Upper Critical Solution Temperature Polymers Research Articles

Mathematical model for characterization of temperature-responsive polymers: A study on the rheological behavior of gelatin and poly(N-isopropylacrylamide)

This study introduces a mathematical model for detailed characterization of temperature-responsive polymers, focusing on critical temperature, viscosity, storage modulus, their rate of change in the transition region, flow behavior, and potential hysteresis. Applied to gelatin (GEL) and poly(N-isopropylacrylamide) (pNIPAm), the model analyzes their rheological responses across various temperatures. It was observed that gel's critical temperature is slightly above its polymer's lower critical solution temperature, and vice versa for upper critical solution temperature polymers. The critical temperature for GEL was 28 °C, as opposed to 37 °C for pNIPAm. While concentration changes affected these values, the contribution of tetramethylethylenediamine (typically used in combination with various initiators to start the polymerization reaction) was found to be insignificant. GEL exhibited significant hysteresis, unlike pNIPAm's rapid transition. Their storage modulus and viscosity showed a linear correlation with concentration, with deviations at high pNIPAm concentrations suggesting the influence of polymer interactions and crosslinking. These findings offer valuable insights for applications requiring temperature sensitivity.

Introducing UCST onto Chitosan for a Simple and Effective Single-Phase Extraction.

Upper critical solution temperature (UCST) polymers undergo their own collapsed structures to show thermoresponsive functions favoring controlled release systems, cell adhesion, including separation process, etc. Although the copolymerization of UCST monomers with other vinyl monomers containing a pendant group is a good way to introduce additional functions, uncertain UCST performance as well as extensive bio-related properties are always the points to be considered. To accomplish this, the present work proposes the application of polysaccharides, i.e., chitosan (CS), as the biopolymer backbone to conjugate with functional molecules and UCST polymers. The use of chain transfer agents, e.g., mercaptoacetic acid, in radical polymerization with UCST poly(methacrylamide) (PMAAm) via the CS/NHS (N-hydroxysuccinimide) complex allows the simple water-based modification. The further conjugation of mouse anti-LipL32 IgG monoclonal antibody (anti-LipL32 mAb) onto CS-PMAAm (CS-PMAAm-Ab) enables a selective binding of recombinant LipL32 (rLipL32) antigen (Ag) in the solution. The CS-PMAAm obtained not only shows the cloud point in the range of 10-30 °C but also the extraction of rLipL32 because of CS-PMAAm-Ab-Ag aggregation. The present work demonstrates how CS expresses UCST with additional antibody conjugated is feasible for a simple and effective Ag single-phase extraction.

Bidirectionally Modulating the Dissipative Phase Transition of UCST Polymers in a Programmable Manner Using Visible Light

AbstractDynamic phase transitions are important in living organisms for sustaining their adaptive structures and functions. The design of artificial dynamic systems using light as a noninvasive input fuel has gained significant interest to mimic such adaptive features. Here the development of light‐fueled dissipative phase transitions of upper critical solution temperature polymers by introducing pendant spiropyrans as photoactive units, is reported. The reversible open‐close photoisomerization of spiropyrans is designed to undergo either an enhancement or a decline of their net charge, which is subsequently used to regulate the electrostatic interactions between polymer chains, and ultimately shift their phase transition temperatures to either a lower or a higher direction. The degree and speed of such bidirectional shifting are flexibly modulated by manipulating the external illumination parameters or varying the compositions/concentrations of the polymers. The diametrically opposite transmittance changes driven by light are utilized to produce a series of complementary patterns and shapes for application in transient information storage and encryption with improved accuracy and security. This work offers a bidirectional spatiotemporal modulation of dissipative phase transitions of polymers using visible light that allows highly tunable and adaptable features shared with their natural counterparts.

Synergistic Approaches in the Design and Applications of UCST Polymers.

This review summarizes recent progress in the synergistic design strategy for thermoresponsive polymers possessing an upper critical solution temperature (UCST) in aqueous systems. To achieve precise control of the responsive behavior of the UCST polymers, their molecular design can benefit from a synergistic effect of hydrogen bonding with other interactions or modification of the chemical structures. The combination of UCST behavior with other stimuli-responsive properties of the polymers may yield new functional materials with potential applications such as sensors, actuators, and controlled release devices. The advances in this area provide insight or inspiration into the understanding and design of functional UCST polymers for a wide range of applications.

Upper critical solution temperature polymer assemblies via variable temperature liquid phase transmission electron microscopy and liquid resonant soft X-ray scattering

Here, we study the upper critical solution temperature triggered phase transition of thermally responsive poly(ethylene glycol)-block-poly(ethylene glycol) methyl ether acrylate-co-poly(ethylene glycol) phenyl ether acrylate-block-polystyrene nanoassemblies in isopropanol. To gain mechanistic insight into the organic solution-phase dynamics of the upper critical solution temperature polymer, we leverage variable temperature liquid-cell transmission electron microscopy correlated with variable temperature liquid resonant soft X-ray scattering. Heating above the upper critical solution temperature triggers a reduction in particle size and a morphological transition from a spherical core shell particle with a complex, multiphase core to a micelle with a uniform core and Gaussian polymer chains attached to the surface. These correlated solution phase methods, coupled with mass spectral validation and modeling, provide unique insight into these thermoresponsive materials. Moreover, we detail a generalizable workflow for studying complex, solution-phase nanomaterials via correlative methods.

Tailoring a UCST-LCST-pH Multiresponsive Window through a Single Polymer Complex of Chitosan-Hyaluronic Acid.

Multistimuli-responsive polymers are important for controlled release. Owing to the fact that these polymers are derived from vinyl-based monomers, their decoration with other molecules is limited. Polysaccharides, especially chitosan (CS) and hyaluronic acid (HA), are pH-responsive biopolymers, whose chemical structures contain reactive functional groups for feasible chemical modifications to obtain add-on functions. The present work demonstrates the introduction of polymers with upper critical solution temperature (UCST) and lower critical solution temperature (LCST) performances onto CS and HA, respectively. By simply varying the mole ratio between the CS-containing UCST polymer and the HA-containing LCST polymer along with adjusting the pH, a polymer system with a UCST-LCST-pH multiresponsive window can be obtained. This multiresponsive window enables us to control the encapsulation and release with repeatability as evidenced from a model study on lysozyme. The present work, for the first time, shows a simple approach to obtain multiresponsive biodegradable polymers through the formation of a single polymer complex to tailor a specific multiresponsive window.

Effect of Tm of blend components on the isothermal melt-crystallization process of PHB/PLLA blends investigated using spectroscopic imaging and DSC

The understanding of morphology and crystallization in biopolymer blends offers the ability to tune these properties for specific uses. In this study, the isothermal melt-crystallization process of poly (3-hydroxybutyrate) (PHB)/poly ( l -lactic acid) (PLLA) blends with different weight loadings and molecular weights was investigated using in-situ attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopic imaging and differential scanning calorimetry (DSC). When the isothermal crystallization temperature is constant, increasing the fraction of blend component with a lower T m results in the decreasing T m of both blend components, which is indicated in DSC thermograms. The reduced T m delays the crystallization of both blend components and then the restrained crystallization leads to a greater extent of phase separation, which is shown in ATR-FTIR spectroscopic images. Likewise, at a constant isothermal crystallization temperature, with the decreasing molecular weights of blend components, the miscibility of polymer blend should be enhanced because of the shift of the phase boundary in phase diagram to lower temperatures. However, the decreasing overall crystallization rate and the delay of crystallization indicated in the integrated absorbance profiles and the decreasing T m indicated in the DSC thermograms can be used to explain the greater extent of phase separation in the PHB/PLLA blend shown in the spectroscopic images. A phase diagram was prepared to show the effect of polymer molecular weight on the miscibility of PHB/PLLA blends. Thus, increasing the fraction of the blend component with a higher T m , choosing polymers with a higher molecular weight and decreasing the isothermal crystallization temperature have been demonstrated to be effective methods to promote the miscibility of upper critical solution temperature (UCST) crystallizable polymer blends. Moreover, it was concluded that in-situ ATR-FTIR spectroscopic imaging can be combined with integrated absorbance profiles and DSC thermograms to deepen the understanding of multicomponent polymer systems. • A phase diagram was prepared to show the effect of M w on the miscibility of PHB/PLLA blends. • Effective methods are found to promote the miscibility of UCST polymer blends during isothermal crystallization process. • Spectroscopic imaging can be combined with DSC thermograms to deepen the understanding of multicomponent polymer systems.

Upper critical solution temperature polymeric drug carriers

Stimuli-responsive polymers are widely used as drug carriers in therapeutic applications. Upper critical solution temperature (UCST) polymeric carriers undergo a phase transition from hydrophobic to hydrophilic under the stimuli of temperature, near-infrared light, microwave, etc., thereby achieving a much more complete drug release. UCST polymeric carriers have recently emerged great potentials for controlled drug release, such as UCST polymeric micelles and hydrogels for cancer treatments and UCST polymeric surfaces for wound treatments, etc.. In this review, we mainly focus on UCST polymeric drug carriers based on different forms in recent five years. Various UCST polymers are first summarized based on their different structures. Drug-loaded UCST polymeric micelles with different stimuli, including with or without photothermal agents, pH-responsive and self-monitoring polymeric micelles, and representative drug-loaded UCST polymeric surfaces, including UCST polymeric coatings and mesoporous silica with UCST polymeric “gate”, are introduced. Finally, drug-loaded UCST polymeric hydrogels are also discussed. This review aims to draw attention to the advantages of UCST polymeric drug carriers and promote their clinical practice.

NIR Activated Upper Critical Solution Temperature Polymeric Micelles for Trimodal Combinational Cancer Therapy.

The balance between drug efficiency and its side effects on normal tissues is still a challenging problem to be solved in current cancer therapies. Among different strategies, cancer therapeutic methods based on nanomedicine delivery systems have received extensive attention due to their unique advantages such as improved circulation and reduced toxicity of drugs in the body. Herein, we constructed dual-responsive polymeric micelles DOX&ALS@MFM based on an upper critical solution temperature (UCST) polymer to simultaneously combine chemotherapy, photothermal therapy (PTT), and photodynamic therapy (PDT). Amphiphilic block copolymer P(AAm-co-AN)-b-PEI-ss-PEG-FA with a critical point of 42 °C was able to self-assemble into polymeric micelles under physiological conditions, which further encapsulated anticancer drug doxorubicin (DOX) and photosensitizer ALS to obtain drug-loaded micelles DOX&ALS@MFM. Micelles aggregated at tumor sites due to folate targeting and an enhanced permeability retention (EPR) effect. After that, the high intracellular concentration of glutathione (GSH) and near-infrared (NIR) light prompted disassembly of the polymer to release DOX and ALS. ALS not only plays a role in PTT but also produces singlet oxygen, therefore killing tumor cells by PDT. Both in vitro and in vivo studies demonstrated the photothermal conversion and reactive oxygen species generation ability of DOX&ALS@MFM micelles, at the same time as the excellent inhibitory effect on tumor growth with NIR light irradiation. Thus, our research substantiated a new strategy for the biomedical application of UCST polymers in the cited triple modal tumor therapy.

Design of a UCST Polymer with Strong Hydrogen Bonds and Reactive Moieties for Facile Polymer-Protein Hybridization.

Polymer-protein hybrids have been extensively used in biomedical fields. Polymers with upper critical solution temperature (UCST) behaviors can form a hydrated coacervate phase below the cloud point (Tcp), providing themselves the opportunity to directly capture hydrophilic proteins and form hybrids in aqueous solutions. However, it is always a challenge to obtain a UCST polymer that could aggregate at a high temperature at a relatively low concentration and also efficiently bind with proteins. In this work, a UCST polymer reactive with proteins was designed, and its temperature responsiveness and protein-capture ability were investigated in detail. The polymer was synthesized by the reversible addition-fragmentation chain transfer (RAFT) polymerization of acrylamide (AAm) and N-acryloxysuccinimide (NAS). Interestingly, taking advantage of the partial hydrolysis of NAS into acrylic acid (AAc), the obtained P(AAm-co-NAS-co-AAc) polymer exhibited an excellent UCST behavior and possessed good protein-capture ability. It showed a relatively higher Tcp (81 °C) at a lower concentration (0.1 wt %) and quickly formed polymer-protein hybrids with high protein loading and without losing protein bioactivity, and both the polymer and polymer-protein nanoparticles showed good cytocompatibility. All the findings are attributed to the unique structure of the polymer, which provided not only the strong and stable hydrogen bonds but also the quick and mild reactivity. The work offers an easy and mild strategy for polymer-protein hybridization directly in aqueous solutions, which may find applications in biomedical fields.

Upper Critical Solution Temperature Polymer Phase Transition as a Tool for the Control of Inorganic Salt Crystallization Process.

In this paper, the experimental research concerning the impact of the hydrophilic-hydrophobic transition of a polymer exhibiting the Upper Critical Solution Temperature (UCST) onto the crystallization process of inorganic salt is presented. A hypothesis was postulated that under favorable process conditions the sudden change of macromolecules properties and the resulting appearance of insoluble particles will induce the nucleation process of the salt. Since the transition point parameters may be precisely designed, the described mechanism would eliminate the stochastic nature of the crystallization process. Although performed experiments proved that the postulated process mechanism was incorrect, the presence of macromolecules had a significant impact on the crystallization course. The stochastic nature of the process was not eliminated; nevertheless, it seems that a specific point of nucleation was created which was independent of the cloud point temperature (TCP) of the polymer. Moreover, the surface morphology of crystals was changed.

Smart Self-Cleaning Membrane via the Blending of an Upper Critical Solution Temperature Diblock Copolymer with PVDF.

Poly(2,2,2-trifluoroethyl methacrylate)-b-poly(imidazoled glycidyl methacrylate-co-diethylene glycol methyl ether methacrylate) (PTFEMA-b-P(iGMA-co-MEO2MA)) containing an upper critical solution temperature (UCST) polymer chain was prepared and blended with poly(vinylidene fluoride) (PVDF) to produce a thermoresponsive membrane with smart self-cleaning performance. The successful preparation of the membrane was demonstrated by attenuated total reflection-Fourier-transform infrared spectroscopy, X-ray photoelectron spectroscopy, and scanning electron microscopy characterization. The membrane shows UCST performance, and its flux changes with the filtrate temperature as the UCST polymer chain stretches out and contracts in response to various temperatures. In addition, the UCST polymer chain can disrupt the foulant and push it away from the membrane when the temperature is above the UCST and thus enables membranes to exhibit a smart self-cleaning behavior. To the best of our knowledge, this work is the first report of a smart self-cleaning membrane based on the blending of a diblock copolymer containing a UCST polymer chain with PVDF.

Small dop of comonomer, giant shift of cloud point: Thermo‐responsive behavior and mechanism of poly(methylacrylamide) copolymers with an upper critical solution temperature

AbstractPoly(methylacrylamide) (PMAM) is a thermo‐responsive polymer with an upper critical solution temperature (UCST). Its cloud point (Tcp) is around 60 °C, unsuitable for certain biomedical and industrial applications. This study brought up a copolymerization strategy to tune the Tcp of PMAM with hydrophilic comonomers. Surprisingly, with a small portion of hydrophilic monomer doped, the Tcp of the PMAM copolymer can be significantly shifted. For instances, with ≤7 mol% of acrylamide or 1 mol% of oligo(ethylene glycol) methacrylate, the Tcp can be shifted in a wide range from ~69 to ~0 °C. Microdifferential scanning calorimetry demonstrated that the enthalpic effect during the phase transition of the solutions is indistinctive, while fluorescence measurement with pyrene as a probe revealed that the hydrogen‐bonding within polymer chains is enhanced by the hydrophobic aggregation of methyl groups. Therefore, the doped hydrophilic monomer could remarkably alter the ordering of water‐molecules and the extent for the aggregation of methyl groups, leading to the pronounced shifting in the Tcp of the copolymers. This work would facilitate the application of PMAM as smart polymer materials and guide the inventions of functional materials based on UCST polymers.

Thermoresponsive icy road sign by light scattering and enhanced fluorescence

Prototype thermoresponsive icy road signs with light scattering and enhanced fluorescence using upper critical solution temperature polymer phase separation.

Polymethacrylamide—An underrated and easily accessible upper critical solution temperature polymer: Green synthesis via photoiniferter reversible addition–fragmentation chain transfer polymerization and analysis of solution behavior in water/ethanol mixtures

AbstractWithin the group of stimuli‐responsive, “smart” materials, upper critical solution temperature (UCST) polymers remain sparsely investigated. Thus, this work focusses on a vastly ignored UCST polymer: polymethacrylamide (PMAAm). A cost‐efficient photoiniferter reversible addition–fragmentation chain transfer (RAFT) polymerization yielding narrowly dispersed (Đ < 1.1) PMAAm is presented. This PMAAm exhibits highly thermoreversible UCST‐type phase transitions (PT) in water/ethanol mixtures (ethanol content: 17–35 wt%) which are investigated via temperature dependent dynamic light scattering (DLS). Apart from the ethanol content, the PT temperature is affected by polymer mass fraction and chain length and varies between 10–80 °C depending on the three mentioned parameters. Lastly, PMAAm's propensity towards amide hydrolysis and concomitant PT‐suppression is investigated. Below temperatures of 40 °C, PMAAm solutions show no sign of amide hydrolysis for at least three days, however, if heated to 70 °C, the thermoresponsiveness gradually degrades within hours.

UCST-Type Copolymer through the Combination of Water-Soluble Polyacrylamide and Polycaprolactone-Like Polyester.

Copolymers of acrylamide (AAm) and hydrophobic monomers are known as non-ionic polymers to show an upper critical solution temperature (UCST) in aqueous solution. By utilizing cyclic ketene acetals and carrying out the radical ring opening polymerization along with copolymerization with AAm, a UCST polymer, poly(acrylamide-co-2-methylene-1,3-dioxepane) (P(AAm-co-MDO)), is obtained. The AAm/MDO content results in the shift of UCST phase transition temperature. The present work shows how the combination of water-soluble PAAm and polycaprolactone-like structured PMDO develops a new type of thermoresponsive polymer which can be expected for bio-related applications.

Preparation and Properties of UCST‐Type Thermoresponsive Polypeptide Bearing Amide Pendants

AbstractThermoresponsive polypeptides bearing amide pendants with an upper critical solution temperature (UCST) under physiologically relevant solution conditions are developed. A series of poly(γ‐propanyl‐l‐glutamate)s bearing amide pendants (PPLGn‐Am) with different molecular weight (or degree of polymerization, DP) is prepared by copper mediated 1,3‐dipolar cycloaddition. While fourier transform infra‐red and CD analysis reveal random coil conformation of the PPLGn‐Am in the solid‐state and in aqueous solutions, respectively, PPLGn‐Am shows reversible UCST‐type phase behaviors in deionized water (DI) water and phosphate‐buffered saline. Variable temperature UV–vis spectroscopy indicates that the UCST‐type cloud point temperature (Tcp) in the range of 25–75 °C can be readily tuned by molecular weight (or DP), polymer concentration, and incorporation of hydrophobic (i.e., n‐hexyl) pendants. Moreover, PPLGn‐Am is readily degraded by proteinase K within 48 h. The results indicate that UCST‐type thermoresponsive and biodegradable polypeptides in aqueous solutions can be constructed by conjugation of amide pendants which shall provide guidance for future UCST polymer designs.

Tunable UCST thermoresponsive copolymers based on natural glycyrrhetinic acid

Water-soluble thermoresponsive polymers present either upper critical solution temperature (UCST) or lower critical solution temperature (LCST) depending on the location of their miscibility range with water at high temperatures or at low temperatures. Compared with LCST polymers, the water-soluble UCST polymers are still less explored until now. In this work three copolymers of P(AAm-co-GAA) were synthesized by copolymerizing two acrylamide monomers, acrylamide (AAm) and acrylamide functionalized with natural glycyrrhetinic acid (GAA), using reversible addition-fragmentation chain transfer (RAFT) polymerization. These copolymers exhibited the typical UCST thermoresponsive behavior, and their phase transition temperatures could be easily tuned to around 37 °C for potential biological applications. Moreover, the UCST of P(AAm-co-GAA) can be adjusted not only by the content of glycyrrhetinic acid (GA) and polymer concentrations, but also by the host-guest interactions between GA and cyclodextrins (β- and γ-CD). The suitable value of UCST and the biocompatible nature of GA and CDs may endow these copolymers with practical applications in biomedical chemistry

NIR-Activated "OFF/ON" Photodynamic Therapy by a Hybrid Nanoplatform with Upper Critical Solution Temperature Block Copolymers and Gold Nanorods.

Photodynamic therapy (PDT) is a promising treatment modality for cancer treatment owing to its minimally invasive nature and negligible drug resistance. However, the disadvantages of conventional photosensitizers including universal aggregation-caused quenching (ACQ) effect or nonselective activation are still major hurdles for PDT clinical application. Herein, a new strategy for flexible manipulating photosensitizers in effective quenching and quick recovery of photoactivation is presented by introducing porphyrin units into upper critical solution temperature (UCST) block copolymer decorated gold nanorods (AuNR-P(AAm-co-AN-co-TPP)-b-PEG). The UCST block copolymer can achieve a self-quenching effect to make the porphyrin photosensitizers in the "Off" state by π-π stacking and hydrogen bonding interactions at physiological temperature, which greatly minimizes the nonselective phototoxicity of the photosensitizers to meet the requirement of phototherapy protected from sunlight. After the immigration of AuNR-P(AAm-co-AN-co-TPP)-b-PEG nanoparticles into the tumor tissue and the internalization by cancer cells, the UCST polymer chains can be extended under the local heating of AuNRs by NIR light irradiation, and then porphyrin photosensitizers are turned "On" to dramatically boost the PDT efficiency. Therefore, the process of PDT could be well manipulated in the "Off/On" state by the hybrid nanoplatform with UCST block copolymers and AuNRs, which will open new horizons for clinical treatments of PDT.

Upper critical solution temperature polymer-grafted hollow mesoporous silica nanoparticles for near-infrared-irradiated drug release.

Near-infrared (NIR) irradiation responsive drug delivery systems have many advantages, which have attracted extensive interest from researchers. In this study, a NIR-triggered drug release system was established by grafting upper critical solution temperature (UCST) polymers on the surface of hollow mesoporous silica nanoparticles (HMSNs) followed by treatment with the photothermal conversion agent indocyanine green (ICG). The as-prepared UCST polymers showed the clearing temperature of 45 °C, which were advantageous to serve as gatekeepers in the physiological environment (37 °C). Under NIR irradiation, the temperature of the solution was elevated above the clearing point due to the presence of ICG; consequently, the collapsed UCST polymer chains became more hydrophilic; this resulted in the exposure of the mesoporous channels of the HMSNs and achievement of a burst drug release. Moreover, this NIR-responsive delivery system showed good biocompatibility and high anticancer efficiency towards the MCF-7 cancer cells upon exposure to NIR irradiation. In addition, a synergistic effect of thermal and chemo treatment has been achieved by the application of NIR irradiation since cancer cells are more vulnerable to high temperatures than normal cells.