-ODN probes in the presence of EOF could be utilized as a facile method for estimating SNP allele frequency in various research fields.     

Thiol-ene Reaction: An Efficient Tool to Design Lipophilic Polyphosphoesters for Drug Delivery Systems

Poly(ethylene glycol)-b-polyphosphoester (PEG-b-PPE) block copolymer nanoparticles are promising carriers for poorly water soluble drugs. To enhance the drug loading capacity and efficiency of such micelles, a strategy was investigated for increasing the lipophilicity of the PPE block of these PEG-b-PPE amphiphilic copolymers. A PEG-b-PPE copolymer bearing pendant vinyl groups along the PPE block was synthesized and then modified by thiol-ene click reaction with thiols bearing either a long linear alkyl chain (dodecyl) or a tocopherol moiety. Ketoconazole was used as model for hydrophobic drugs. Comparison of the drug loading with PEG-b-PPE bearing shorter pendant groups is reported evidencing the key role of the structure of the pendant group on the PPE backbone. Finally, a first evidence of the biocompatibility of these novel PEG-b-PPE copolymers was achieved by performing cytotoxicity tests. The PEG-b-PPE derived by tocopherol was evidenced as particularly promising as delivery system of poorly water-soluble drugs.     

Fabrication of biofunctional complex micelles with tunable structure for application in controlled drug release

In acidic solution, complex micelles were formed by diblock copolymers of poly (ethylene glycol)-b-poly (ε-caprolactone) (PEG-b-PCL) and folate-poly (2-(dimethylamino) ethyl methylacrylate)-b-poly (ε-caprolactone) (Fol-PDMAEMA-b-PCL) with a PCL core, a mixed PEG/Fol-PDMAEMA shell. The surface charge of the complex micelles was positive at acidic surroundings for the protonated PDMAEMA. With increasing pH value to 7.4 (above pK _a of PDMAEMA), these micelles could convert into a core-shell-corona (CSC) structure composing a hydrophobic PCL core, a collapsed PDMAEMA shell, and a soluble PEG corona. Compared to core-shell micelles formed by PEG-b-PCL, micelles with CSC structure can prolong degradation by enzyme. Doxorubicin was physically loaded into the PCL core. The drug release rate was pH-dependent. At pH 5.5, complex micelles with core-shell structure showed faster drug release rate, while at pH 7.4, complex micelles gained CSC structure which control the drug release at a lower rate. The multifunctional complex micelles were prepared for enhanced tumor therapy.     

Modular synthesis of a block copolymer with a cleavable linkage via “click” chemistry

A diblock copolymer poly(ethylene glycol)-block-polystyrene or PEG-b-PS with an olefinic double bond at the PEG and PS junction has been prepared by modular synthesis via “click” chemistry. This involved the synthesis of PS by atom transfer radical polymerization and the nucleophilic substitution of the terminal bromide group with azide to yield azide-terminated PS. PEG with an alkynyl terminal group was prepared from reacting carboxyl-end-functionalized PEG with 4-hydroxybut-2-enyl prop-2′-ynyl succinate, which contained an alkynyl group as well as an olefin group. The PS and PEG polymers were linked via the 1,3-dipolar cycloaddition of the end azide and alkyne groups. The obtained copolymer was characterized by ¹H NMR spectroscopy and size exclusion chromatography (SEC). SEC analysis indicated that the diblock copolymer produced could be readily cleaved by ozonolysis to regenerate the constituent homopolymers.     

Fabrication of polymeric micelles with core–shell–corona structure for applications in controlled drug release

Thermo-responsive polymeric micelles of poly (ethylene glycol)-b-poly(2-hydroxyethyl methacrylate-g-lactide)-b-poly(N-isopropylacrylamide) (PEG-P(HEMA-PLA)-PNIPAM) with core–shell–corona structure were fabricated for applications in controlled drug release. The graft copolymer of PEG-P(HEMA-PLA)-PNIPAM was self-assembled into core–shell micelles with a densely PLA core and mixed PEG/PNIPAM shells at 25 °C in aqueous media. By increasing the temperature above the lower critical solution temperature of PNIPAM, these core–shell micelles could be converted into core–shell–corona micelles because of the collapse of PNIPAM block on the PLA core as the inner shell and the soluble PEG block stretching outside as the outer corona. Anticancer drug doxorubicin (DOX) was loaded in the polymeric micelles as a model drug. Compared with polymeric micelles formed by liner PEG-b-PLA-b-PNIPAM triblock copolymer, these polymeric micelles exhibited higher loading capacity, and release of DOX from the polymeric micelles with core–shell–corona structure was well-controlled.     

pH-labile sheddable block copolymers by RAFT polymerization: Synthesis and potential use as siRNA conjugates

Well-defined amphiphilic block copolymers composed of hydrophilic and hydrophobic blocks linked through an acid-labile acetal bond were synthesized directly by RAFT polymerization using a new poly(ethylene glycol) (PEG) macroRAFT agent modified with an acid-labile group at its R-terminal. The new macroRAFT agent was used for polymerization of poly(t-butyl methacrylate) (PtBMA) or poly(cholesterol-methacrylate) (PCMA) to synthesize well-defined block copolymers with a PEG block sheddable under acidic conditions. The chain extension polymerization kinetics showed known traits of RAFT polymerization. The molecular weight distributions of the copolymers prepared using the new macroRAFT agent remained below 1.2 during the polymerizations and the molecular weight of the copolymers was linearly proportional to monomer conversions. The acid-catalyzed hydrolysis behavior of the PEG-macroRAFT agent and the PEG-b-PtBMA (Mn = 13,600 by GPC, PDI = 1.10) was studied by GPC, ¹H NMR and UV–vis spectroscopy. The half-life of acid-hydrolysis was 70 min at pH 2.2 and 92 h at pH 4.0. The potential use of the pH-labile shedding behavior of the copolymers was demonstrated by conjugating a thiol-modified siRNA to ω-pyridyldisulfide modified PEG-b-PCMA. The resultant PEG-b-PCMA-b-siRNA triblock modular polymer released PCMA-b-siRNA segment in acidic and siRNA segment in reductive conditions, as confirmed by polyacrylamide gel electrophoresis.     

Study on Self-assembly of Poly(ethylene glycol)- block-poly(γ-benzyl L -glutamate)-graft-poly(ethylene glycol) Copolymer and Poly(γ-benzyl L -glutamate)- block-poly(ethylene glycol) Copolymer in Ethanol

Poly(ethylene glycol)-block-poly(γ-benzyl L-glutamate)-graft-poly(ethylene glycol) (PEG-b-PBLG-g-PEG) copolymer was synthesized by the ester exchange reaction of poly(γ-benzyl L-glutamate)-block-poly(ethylene glycol) (PBLG-block-PEG) copolymer with PEG chain, and PBLG-block-PEG copolymer was prepared by a standard N-carboxyl-γ-benzyl-L-glutamate anhydride (NCA) method. Nuclear magnetic resonance (NMR) spectroscopy was used to confirm the components of PBLG-block-PEG and PEG-b-PBLG-g-PEG. The self-association behaviors of PBLG-block-PEG and PEG-b-PBLG-g-PEG in ethanol were investigated by transmission electron microscopy (TEM), dynamic laser scattering (DLS), and viscometry. The experimental results revealed that the different molecular structures could exert marked effects on the self-assembly behaviors of PBLG-block-PEG and PEG-b-PBLG-g-PEG in ethanol. PBLG-block-PEG and PEG-b-PBLG-g-PEG could self-assemble to form polymeric micelles with a core-shell structure in the shapes of plump spherical and regular rice-like, respectively. Effects of the introduction of PBLG homopolymer on the average particle diameter of the micelles of PBLG-block-PEG and PEG-b-PBLG-g-PEG and influence of testing temperature on the critical micelle concentration of different copolymers were studied.     

Preparation of intermediary layer crosslinked micelles from a photocrosslinkable amphiphilic ABC triblock copolymer

To prepare intermediary layer crosslinked micelles, a photocrosslinkable amphiphilic ABC triblock copolymer, poly(ethylene glycol)-b-poly(2-cinnamoyloxyethyl methacrylate)-b-poly(methyl methacrylate) (PEG-PCEMA-PMMA), was synthesized and its micellar characteristics were investigated. The triblock copolymer of PEG-b-poly(2-hydroxyethyl methacrylate)-b-PMMA (PEG-PHEMA-PMMA) (M_n = 9800 g/mol, M_w/M_n = 1.33) was first polymerized by activators generated by electron transfer (AGET) atom transfer radical polymerization (ATRP) using a PEG macroinitiator in a mixed solvent of anisole/2-isopropanol (3/1 v/v). The middle block of the copolymer was then functionalized with cinnamoyl chloride. The degrees of polymerization of the PEG, PHEMA, and PMMA blocks were 113, 18 and 21, respectively. The critical micelle concentration (CMC) of the PEG-PCEMA-PMMA was 0.011 mg/mL. The PEG-PCEMA-PMMA micelles were spherically shaped with an average diameter of 43 nm. The intermediary layer of the PEG-PCEMA-PMMA micelles was crosslinked by UV irradiation. Not all of the cinnamate groups underwent photocrosslinking probably due to a lack of other cinnamate groups in their immediate vicinity. However, the degree of photocrosslinking of the intermediary layer of the PEG-PCEMA-PMMA micelles was sufficient to give excellent colloidal stability, even in different external environments.     

Confined crystallization,melting behavior and morphology in PEG-b-PLA diblock copolymers: Amorphous versus crystalline PLA

In diblock copolymers, the constraining effects of different stereochemical structure of high-T_m block on crystallization and melting behaviors of other constituent are supposed to be different. In this work, PEG-b-PDLLA and PEG-b-PLLA were synthesized, and crystallization kinetics, crystalline structure, melting behaviors of PEG blocks and morphology development in these systems were evaluated. Compared to those connected to PLLA, PEG-b-PDLLA exhibited lower crystallization rates, implying that connectivity of amorphous chain exerted more pronounced effect on crystallization rate of PEG than that of steric hindrance of PLLA crystallites. While all PEG-b-PDLLA samples showed a single endothermic peak during heating process, multiple melting peaks were observed in PEG-b-PLLA associated with composition, crystallization temperature and cooling rate of PLLA. A lamellar structure was formed by the crystallization of PEG in all PEG-b-PDLLA, however, when PEG-b-PLLA crystallized at room temperature directly, unexpected results occurred: lamellar for diblock copolymers with 31.5 and 48.0 wt% PLA or cylindrical structure for the diblock copolymers with 56.1 and 63.8 wt% PLA. Depending on composition, PEG-b-PLLA created one or two types of lamellar stacks after sequential crystallization of PLLA and PEG. © 2020 Wiley Periodicals, Inc. J. Polym. Sci. 2020 , 58, 455–465     

Aggregation Behavior of Poly(ethylene glycol)-block-poly (γ-benzyl L-glutamate)-graft-poly(ethylene glycol) Copolymer and its Blends with Poly(γ-benzyl L-glutamate) Homopolymer in Mixed Solvents

Poly(ethylene glycol)-block-poly(γ-benzyl L-glutamate)-graft-poly(ethylene glycol) (PEG-b-PBLG-g-PEG) copolymer was synthesized by the ester exchange reaction of PBLG-block-PEG copolymer with mPEG. The self-association behaviors of PEG-b-PBLG-g-PEG and its blends with PBLG homopolymer in the mixtures of ethanol and dimethylformamide (DMF) were investigated by transmission electron microscopy (TEM), dynamic light scattering (DLS), and viscometry. Effects of the introduction of PBLG homopolymer, the grafting ratio, and the DMF content on the self-association behaviors of PEG-b-PBLG-g-PEG copolymer in the mixtures of ethanol and DMF were mainly researched. It was revealed that PEG-b-PBLG-g-PEG copolymer could self-assemble to form polymeric micelles with a core-shell structure in various shapes from different preparation conditions. The critical micelle concentration (CMC) and the average particle diameter of the micelles formed by PEG-b-PBLG-g-PEG copolymer in the mixed solvents also changed with different preparation conditions.     

Responsive polymer-based multicolor fluorescent probes for temperature and Zn2+ ions in aqueous media

We report on the fabrication of fluorescent and multicolor probes for Zn²⁺ ions and temperature from a mixture of three types of fluorophore-labeled responsive block copolymers in aqueous media. Quinoline-based Zn²⁺-recognizing fluorescent monomer ZQMA, red-emitting rhodamine B-based monomer RhBEA, and blue-emitting coumarin derivative Coum-OH, were synthesized first. A ZQMA-labeled well-defined double hydrophilic block copolymer (DHBC), PEG-b-P(MEO₂MA-co-ZQMA), was synthesized via reversible addition-fragmentation chain-transfer (RAFT) polymerization of 2-(2-methoxyethoxy)ethyl methacrylate (MEO₂MA) and ZQMA by utilizing a PEG-based macroRAFT agent. Following similar procedures, PEG-b-P(St-co-RhBEA) amphiphilic diblock copolymer and PEG-b-P(MEO₂MA-co-Coum) DHBC were also synthesized, where P(St-co-RhBEA) was a RhBEA-labeled polystyrene (PS) block. At room temperature in aqueous solution, almost nonfluorescent PEG-b-P(MEO₂MA-co-ZQMA) can effectively bind Zn²⁺ ions, leading to prominent green fluorescence enhancement due to the coordination of ZQMA with Zn²⁺ ions. However, by mixing red-emitting PEG-b-P(St-co-RhBEA) and blue-emitting PEG-b-P(MEO₂MA-co-Coum) with PEG-b-P(MEO₂MA-co-ZQMA) at an appropriate ratio, three color transitions could be observed. In the absence of Zn²⁺ ions, a mixed pink fluorescent originating from Coum and RhBEA was observed; upon the addition of a certain amount of Zn²⁺ ions, the green fluorescence enhanced dramatically, leading to a white fluorescence readout. By further increasing the amount of Zn²⁺ ions, the green fluorescence further enhanced and overwhelmed the blue and red emissions, leading to a green-dominant mixed-fluorescence emission. In addition, upon increasing the temperature, the fluorescence of Coum decreased considerably due to the fluorescence-resonance energy transfer (FRET) between Coum and ZQMA moieties. In this way, a ratiometric fluorescent thermometer can be constructed.     

Synthesis and self-assembly of poly(ethylene glycol)-block-poly(N-3-(methylthio)propyl glycine) and their oxidation-sensitive polymersomes

Amphiphilic block copolymers poly(ethylene glycol)-block-poly(N-3-(methylthio)propyl glycine) (PEG-b-PMeSPG) were synthesized via ring-opening polymerization of N-3-(methylthio)propyl glycine N-thiocarboxyanhydride (MeSPG-NTA) initiated by amino-terminated PEG. The self-assemblies of three PEG-b-PMeSPG copolymers with different PMeSPG block lengths were first prepared by nanoprecipitation method using THF and DMF, respectively, as the organic solvent, and their morphologies were studied by Cryo-EM and DLS. To prepare polymersomes loaded with glucose oxidase (GOx), double emulsion method followed by extrusion treatment was employed. The oxidation-responsive disruption of polymersomes was achieved upon the introduction of glucose because of the oxidants generated in-situ by GOx/glucose.     

pH-Responsive PEGylated nanogels as targetable and low invasive endosomolytic agents to induce the enhanced transfection efficiency of nonviral gene vectors

A pH-responsive PEGylated nanogel was successfully prepared by means of emulsion copolymerization of 2-(N,N-diethylamino)ethyl methacrylate (AMA) with heterobifunctional poly(ethylene glycol) (PEG) bearing a 4-vinylbenzyl group at the α-end and a lactose moiety at the ω-end in the presence of potassium persulfate and ethyleneglycol dimethacrylate as a cross-linker. Polyplex micelle composed of PEG-block-poly(l-lysine) copolymer and plasmid DNA (PEG-b-PLL/pDNA) exhibited a far more efficient transfection ability in the presence of lac-nanogel-8k-1.0% (PEG, M _n = 8000; cross-linking density, 1.0%) than the PEG-b-PLL/pDNA polyplex micelle alone (in the absence of lac-nanogel-8k-1.0%), suggesting that an appreciable fraction of lac-nanogel-8k-1.0% along with the PEG-b-PLL/pDNA polyplex micelle is taken up into the HuH-7 cells through the asialoglycoprotein receptor-mediated endocytosis process mediated by the cluster of a large number of lactose moieties on the surface of lac-nanogel-8k-1.0%, followed by the effective disruption of the endosome by the buffer effect of the unprotonated PAMA core in lac-nanogel-8k-1.0%. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Synthesis,Characterization and Aqueous Solution Behavior of a pH-responsive Double Hydrophilic Block Copolymer

The pH-responsive double hydrophilic block copolymer poly(ethylene glycol)-b-poly(methacylic acid-co-4-vinyl benzylamine hydrochloride salt) (PEG-b-PMAA/PVBAHS) was synthesized. A series of PEG-b-PMAA/PVBAHS with different molecule weights and compositions were characterized by IR, ¹H-NMR, elemental analysis and TGA. With different MAA/VBAHS ratio, the PEG-b-PMAA/PVBAHS copolymers had the different isoelectric point (IEP). Supermolecular structures of the block copolymers could be formed by the interionic interactions at different solution pH. Experiment results showed that the structures of the pH-responsive copolymers in aqueous solution could be changed at different pH environments. The aggregation of this double hydrophilic block copolymer in aqueous solution was determined by both of solution pH and copolymer composition.     

Epitaxial single crystal surface patterning and study of physical and chemical environmental effects on crystal growth

For designing the responsive polymer brushes, and tuning the local and chemical surface responses to the external stimuli, the epitaxial single crystals were patterned by combination of bared surfaces of poly(ethylene glycol) (PEG) substrate, polymer homo-brushes constructed from poly(ethylene glycol)-b-polystyrene (PEG-b-PS) as well as poly(ethylene glycol)-b-poly(methyl methacrylate) (PEG-b-PMMA), and PEG-b-PS/PEG-b-PMMA mixed-brush channels. To achieve this target, various single crystals and epitaxial structures grown from dilute solutions through self-seeding approach were utilized as seeds to fabricate the next channels. The characteristics and morphologies of different channels were detectable by atomic force microscopy (AFM). The influence of chemical (solvent quality and interaction of substrate with different brushes) and physical (presence of brushes from another type in their vicinity) environments on crystallization was studied. Due to the effect of chemical environment, the PS brushes hampered the growth of PEG crystals at M _n ^PS?=?10,000 g/mol. However, the PMMA brushes allowed PEG crystals to grow completely at M _n ^PMMA =13,100 g/mol, and indicated their hindrance at higher molecular weights (here, M _n ^PMMA?=?17,100 g/mol). It was feasible to neutralize the mentioned hindrance through fabricating the channels with brushes having the highest hindrance (M _n ^PS?=?14,800 g/mol and M _n ^PMMA?=?17,100 g/mol), and altering the physical environment from homo- to mixed-brush morphology. The characteristics (thickness, tethering density, and domain size) of developed channels from a certain material, in all arrangements and in various channels were in good agreement with those of corresponding non-epitaxial single crystals grown under the same conditions.     

Synthesis of Fe3O4@SiO2@polymer nanoparticles for controlled drug release

Novel multifunctional nanoparticles containing a magnetic Fe₃O₄@SiO₂ sphere and a biocompatible block copolymer poly(ethylene glycol)-b-poly(aspartate) (PEG-b-PAsp) were prepared. The silica coated on the superparamagnetic core was able to achieve a magnetic dispersivity, as well as to protect Fe₃O₄ against oxidation and acid corrosion. The PAsp block was grafted to the surface of Fe₃O₄@SiO₂ nanoparticles by amido bonds, and the PEG block formed the outermost shell. The anticancer agent doxorubicin (DOX) was loaded into the hybrid nanoparticles via an electrostatic interaction between DOX and PAsp. The release rate of DOX could be adjusted by the pH value.     

Properties of a poly(ethylene glycol)-<Emphasis Type="Italic">block</Emphasis>-poly(<Emphasis Type="Italic">γ</Emphasis>-benzyl <Emphasis Type="SmallCaps">l</Emphasis>-glutamate)-<Emphasis Type="Italic">graft</Emphasis>-poly(ethylene glycol) copolymer membrane

Poly(ethylene glycol)-block-poly(γ-benzyl l-glutamate)-graft-poly(ethylene glycol) (PEG-block-PBLG-graft-PEG) copolymer was synthesized by the ester exchange reaction of PBLG-block-PEG copolymer with a PEG chain. Surface morphology of the PEG-block-PBLG-graft-PEG copolymer membrane was characterized by atomic force microscopy (AFM). Mechanical and chemical properties of the PEG-block-PBLG-graft-PEG copolymer membrane were investigated by tensile testing and contact angle testing. The effects of grafting ratio on the properties of PEG-block-PBLG-graft-PEG copolymer membrane were primarilly studied.     

Thermo-responsive block copolymers based on linear-type poly(ethylene glycol): Tunable LCST within the physiological range

Thermo-responsive block copolymers poly（ethylene glycol）-block-poly（N-acryloyl-2,2-dimethyl-1,3-oxazolidine）, PEG-b-PADMO,based on linear PEG were prepared via a versatile reversible addition-fragmentation chain transfer（RAFT） polymerization.PEG₂₂（M_w = 1000） was used as the hydrophilic component,whose dehydration was the main driving force for the phase transition of these copolymers,as demonstrated by the ¹H-NMR spectra.Their lower critical solution temperatures（LCSTs） could be tuned in the range of 20℃to 35℃,by adjusting the degree of polymerization（DP） of PADMO between 14-27.Furthermore,a sharp phase transition at ca.33℃,close to the physiological temperature with minimal hysteresis,was observed for the PEG₂₂-b-PADMO₁₄ copolymer.Moreover,excellent reversibility and reproducibility were displayed for the same copolymer over 10 cycles of repeated temperature change between 25℃（below the LCST） and 40℃（above the LCST）.