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Near-infrared light (NIR) triggered transdermal drug delivery systems are of great interest due to their on-demand drug release, which enable to enhance drug treatment efficiency as well as reduce side effect. Herein, a NIR-triggered microneedle (MN) patch array has been fabricated through depositing the photothermal conversion agent and anti-diabetic drug-loaded polymer vesicles with upper critical solution temperature (UCST) into dissolvable polymer matrix. The UCST-type polymer has a clearing point temperature of 41 °C and the drug-loaded polymer vesicles present excellent NIR-triggered and temperature responsive drug release behavior in vitro due to the disassociation of polymer vesicles upon NIR irradiation. After applying MNs to diabetic rats, significant hypoglycemic effect is achieved upon interval NIR irradiation and the blood glucose concentration can decrease to normal state for several hours, which enables to achieve the goal of on-demand drug release. This work suggests that the NIR-triggered MN drug release device has a potential application in the treatment of diabetes, especially for those requiring an active drug release manner.

Di- and triblock betaine copolymers composed of a sulfobetaine with a carboxy/phosphobetaine were synthesized by one-pot aqueous reversible addition-fragmentation chain transfer (RAFT) polymerization. The betaine methacrylate monomers were fully converted at each step by tuning the concentrations of the monomers, the chain transfer agent, and the initiator. AB-type diblocks poly(carboxybetaine methacrylate)-b-poly(sulfobetaine methacrylate) (PGLBT-b-PSPE) and poly(2-(methacryloyloxy)ethyl phosphorylcholine)-b-poly(sulfobetaine methacrylate) (PMPC-b-PSPE) were prepared to have identical unit numbers with different total molecular weights. Unlike homo-polysulfobetaine solutions or PGLBT-b-PSPEs in our previous report, the aqueous solutions of those diblock copolymers showed weak upper critical solution temperature (UCST) behavior, monitored by transmittance/dynamic light scattering. Even at the lowest temperature, the diblock chains remained in the unimer/aggregate polydisperse state, which is the intermediate stage prior to the emergence of monodisperse micelles. It is thought that the UCST behavior that originated from electrostatic attraction among PSPE motifs was interfered by temperature-inert motifs (PGLBT/PMPC) on the opposite side, having nearly the same unit number. The BAB-type triblock copolymer PSPE-b-PGLBT-b-PSPE with a 1:1:1 stoichiometry showed a clearer transmittance shift and size variation due to the increased ratio of PSPE at both chain ends. While the transmittance gradually decreased by cooling, larger aggregates (~ 700 nm) than those of diblocks (~ 180 nm) emerged with unimers. The small-large diffusive modes transformed into a monodisperse mode at much lower temperatures, which is assumed to be flower-like micelles consisting of PGLBT-loop coronas and PSPE core. However, another sample of 1:2:1 stoichiometry showed incomplete transition as diblocks having a similar AB ratio.

Creating stimulus-responsive materials solely by controlling polypeptide secondary nanostructures is challenging. We synthesized a methyl poly(ethylene glycol)-b-poly(O-benzyl-L-threonine) (mPEG-PBnLT) diblock copolymer that exhibited gel-to-sol UCST (Upper Critical Solution Temperature) transition behavior in an aqueous solution. The transition temperature window was easily adjusted by changing the copolymer concentration or length of the PBnLT block. Disassembly of the initial β-sheet nanoassemblies caused nanofibril transformation to spherical aggregates with increasing temperature, resulting in a gel-to-sol UCST transition. This result inspires a brand-new strategy for the structural design and functional control of materials. A novel thermoresponsive diblock copolymer of methyl poly (ethylene glycol)-b-poly (O-benzyl-L-threonine) was synthesized. The copolymer solutions exhibited gel-to-sol UCST transition behavior with temperature. The gel-to-sol transition was due to the disassembly of the initial β-sheet layered nanoassemblies that induced the transformation of self-organized morphology from nanosized fibrils to spherical aggregates.

Polyelectrolyte complexes (PECs) are recently observed to possess diversified thermoresponsive phase transition behaviors in aqueous solutions. Herein, by adjusting the initial polymer concentrations (

Herein we report the reversible addition–fragmentation chain transfer (RAFT) solution polymerization of tert-octyl acrylamide (OAA) in 1,4-dioxane using a trithiocarbonate-based RAFT agent. POAA homopolymers were synthesized with good control (Mw/Mn < 1.22) within 1 h at 70 °C when targeting mean degrees of polymerization (DP) of up to 100. Differential scanning calorimetry studies conducted on a series of five POAA homopolymers indicated a weak molecular weight dependence for the glass transition temperature (Tg), which varied from 67 to 83 °C for POAA DPs ranging from 22 to 99. High blocking efficiencies were observed when chain-extending such homopolymers with OAA, suggesting that most of the RAFT end-groups remain intact. Subsequently, we employed POAA as a steric stabilizer block for the PISA syntheses of spherical nanoparticles in n-heptane via RAFT dispersion polymerization of N,N-dimethylacrylamide (DMAC) at 70 °C. Targeting PDMAC DPs between 50 and 250 resulted in reasonably good control (Mw/Mn ≤ 1.42) and produced well-defined spherical diblock copolymer nanoparticles (z-average diameters ranging from 23 nm to 91 nm, with DLS polydispersities remaining below 0.10) within 5 h. A facile one-pot synthesis route to near-monodisperse 36 nm diameter POAA82-PDMAC100 nanoparticles was developed in n-heptane that provided similar control over the molecular weight distribution (Mw/Mn = 1.19). Unfortunately, POAA85-PDMACx diblock copolymer nanoparticles tended to deform and undergo film formation prior to transmission electron microscopy (TEM) studies. To overcome this problem, ethylene glycol diacrylate (EGDA) was introduced towards the end of the DMAC polymerization. The resulting core-crosslinked POAA85-PDMAC195-PEGDA20 triblock copolymer nano-objects exhibited a relatively well-defined spherical morphology. Interestingly, the colloidal stability of POAA85-PDMACx diblock copolymer dispersions depends on the type of n-alkane. Spherical nanoparticles produced in n-heptane or n-octane remained colloidally stable on cooling to 20 °C. However, the colloidally stable POAA-PDMAC nanoparticles prepared at 70 °C in higher n-alkanes became flocculated on cooling. This is because the POAA steric stabilizer chains exhibit upper critical solution temperature (UCST)-type behavior in such solvents. Nanoparticle aggregation was characterized by variable temperature turbidimetry and dynamic light scattering experiments.

Polyampholytes, widely investigated for their distinct properties, are typically prepared via conventional polymerisation techniques. This results in an ensemble of polymer chains with variation in molecular parameters such as length, ratio of charged groups and monomer order, which could influence their behaviour. Here, uniform oligoampholytes with precisely positioned negatively charged carboxylate and positively charged ammonium side-chains were synthesised using an iterative solid-phase synthesis strategy based on thiolactone chemistry. The amine side-chains were initially introduced via an acrylate, resulting in an amino-functionalised β-thioester that was shown to be susceptible to transesterification and hydrolysis, even under ambient conditions. While increasing the spacer length between the β-thioester and amine functionality could slow down this undesired side-reaction, it could not be completely suppressed. On the other hand, a tertiary amine-bearing vinyl sulfonamide proved to be a viable, hydrolytically stable alternative to introduce this moiety. The resulting uniform oligoampholytes are soluble in water and show UCST-type thermoresponsive behaviour in 85 vol% isopropanol/water mixtures.

For a general responsive polymer exhibiting a thermoresponsive transition in a solvent at the upper critical solution temperature (UCST), the interaction between polymer chains and solvent molecules and the interaction among polymer chains are of vital importance. Here, a new thermoresponsive transition in liquid crystalline poly(11-(4-((E)-4-butylstyryl)phenoxy)undecyl methacrylate) (PMAS) is found. The liquid crystalline PMAS containing mesogen moieties of stilbene in the side chains with a controlled molecular weight and narrow molecular weight distribution is synthesized by reversible addition–fragmentation chain transfer (RAFT) polymerization, and it can undergo a sharp and reversible insoluble-to-soluble transition in the solvents toluene, 1,2,4-triethylbenzene, and 1,4-dioxane at an UCST ranging from 26.3 °C to 52.3 °C. Why and how PMAS undergoes a thermoresponsive solubility transition in solvents are revealed, and the conclusion that crystallization drives the thermoresponsive solubility transition is made. It is believed that the crystallization strategy may be utilized to design new thermoresponsive polymers.

A series of zwitterionic poly(sulfobetaine methacrylate)s (PSBMAs) with various N-substituents, including n-alkyl, cyclohexyl, 2-hydroxyethyl, and phenyl, was synthesized in order to elucidate the ...

Bioinspired thermoresponsive polymeric materials with tunable phase-transition behaviors are highly desirable for biomedical applications. Here, we reported a facile approach for the synthesis of both lower critical solution temperature (LCST) and upper critical solution temperature (UCST) types of thermoresponsive polypeptoids with tunable phase-transition temperature in the range of 29--55 °C. The introduction of alkyl groups and ethylene glycol (EG) units results in a controlled phase-transition behavior under fairly mild conditions. A very sharp transition (ΔT ≤ 1.5 °C) is observed by simply adjusting pH and the alkyl chain length. In particular, the carboxyl-containing polypeptoids display designable UCST behavior, which can be finely tuned in both water and methanol. All these features make the obtained polymers beneficial for practical applications. More interestingly, we demonstrate that the hydrophilic EG group behaves as an excellent regulator to tune the UCST behavior, while the hydrophobic alkyl residues show remarkable capability to regulate the LCST behavior of the system. We hope that such systematic structure-property studies will enable the design of smart polymer materials to meet the specific needs of future applications.

Polyetherimide (PEI) nanoparticles with the size range from about 200 nm to 1 μm were successfully prepared from a PEI/DMSO solution by a simplified cooling-down method. The formation of PEI nanopa...

We report the synthesis and studies of self-assembly in solution of two related polyferrocenyldimethylsilane (PFS) ABC triblock terpolymers (TTPs), in which the BC blocks are amphiphilic comb diblo...

It has been a significant challenge to prepare multiple-response hydrogels with both lower critical solution temperature (LCST) and upper critical solution temperature (UCST). This work reports the...

Radical ring-opening polymerization is a clever strategy to incorporate cleavable linkages into otherwise nondegradable vinyl polymers. However, conventional systems suffer from slow copolymerizati...

A controlled grafting modification starch exhibited tunable phase transition temperature in aqueous solution was prepared via reversible addition–fragmentation chain transfer (RAFT) polymerization and esterification reaction under mild condition. P(AM/AN) copolymer was grafted onto the starch backbone and endowed the grafted copolymer thermosensitivity. The molecular structure and composition of P(AM/AN) copolymers were characterized by gel permeation chromatography (GPC), FTIR, and NMR, indicating a structurally controllable side chain of the grafted copolymer. Results of X-ray diffraction (XRD) demonstrate that the crystallinity of grafted copolymer decreases compared with starch due to side chains destruct the structural regularity of starch. Scanning electron microscopy (SEM) images show that grafted copolymer displays a rough, multilayer, and irregular morphology. Dynamic light scattering (DLS) and UV tests indicate that the grafted copolymer forms aggregates in aqueous solution and the UCST of the grafted copolymer is dependent on percent grafting (PG) and molecular interactions of side chains.

Microfiltration membranes have been obtained from polymethylpentene by phase separation of its dioctyl sebacate solutions under cooling. The dissolution of the polymer was carried out at its melting point followed by formation of membrane precursors in the form of films from the resulting solution, which were then cooled and washed with acetone to remove the ester and pore formation. Using laser interferometry, it is shown that the phase diagram of the polymethylpentene–dioctyl sebacate system corresponds to amorphous separation with the UCST. The rheology of solutions is studied by rotational rheometry, and it found that the logarithm of viscosity decreases linearly with increasing concentration of dioctyl sebacate. According to calorimetry, dioctyl sebacate plasticizes polymethylpentene, reducing its crystallinity. Treatment of the resulting films with acetone leads to the complete extraction of dioctyl sebacate, and, at its concentration of 25–45 wt %, a through porous structure is formed. This procedure makes it possible to obtain fairly strong membranes with a water permeability of 16.4 kg/(m2 h atm) and a retention coefficient of submicron particles with a diameter of 240 nm equal to 80%.

Temperature-responsive (or thermoresponsive) polymers belong to the most studied class of smart polymers and are mainly classified into two types based on their temperature-responsive behavior: lower critical solution temperature (LCST) and upper critical solution temperature (UCST). Based on polymeric design, when two temperature-responsive segments are connected through a covalent bond at each chain end, the block copolymers are expected to show a dual-temperature-responsive property upon conformational changes. Moreover, in recent years, multi-temperature-responsive properties that can represent complex states/structures have been reported. These multi-temperature-responsive block copolymers can set the stage for development in various research fields, such as drug-delivery carriers, sensors in solvents, model proteins, and memory storage. This review focuses on current multi-temperature-responsive polymeric materials and their applications and is divided into three parts: (1) dual-temperature-responsive block copolymers, (2) dual-temperature-responsive hydrogels, and (3) multi-temperature-responsive block copolymers. Temperature-responsive (or thermoresponsive) polymers belong to the most studied class of smart polymers and are mainly classified into two types based on their temperature-responsive behavior: lower critical solution temperature (LCST) and upper critical solution temperature (UCST). Based on polymeric design, when more than two temperature-responsive segments are connected through a covalent bond, the block copolymers are expected to show a multi-temperature-responsive property upon conformational changes. This review focuses on current multi-temperature-responsive polymeric materials and their future applications such as drug-delivery carriers, sensors in solvents, model proteins, and memory storage.

Because of its multiresponsive behavior upon variation of pH value, temperature, and ionic strength, poly­(N,N-dimethylaminoethyl methacrylate) (PDMAEMA) is an attractive candidate for adaptive surface coatings, especially in the field of biomedical sensors. In the presented article, PDMAEMA Guiselin brushes (5–12 nm, dry thickness) were prepared by the grafting-to approach, and the thermoresponsive UCST-type (upper critical solution temperature) behavior of the generated films, induced by [Fe­(CN)6]3–, was demonstrated for the first time. To clarify the specific mechanism of the temperature responsiveness, the molecular interactions between polymer chains and complex ions were studied by in situ infrared spectroscopy and in situ ellipsometry, showing wavenumber shifts of the ν­(CN) band due to ion pairing as well as changes of the ν­(OH) band intensity due to swelling. Conclusively, experimental data suggest that the electrostatic interaction between the two components plays a significant role in the thermoresponsive behavior of PDMAEMA films. Using this knowledge, the UCST of the PDMAEMA Guiselin brushes could be adjusted between 34.0 ± 1.2 °C at pH 8 and 40.7 ± 2.0 °C at pH 5.

While lower critical solution temperature (LCST)-type thermosensitive nanogels have been intensively studied, the upper critical solution temperature (UCST)-type versions are much less explored. This communication reports a method for the synthesis of zwitterionic UCST nanogels by reversible addition-fragmentation chain transfer (RAFT) polymerization-induced self-assembly in water-organic solvent mixtures. The nanogels were prepared by RAFT polymerization of 3-dimethyl(methacryloyloxyethyl)ammonium propanesulfonate, whose polymer is known to exhibit UCST behavior in water, conducted in ethanol-water mixtures at 70 °C using poly(poly(ethylene glycol) methyl ether methacrylate) as a macro-chain transfer agent (CTA) and a difunctional monomer as cross-linker. At a sufficiently high ethanol content in reaction media, spherical hairy nanogels with a single size distribution were obtained. These nanogels exhibited reversible heating-induced swelling and cooling-induced shrinking, consistent with the expected UCST behavior. The hydrodynamic size, volume changing ratio, and transition temperature of nanogels can be tuned by varying ethanol content in solvent mixtures, molar ratio of monomer-to-macro-CTA, and amount of cross-linker. Hairy nanogels were also successfully synthesized using a water-THF mixture as medium. The use of water-organic solvent mixtures as reaction media allowed for facile incorporation of a hydrophobic fluorescent monomer to make functional UCST nanogels.

Polymers showing an upper critical solution temperature (UCST) in aqueous solution were not rare, but the UCST was rarely observed under practically relevant conditions. Recently, much progress has been made in the synthesis of polymer systems that display UCST behavior under mild and physiologic conditions. Current developments focus on polymers that rely on hydrogen bonding. This viewpoint explains the historical context, presents the major properties, and concludes with a discussion of the most recent examples.

Thermoresponsive gels of the upper critical solution temperature (UCST) type shrink below their critical temperature and swell above it. Changes in water uptake by these gels are driven by thermally induced dissociation of hydrogen or ionic bonds between chains. A simple model is developed for the description of the equilibrium swelling of thermophilic gels with hydrogen bonds. To confirm its ability to describe observations, equilibrium swelling diagrams are fitted on poly(acrylamide-acrylic acid) and poly(acrylamide-acrylonitrile) macroscopic gels and microgels with various structures (copolymer gels, gels with interpenetrating networks, nanocomposite gels), as well as on biocompatible poly(N-acryloyl-glycinamide) and poly(allylurea-co-allylamine) gels. Numerical simulation reveals that material parameters evolve consistently with molar fractions of crosslinker, hydrophobic and hydrophilic comonomers in the feed, degree of ionization of functional groups, and concentration of nanofiller. It is shown that the model can also be applied to describe observations on thermophilic zwitterionic gels.

The mutual solubility of epoxy oligomer with polysulfone (PSU) and polyethersulfone (PES) was studied by optical interferometry. Additionally, phase diagrams (PDs) were plotted and their evolution during the curing process was shown. The phase structures of modified hardened systems, as well as their tensile strengths, elastic moduli, and crack resistance, have been studied by scanning electron microscopy and physico-mechanical techniques. The effect of initial components&rsquo, mutual solubility on the phase structure and, subsequently, on the physico-mechanical properties of the composite material is shown. Differences in the structure and properties of the cured modified compositions depending on the type of PD (with Upper Critical Solution Temperature (UCST) for PSU and Lower Critical Solution Temperature (LCST) for PES) of the initial components are shown.

The self-assembly of block copolymers constitutes a timely research area in polymer science with implications for applications like sensing or drug-delivery. In here, we investigate the unprecedented aggregation behaviour of high molecular weight block copolymer poly(N,N-diethylacrylamide)-b-poly(4-acryloylmorpholine) (PDEA-b-PAM) (Mn>400 kg/mol) in organic solvent tetrahydrofuran (THF). To elucidate the aggregation, dynamic light scattering, cryo transmission electron microscopy and turbidimetry were employed. The aggregate formation was assigned to the unprecedented upper critical solution temperature behaviour of PAM in THF at elevated concentration (> 6 wt%) and high molar masses. Various future directions for this new thermo-responsive block copolymer are envisioned, e.g. in the areas of photonics or templating of inorganic structures. This article is protected by copyright. All rights reserved

Indocyanine green (ICG) was incorporated into poly(ethylenimine)/(phenylthio) acetic acid (PEI/PTA) ion pair self-assembly (IPSAM) as a photosensitizer. PEI/PTA/ICG IPSAM was more stable against a thermal dissolution as the PTA and ICG content were higher. The zeta potential of the IPSAM without ICG (the amino group(A)/carboxyl group(C) molar ratio was 5.3:4.7) was a strong positive charge. Upon the addition of a small amount of ICG (A/C/ICG molar ratio was 5.3:4.7:0.01), it changed to a strong negative charge. The IPSAM on TEM micrographs was found as almost sphere-like nanoparticles and its diameter was around 50 nm. The doxorubicin-loaded IPSAM on CLSM micrographs was found as nano-sized circular red domains, indicating that the anti-cancer drug was successfully loaded in the IPSAM without disrupting the shape. When A to C molar ratio was 4:6, the ICG-incorporated IPSAM released its cargo appreciably under NIR irradiation even though the temperature of the IPSAM suspension could hardly reach the upper critical solution temperature (UCST) under NIR irradiation, suggesting that the release took place mainly by the radical oxygen species (ROS)-induced oxidation of PTA. When A to C molar ratio was 5.3:4.7, the temperature of the IPSAM suspension could reach the UCST under NIR irradiation and the release degree increased in proportion to the temperature increase, indicating the release took place mainly by the temperature change. According to the FT-IR spectroscopy, the NIR irradiation-triggered release could be attributed to the heat and ROS generated by ICG under NIR irradiation.

International audience; A new kind of near-infrared (NIR) light-responsive polymer nanogel is demonstrated. The micellar aggregates of an ABA-type triblock copolymer, whose core is a thermosensitive polymer displaying an upper critical solution temperature (UCST), are crosslinked using a photothermal nickel-bis(dithiolene) complex that absorbs NIR light and converts efficiently optical energy into heat. We show that when the nanogel aqueous solution is exposed to NIR light, even at a low power density of 0.16 W cm(-2)and a low nickel-bis(dithiolene) complex concentration of 61.4 mu g mL(-1), the photothermally induced heating is sufficient to allow the nanogel particles to undergo a volume phase transition. The induced volume increase due to the positive thermosensitivity of the polymer leads to the release of loaded hydrophobic dye molecules. Using an energy balance model, the photothermal conversion efficiency of the nickel-bis(dithiolene) complex in the nanogel was evaluated through solution temperature and transmittance measurements under NIR laser irradiation at various light power densities as well as different nanoparticle concentrations and solvents. The photothermal conversion efficiency can reach about 64%, which positions the nickel-bis(dithiolene) complex among the most efficient photothermal agents in the NIR spectral region around 1000 nm.

Dual thermo- and pH-responsive star polymers with tunable upper critical solution temperatures (UCST) were synthesized by an “arm-first” RAFT polymerization approach. Crosslinking took place in a single step involving polymerization of 3-dimethyl(methacryloyloxyethyl) ammonium propane sulfonate (DMAPS) mediated by a macroRAFT agent containing carboxylic end-group and in the presence of crosslinker N,N-methylenebis(acrylamide) (MBA). Varied-temperature turbidity analysis, dynamic light scattering (DLS) and rheology analysis revealed that the star-shaped PDMAPS had a smaller hydrodynamic volume while retaining fast response properties, compared with linearly-shaped PDMAPS. Meanwhile, zeta-potential was used to determine that the range of UCST regulated by pH was greatly expanded and proportional to the number of end-groups that could be generally manipulated through RAFT polymerization. By changing the pH values from 3 to 10, the adjustable UCST range of the star polymer solution can reach over 36 °C. These results demonstrate that the topological structure and end-group effect are able to manipulate the phase transition behavior of polyzwitterions. These materials offer great potential as additives or drug delivery vehicles in biomedical applications.

A dumbbell-shaped copolymer (PDMAEMA)4-PCL-SS-PCL-(PDMAEMA)4 with a lower critical solution temperature (LCST) and redox responses was first synthesized by the combination of ring opening polymerization (ROP), click chemistry and atom transfer radical polymerization (ATRP). Then a dumbbell-shaped copolymer (PDMAPS)4-PCL-SS-PCL-(PDMAPS)4 with an upper critical solution temperature (UCST) and redox responses was obtained through the quaternization reaction between DMAEMA and excess 1,3-propane sultone. Both (PDMAEMA)4-PCL-SS-PCL-(PDMAEMA)4 and (PDMAPS)4-PCL-SS-PCL-(PDMAPS)4 were amphiphilic, and they could self-assemble into spherical micelles under certain conditions. Benefitting from the LCST-type thermoresponse of PDMAEMA and UCST-type thermoresponse of PDMAPS, both dumbbell-shaped copolymers (PDMAEMA)4-PCL-SS-PCL-(PDMAEMA)4 and (PDMAPS)4-PCL-SS-PCL-(PDMAPS)4 presented temperature-responsive properties. The morphology and size of their assemblies would be changed when the temperature is altered. Meanwhile, due to the redox-response of disulfide bonds, both (PDMAEMA)4-PCL-SS-PCL-(PDMAEMA)4 and (PDMAPS)4-PCL-SS-PCL-(PDMAPS)4 showed redox-responsive properties. When DL-dithiothreitol (DTT) was added into the systems, disulfide bonds were broken, causing the change of (PDMAEMA)4-PCL-SS-PCL-(PDMAEMA)4 to PCL-(PDMAEMA)4, while (PDMAPS)4-PCL-SS-PCL-(PDMAPS)4 changed into PCL-(PDMAPS)4. The distributions of Rh for both (PDMAEMA)4-PCL-SS-PCL-(PDMAEMA)4 and (PDMAPS)4-PCL-SS-PCL-(PDMAPS)4 assemblies broadened with asymmetric peaks, giving rise to curves with double peaks. After 24 h, DLS curves became symmetric with a single peak, and the Rh was about half that of the original assemblies. In the meantime, dispersed spherical micelles could be observed by TEM.

Synthesis of polyampholytes based on cationic and anionic monomers that exhibit upper critical solution temperature (UCST) behavior is challenging as both the monomers need to be incorporated in stoichiometric amounts. By virtue of their charges, these polymers can exhibit special properties when both their ratios and/or the distance between the two charges are tuned. Here, the synthesis of alternating charge-neutral polyampholytes is described via reversible addition–fragmentation chain transfer (RAFT) statistical copolymerization of cationic styrenic and anionic N-substituted maleimide monomers. The percentage of N,N-dimethylaminomethylstyrene (DMAMSt) and N-carboxyethylmaleimide (CEMI) monomers in P(DMAMSt-alt-CEMI) copolymers is in 50/50 molar ratios, as confirmed by 1H NMR measurements during the polymerization of DMAMSt and tBuEMI monomers. The thermoresponsive UCST behavior of the obtained charge neutral polyampholytes is demonstrated in water and alcohol–water (methanol, ethanol and 2-propanol) solvent mixtures. Moreover, the effect of the charge neutral polyampholyte concentration on the UCST phase transition in ethanol/H2O solvent mixtures is discussed. The intermediate tert-butyl protected CEMI-based alternating copolymers P(DMAMSt-alt-tBuEMI) were found to be pH responsive and a diblock copolymer with a poly(N,N-isopropylacrylamide)block(PNIPAM-b-P(DMAMSt-alt-tBuEMI) demonstrated pH and LCST thermoresponsive behavior. These results demonstrate the use of these dual responsive polymers for future work on the exploration of these cationic and thermoresponsive polymers for the development of self-assembled responsive drug carriers.

Stimuli-responsive polymers with excellent biocompatibility and biodegradability are highly demanded as carriers for controlled drug delivery. Herein, a functional poly(e-caprolactone) (PCL) of poly(6-acetoxyl-e-caprolactone)-graft-(6-methyluracil) (PCCL-g-MU) was synthesized via post modification of poly(6-acetoxyl-e-caprolactone) (PCCL) with 6-(chloromethyl) uracil (MU). The incorporation of carboxyl and uracil groups endowed the PCL backbone with both pH and upper critical solution temperature (UCST) responsiveness. Benefiting from the structural similarity between MU and the anticancer drug 5-fluorouracil (5-FU), the self-assembled PCCL-g-MU nanoparticles resulted in a high 5-FU loading efficiency of 42%. Temperature-dependent release behavior of 5-FU loaded PCCL-g-MU nanoparticles was found to have originated from UCST transition. MTT assay against the L929 cell line revealed low cytotoxicity of PCCL-g-MU nanoparticles. The hydrolysis of the PCL backbone in either PBS or enzymatic solution indicated excellent biodegradability of PCCL-g-MU. It was demonstrated for the first time that biodegradable poly(e-caprolactone) with UCST behavior was developed, which is significant for enriching the thermo-responsive polymer library as well as biomedical applications.

A light-sensitive moiety, azobenzene, is incorporated into polyacrylamide (PAM) to yield copolymers with upper critical solution temperatures (UCST) in aqueous solutions. The thermoresponsiveness of the copolymers can be tuned not only by light irradiation, which causes the transition between the trans- and cis-forms of the azobenzene, but also by addition of α-cyclodextrin (α-CD), which preferentially complexes with the trans-form of azobenzene. The UCST transition is a combined effect of hydrogen bonding between the amide groups of the PAM chains and the hydrophobic interaction between azobenzene units, the latter of which can be influenced by the photoisomerization of azobenzene and the host–guest interaction between azobenzene and α-CD. The strategy of incorporating switchable hydrophobicity may inspire designs of UCST polymers, which may have potential applications as drug delivery devices and catalyst carriers.

Self-complementary supramolecular polymers (SCSPs), an efficient combination of sextuple hydrogen-bonded dimer moieties and a temperature-responsive polymer, can promote the construction of stable supramolecular polymer networks (SPNs) that enable the formation of well-defined nanospherical micelles in aliphatic alcohols. These micelles undergo tailorable, thermoresponsive phase transitions at the upper critical solution temperature (UCST) and have a desirable spherical morphology and size ranges, thus, are potential candidates for applications in interfacial engineering and biomedical fields. Moreover, concentration-dependent UCST measurements and variable-temperature experiments indicated that the hydrogen-bonded complexes are strong enough to form stable intermolecularly entangled SPNs within the micelles, even above the UCST or at low concentrations in solution, which enables the micelles to undergo reversible temperature-dependent conformational changes between insoluble and soluble globules without significant changes in particle size or size distribution. Thus, this newly discovered system offers a new approach toward the development of next-generation temperature-responsive SCSPs with the desired structural stability that undergoes UCST transitions.

The wide range of applications of poly(N-isopropylacrylamide) (PNIPAM) is based on the temperature dependence of its coil-to-globule transition, which strongly relies on the solvent. Here, we focus...

We investigated the thermoresponsive behavior of poly(acrylamide-co-acrylonitrile) (poly(AAm-co-AN)) with an upper critical solution temperature (UCST) in water to apply this polymer in cosmetic pr...

Multi‐l‐arginyl‐poly‐l‐aspartic acid (MAPA), also known as cyanophycin, can incorporate lysine into the side‐chain position of arginine when being prepared with recombinant Escherichia coli. The soluble fraction (sMAPA) is known to display both lower critical solution temperature (LCST) and upper critical solution temperature (UCST) responses at the physiological condition. In an attempt to alter the UCST thermal response, maltodextrin was employed to conjugate onto the amine group of lysine of sMAPA via the formation of Schiff base. In phosphate buffered saline, the UCST of the conjugates appeared around 50–62°C, depending on the extent of conjugation. In contrast to the unmodified sMAPA, the UCST of the conjugate became independent of pH ranging from 1 to 11. Heating the conjugate solution to complete transparent caused a delayed and partial recovery of the original turbidity during subsequent cooling. However, the turbidity can be restored by further precipitation with ethanol or isopropanol followed lyophilization and re‐dissolution. At room temperature, below UCST, the agglomerates exhibited a size of around 200–400 nm under TEM and DLS. © 2019 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2019, 57, 2048–2055

Zwitterionic sulfobetaine-containing diblock copolymer, poly(ethylene glycol)methyl ether-block-poly[3-dimethyl(methacryloyloxy ethyl)ammonium propane sulfonate] (MPEG-b-PSBMA), was successfully synthesized and utilized as a stabilizer to prepare mono- and bimetallic nanoparticles. Precursor poly(ethylene glycol)methyl ether-block-poly[2-(N-dimethylamino)ethyl methacrylate] (MPEG-b-PDMA) diblock copolymer was first synthesized via atom transfer radical polymerization. PDMA blocks were reacted with 1,3-propanesultone to obtain MPEG-b-PSBMA diblock copolymer. Spherical monometallic gold (Au), platinum (Pt) and bimetallic alloy gold/platinum (Au/Pt), gold/silver (Au/Ag), and silver/platinum (Ag/Pt) nanoparticles (with a diameter below 8.0 nm) were synthesized in aqueous media via sonochemical method using diblock copolymer as stabilizer. The zwitterionic sulfobetaine block copolymer provided thermodynamic (5 days at 65 °C) and kinetic (1 year at 25 °C) stability to the synthesized NPs without aggregation. Zwitterionic PSBMA blocks of MPEG-b-PSBMA diblock copolymer showed an upper critical solution temperature (UCST) in aqueous media. This thermo-responsive block copolymer provided better stabilization to metal NPs as compared with MPEG and PSBMA homopolymers. The structures of bi- and monometallic NP dispersions were characterized by measuring surface plasmon resonance and transmission electron microscopy. The prepared metal NP/polymer dispersions showed good catalytic activities (Ag/Pt > Au/Ag > Au > Au/Pt > Pt) in the reduction of p-nitrophenol to p-aminophenol.

A novel switchable luminescent thermometer based on thermo-responsive triblock copolymer poly(ethylene glycol)-b-poly(acrylamide-co-acrylonitrile-co-dimethylaminoethylmethacrylate) (PEO113-b-P(AAm264-co-AN112-co-DMA8)) and Eu-containing polyoxometalate (Eu-POM) was successfully constructed. The copolymer synthesized by RAFT exhibited a linear response to temperature variations in aqueous media, which was quite different from the uncharged copolymer P(AAm-co-AN) having a specific upper critical solution temperature (UCST). Eu-POM was surrounded around thermo-responsive blocks through electrostatic interactions, and its luminescence could be finely tuned due to the sensitivity of copolymer to the temperature variation. In cold water, POMs were trapped in highly hydrophobic cores, exhibiting an intense emission. With the upraising of temperature, the emission intensity presented a gradual decrease and showed a linear correlation with temperature. When the complex solution cooled down, the luminescence could also be perfectly restored. This temperature-luminescence correlation could be held for numerous trials, showing a potential application in thermometer.

Poly(acrylic acid) is water soluble but can be converted into a thermoresponsive polymer possessing an upper critical solution temperature (UCST) by copolymerizing with acrylonitrile. The copolymer...

A series of ABA-type triblock copolymers (PImBF4-b-PPG-b-PImBF4) comprising of poly(propylene glycol) (PPG) as middle block and UCST polypeptide on both sides of PPG was synthesized by ring-opening polymerization of γ-chloropropyl-L-glutamic acid-based N-carboxyanhydride (CPLG-NCA) and then side-chain modification including nucleophilic substitution of the chloro group followed by copper-mediated 1,3-dipolar cycloaddition and subsequent ion-exchange reaction. Variable-temperature UV–vis spectroscopy revealed that the upper critical solution temperature (UCST)-type cloud point temperature (Tcp) was highly dependent on both polypeptide and PPG chain length as well as polymer concentration. Increasing the polymer chain length or concentration frequently results in Tcp increases. Noticeable hysteresis in a cooling/heating cycle was observed for all resulting triblock copolymers owing to a slow disassembly of large aggregates (d = 145 nm) in the heating cycle. Moreover, the resulting UCST triblock copolymers were used to regulate the release property of ciprofloxacin (CIP)-loaded poly(vinyl alcohol) (PVA) hydrogel. The incorporation of PImBF4-b-PPG-b-PImBF4 hampered the burst release of CIP at 37 °C indicating their potential toward sustained release of drug-loaded hydrogels.

Thermo, pH, and photo triple-responsive hollow nanospheres self-assembled from amphiphilic random copolymer poly (styrene-stat-4-vinylpyridine) (PS-stat-P4VP) and azobenzene (AZO) 4-phenylazophenol have been investigated by means of TEM, SEM, FTIR, DLS and UV–vis spectrophotometry. Controlling over the ratio of PS-stat-P4VP and AZO can realize different size of hollow nanospheres. PS-stat-P4VP/AZO hollow nanospheres display UCST behavior and perform well reversible self-assembly and disassembly property between 25 °C and 45 °C as well as pH = 2.7 and pH = 8.1. Besides, the hollow nanospheres can be significantly elongated along the polarization direction of the polarizer, showing well photo-responsive performance. With the UCST of about 37 °C and pH responsive range close to human body, those PS-stat-P4VP/AZO hollow nanospheres demonstrate great potential in medicine and physiology.

Premature and incomplete drug release is the typical bottleneck of drug release in traditional chemotherapy. Synergistic therapies are highly desirable in medicine and biology because they can compensate for the drawbacks of single therapy and significantly enhance the therapeutic efficacy. Herein, a novel near infrared (NIR)-activated polymeric nanoplatform with upper critical solution temperature (UCST) was constructed for image-guided synergistic photothermal therapy (PTT) and chemotherapy. UCST-responsive amphiphilic block copolymers were synthesized by reversible addition-fragmentation chain-transfer (RAFT) polymerization and then co-assembled with IR780 and cabazitaxel (Cab) to form spherical nanoparticles (NPs). IR780/Cab dual-loaded UCST polymeric NPs can produce local heating upon NIR laser irradiation and further lead to the dissociation of cargo-loaded NPs and controlled release of Cab. IR780 plays the role of both a heating generator and an activator for "on-demand" drug release. The investigation of in vivo fluorescence and photothermal imaging clearly demonstrated tumor targeting. Notably, both in vitro and in vivo studies illustrated that the synergistic PTT and chemotherapy presented better anticancer efficacy than that of PTT and chemotherapy simplely combined. Thus, the well-defined polymeric nanoplatform opens a versatile and effective path to develop image-guided synergistic therapies for tumor treatment.

Novel multiresponsive hybrid biocompatible systems of κ-carrageenan-graft-poly(2-isopropyl-2-oxazoline-co-2-butyl-2-oxazoline)s with unique combination of responsiveness to external stimuli were synthesized and studied. The polymer thermoresponsive behavior proved the existence of both lower and upper critical solution temperatures in aqueous milieu, forming gel at lower temperature, a solution at room temperature and cloudy nanophase-separated dispersion at elevated temperature. The limit temperatures can easily be adjusted by the polyoxazoline graft length and grafting density. Moreover, the polymer behavior is additionally dependent on the concentration of potassium ions. The polymers behave similarly as the original κ-carrageenan, and thus, the poly(2-alkyl-2-oxazoline) grafts do not decrease the ability of the κ-carrageenan to form the self-assembled structures. Molecular principles beyond this multistimuli-responsive behavior were elucidated with the use of dynamic light scattering, magnetic resonance and fluorescence measurements as well as atomic force microscopy. These polymers could be used in a wide range of biological applications demanding thermo- and potassium-responsiveness.

An acrylic block copolymer system is a promising candidate for the functional adhesives bearing good weatherability as well as high transparency. Coated layers of the acrylic block copolymers were prepared by the solution coating method using a polymethylmethacrylate-block-poly(n-butylacrylate)-block-polymethylmethacrylate triblock copolymer (MAM) and a polymethylmethacrylate-block-poly(n-butylacrylate) diblock copolymer (MA). The thickness of the prepared specimens was 50 μm, which is typical of the pressure-sensitive adhesives. Atomic force microscope (AFM) observations and two-dimensional small-angle X-ray scattering (2d-SAXS) measurements were performed to analyze the nano structures and to discuss the effects of the drying temperature on the nano structures. Note that better physical properties were obtained in the specimen prepared at the lower drying temperature. The AFM observations revealed cylindrical morphology for the annealed MAM neat specimen. On the other hand, the 2d-SAXS measurements revealed spherical morphology for all of the specimens including MAM neat and MA/MAM blends. The effects of the drying temperature on the ordering regularity of spheres, d spacing, and radius of sphere has been examined quantitatively. It was found that the ordering regularity of spheres was more improved for the higher drying temperature. As for the behaviors of d and R, the experimental results exhibited very complicated behaviors as a function of the drying temperature. Namely, d and R increased as a function of the drying temperature, which is completely opposite to the general behaviors of the block copolymer microdomain structure as d or R ∝ T −1/3 for the upper critical solution temperature system where the interaction between two kinds of the constituent block chains is decreased with an increase in temperature. The effect of structure freezing during the solvent evaporation was taken into account and such complicated behaviors of experimental results (d and R) could be almost perfectly explained. It is concluded by this study that the poor regularity of the sphere ordering provides softer property with larger elongation at break for the coated film, which is more suitable as the pressure-sensitive adhesives.

Poly(acrylic acid-co-acrylamide) (P(AA-co-AM)) hydrogels with upper critical solution temperature (UCST) were synthesized via radical copolymerization technology, which were then incorporated with SiO2@polypyrrole (SiO2@PPy) for the construction of light-, thermo- and pH-responsive drug delivery system. The synthesized SiO2@PPy@P(AA-co-AM) hydrogels were then examined by Fourier transform infrared (FT-IR) spectrometry, field emission scanning electron microscopy (FESEM), thermogravimetry (TG) and differential thermogravimetric (DTG). Finally, the designed SiO2@PPy@P(AA-co-AM) hydrogels were used for controlled delivery of 5-fluorouracil (5-FU), an anti-cancer drug. An encapsulation ratio of up to 92.2% was obtained when 5-FU was encapsulated in the SiO2@PPy@P(AA-co-AM) hydrogels, and the cumulative release of 5-FU could reach 83.9% with the near-infrared (NIR) irradiation of 6 h at pH 7.4. During the controlled release of 5-FU, PPy in the system could convert the NIR irradiation to heat as a photo-thermal transducer while maintaining the temperature in the UCST range of P(AA-co-AM). In addition, SiO2 in the hydrogels acted as a gatekeeper to prevent the burst release of 5-FU.

Temperature variations may induce changes in solution properties for thermoresponsive polymers, which have drawn much research attention due to their potential applications in different areas. To meet the practical requirements, rational design of the polymers is important and necessary. We reviewed literature in this field and proposed a thermodynamic map to guide the design of such polymers. The map is drawn up based on the enthalpic and entropic contributions (ΔHm and ΔSm) to the free energy change of mixing (ΔGm). The map is divided into four zones: soluble, insoluble, upper critical solution temperature (UCST), and lower critical solution temperature (LCST), with two lines representing the freezing and boiling points of the solvent (water) as two boundaries for the UCST and LCST zones. With the help of such a map, we attempt to illustrate how the UCST and LCST are affected by the various interactions in polymer-water mixtures, such as hydrophobic and ionic interactions, and hydrogen bonding, so that the thermoresponsive properties of a polymer can be predicted according to their molecular structures. The critical temperatures UCST and/or LCST of a polymer can be obtained from the slope of the straight line that passes through the original point and the location of the polymer on the map. Examples in the literature are shown to fit in different zones of this map, and we also demonstrate how the variations of the chemical composition or the molecular structure of the polymers can change the intra- and inter-molecular interactions involved, which in turn change the solution properties of the polymers and induce changes in the critical solution temperatures. This map may be used in the design and preparation of thermoresponsive polymers with UCST and LCST on demand.

Interdiffusion and phase equilibrium in the system composed of polystyrene and statistical copolymers of butyl acrylate and styrene were studied by optical interferometry. The diagrams of the phase state were for the first time plotted and analyzed; pair interaction parameters were determined. The obtained diagrams are characterized by an upper critical solution temperature (UCST). The dependence of the interaction parameter on copolymer composition, polystyrene molecular weight, and temperature was shown. The data of interdiffusion of polystyrene into copolymers (and vice versa) are presented; they vary within 10–7–10–11 cm2/s. The activation energy of diffusion was calculated. No influence of structural heterogeneity of macromolecules of statistical copolymers on phase characteristics, translational diffusion coefficients, and coordinate of the diffusion front was registered.

Gelatin is used widely in the biomedical field, among other for wound healing. Given its upper critical solution temperature, crosslinking is required. To this end, gelatin is chemically modified with different photo-crosslinkable moieties with low (32-34%) and high (63-65%) degree of substitution (DS): gelatin-methacrylamide (gel-MA) and gelatin-acrylamide (gel-AA) and gelatin-pentenamide (gel-PE). Next to the more researched gel-MA, it is especially interesting and novel to compare with other gelatin-derived compounds for the application of wound healing. An additional comparison is made with commercial dressings. The DS is directly proportional to the mechanical characteristics and inversely proportional to the swelling capacity. Gel-PE shows weaker mechanical properties (G' < 15 kPa) than gel-AA and gel-MA (G' < 39 and 45 kPa, respectively). All derivatives are predominantly elastic (recovery indices of 89-94%). Gel-AA and gel-MA show excellent biocompatibility, whereas gel-PE shows a significantly lower initial biocompatibility, evolving positively toward day 7. Overall, gel-MA shows to have the most potential to be applied as wound dressing. Future blending with gel-AA to improve the curing kinetics can lead to dressings able to compete with current commercial dressings.