Temperature-responsive Block Copolymers Research Articles

Multifunctional Self-Assembled Block Copolymer/Iron Oxide Nanocomposite Hydrogels Formed from Wormlike Micelles.

This article reports the preparation of multifunctional magnetic nanocomposite hydrogels formed from wormlike micelles. Specifically, iron oxide nanoparticles were incorporated into a temperature responsive block copolymer, poly(glycerol monomethacrylate)-b-poly(2-hydroxypropyl methacrylate) (PGMA-b-PHPMA), and graphene oxide (GO) dispersion at a low temperature (∼2 °C) through high-speed mixing and returning the mixture to room temperature, resulting in the formation of nanocomposite gels. The optimal concentrations of iron oxide and GO enhanced the gel strength of the nanocomposite gels, which exhibited a strong magnetic response when a magnetic field was applied. These materials retained the thermoresponsiveness of the PGMA-PHPMA wormlike micelles allowing for a solid-to-liquid transition to occur when the temperature was reduced. The mechanical and rheological properties and performance of the nanocomposite gels were demonstrated to be adjustable, making them suitable for a wide range of potential applications. These nanocomposite worm gels were demonstrated to be relatively adhesive and to act as strain and temperature sensors, with the measured electrical resistance of the nanocomposite gels changing with applied strain and temperature sweeps. The nanocomposite gels were found to recover efficiently after the application of high shear with approximately 100% healing efficiency within seconds. Additionally, these nanocomposite worm gels were injectable, and the addition of GO and iron oxide nanomaterials seemed to have no significant adverse impact on the biocompatibility of the copolymer gels, making them suitable not only for 3D printing in nanocomposite engineering but also for potential utilization in various biomedical applications as an injectable magnetic responsive hydrogel.

Synthesis of thermo-responsive polymer gels composed of star-shaped block copolymers by copper-catalyzed living radical polymerization and click reaction

ABSTRACT In recent times, there has been a significant surge in research interest surrounding thermo-responsive water-soluble polyacrylamides, primarily due to their intriguing capability to undergo significant solubility changes in water. These polymers exhibit the remarkable ability to shift from a soluble to an insoluble state in response to temperature variations. The capacity of these polymers to dynamically respond to temperature changes opens up exciting avenues for designing smart materials with tunable properties, amplifying their utility across a spectrum of scientific and technological applications. Researchers have been particularly captivated by the potential applications of thermo-responsive water-soluble polyacrylamides in diverse fields such as drug delivery, gene carriers, tissue engineering, sensors, catalysis, and chromatography separation. This study reports the construction and functionalization of polymer gels consisting of a polymer network of polyacrylamide derivatives with nano-sized structural units. Specifically, thermo-responsive polymer gels were synthesized by combining well-defined star-shaped polymers composed of polyacrylamide derivatives with a multifunctional initiator and linking method through a self-accelerating click reaction. The polymerization system employed a highly living approach, resulting in polymer chains characterized by narrow molecular weight distributions. The method’s high functionality facilitated the synthesis of a temperature-responsive block copolymer gel composed of N-isopropyl acrylamide (NIPA) and N-ethyl acrylamide (NEAA). The resulting polymer gel, comprising star-shaped block copolymers of NIPA and NEAA, showcases smooth volume changes with temperature jumps.

Open tubular capillary electrochromatography with dual-responsive polymer as coating for separation of chromones

Fabricating polymeric coatings that are responsive to multiple/dual stimuli is crucial and remains a major challenge in the development of highly efficient open tubular capillary electrochromatography (OT-CEC). In this study, a pH and temperature-responsive block copolymer, poly(styrene-maleic anhydride 2-dimethylamino ethyl methacrylate), P(St-MAn-DMAEMA), was designed and synthesized. Using P(St-MAn-DMAEMA) as the coating, an OT-CEC protocol was constructed for the analysis of chromones. The morphology and hydrophobicity-hydrophilicity of the polymeric coating could change via varying the environmental conditions, affecting the separation efficiency of OT-CEC. Interestingly, the best performance of OT-CEC was achieved at pH 9.7 and 45 °C via tuning the interactions between the coating and the analytes. Additionally, the proposed OT-CEC method exhibited a good linear range for the detection of the three test chromones from 10.0 to 100.0 μM, with all correlation coefficients (R2) >0.997. The coatings also had good stability and reusability. This work provides an approach for the preparation of new multiple-stimuli-responsive polymeric coatings for the establishment of OT-CEC systems.

Manipulating the Phase Transition Behavior of Dual Temperature-Responsive Block Copolymers by Adjusting Composition and Sequence

Manipulating the Phase Transition Behavior of Dual Temperature-Responsive Block Copolymers by Adjusting Composition and Sequence

In Situ and Ex Situ Studies of Ring-Like Assembly of Silica Nanoparticles in the Presence of Poly(propylene oxide)-Poly(ethylene oxide) Block Copolymers.

Block copolymer-mediated self-assembly of colloidal nanoparticles has attracted great attention for fabricating various nanoparticle arrays. We have previously shown that silica nanoparticles (SNPs) assemble into ring-like nanostructures in the presence of temperature-responsive block copolymers poly[(2-ethoxyethyl vinyl ether)-block-(2-methoxyethyl vinyl ether)] (PEOVE-PMOVE) in an aqueous phase. The ring-like nanostructures formed within an aggregate of PEOVE-PMOVE when the temperature was increased to 45 °C, at which the polymer is amphiphilic. Herein, we report that SNPs assemble into ring-like nanostructures even with a different temperature-responsive, amphiphilic block copolymer poly(propylene oxide)-block-poly(ethylene oxide) (PPO-PEO) at 45 °C. Field-emission scanning electron microscopy for SNP assemblies that were spin-coated on a substrate indicated that SNP first assembled into chain-like nanostructures and then bent into closed loops over several days. In contrast, in situ small-angle X-ray diffraction measurements revealed the formation of SNP nanorings within 75 s at 45 °C in the liquid phase. These results indicated that ring-like assembly of SNPs occurs quickly in the liquid phase, but the slow formation of Si-O-Si bonds between SNPs leads to their structure being destroyed by spin-coating. Intriguingly, SNPs with a diameter of 15 nm form a well-defined nanoring structure, with five SNPs located at the vertex points of a regular pentagon. Additionally, small-angle neutron scattering, where the contrast of the solvent (a mixture of H2O and D2O) matches that of SNPs, clarified that SNPs are contained within the spherical micelle formed from PPO-PEO. This work offers a facile and versatile approach to preparing ring-like arrays from inorganic colloidal nanoparticles, leading to applications including sensing, catalysis, and nanoelectronics.

Correction to: Synthesis and characterization of temperature-responsive block copolymers using macromonomeric initiator

Unfortunately the original article was published Online with some typos but the correct spelling is given below in the table.

Synthesis and characterization of temperature-responsive block copolymers using macromonomeric initiator

Temperature-responsive block copolymers, poly(2-(dimethyl amino)ethyl methacrylate)-b-poly(N-isopropylacrylamide) [PDMAEMA-b-PNIPAM], have been prepared by a combination of the redox polymerization and the reversible addition-fragmentation chain transfer (RAFT) polymerization. For this purpose, poly-N-isopropylacrylamide (PNIPAM-Cl) was acquired by redox polymerization of N-isopropylacrylamide (NIPAM) using 2-(2-chloroethoxy)ethanol and Ce(NH4)2(NO3)6 was used as a catalyst. Poly(DMAEMA-b-NIPAM) temperature-responsive copolymers were prepared via RAFT of 2-(dimethyl amino)ethyl methacrylate) (DMAEMA) in the presence of macromonomeric initiator (macro-CTA) which was obtained via the reaction of PNIPAM-Cl with the potassium salt of ethyl xanthogenate. The synthesized temperature-responsive block copolymer was characterized using multi-instruments and methods such as nuclear magnetic resonance spectroscopy, F(f)ourier transform infrared spectroscopy, thermogravimetric analysis, elemental analysis, differential scanning calorimetry, scanning electron microscope and UV–Vis.

Aqueous copper-mediated reversible deactivation radical polymerization (RDRP) utilizing polyetheramine derived initiators

Polyetheramines (Jeffamines™) are used in Copper-mediated reversible deactivation radical polymeriation (Cu-RDRP) in water for the synthesis of temperature-responsive block copolymers.

Temperature-responsive amperometric H2O2 biosensor using a composite film consisting of poly(N-isopropylacrylamide)-b-poly (2-acrylamidoethyl benzoate), graphene oxide and hemoglobin

A temperature-responsive biosensing film consisting of the temperature-responsive block co-polymer poly (N-isopropylacrylamide)-b-poly(2-acrylamidoethyl benzoate) (referred to as PNIPAM-b-PAAE), graphene oxide (GO), and hemoglobin (Hb) was fabricated and used to modify a glassy carbon electrode (GCE). The film provides a favorable micro-environment for Hb to facilitate the electron transfer to the GCE. Hb at PNIPAM-b-PAAE/GO/Hb (PGH) film exhibits a couple of well-defined redox peaks with a formal potential of −0.371 V (vs. SCE) and displays intrinsic electro-catalytic activity toward H2O2. The sensing film also shows temperature-tunable catalytic activity toward H2O2 that can be stimulated by temperature. Large peak currents can be seen in amperometry at 0.4 V (vs. SCE) in pH 7.0 phosphate buffer only if the temperature is above the lower critical solution temperature (LCST) of 32 °C. The response of the modified GCE is linear in the 0.1 to 3.7 μmol L−1 concentration range if operated at above 32 °C, but in the 0.2 to 3.7 μmol L−1 concentration range at below 30 °C. This behavior is attributed to the temperature-dependent phase transition of PNIPAM-b-PAAE and cooperative effect of GO. The strategy presented here in our perception meets the requirements of switchable sensors for use in bioscience and biotechnology.

Transiently Responsive Block Copolymer Micelles Based on N-(2-Hydroxypropyl)methacrylamide Engineered with Hydrolyzable Ethylcarbonate Side Chains

The lack of selectivity and low solubility of many chemotherapeutics impels the development of different biocompatible nanosized drug carriers. Amphiphilic block copolymers, composed of a hydrophilic and hydrophobic domain, show great potential because of their small size, large solubilizing power and loading capacity. In this paper, we introduce a new class of degradable temperature-responsive block copolymers based on the modification of N-(2-hydroxypropyl)methacrylamide (HPMA) with an ethyl group via a hydrolytically sensitive carbonate ester, polymerized by radical polymerization using a PEG-based macroinitiatior. The micellization and temperature-responsive behavior of the PEG-poly(HPMA-EC) block copolymer were investigated by dynamic light scattering (DLS). We observed that the polymer exhibits lower critical solution temperature (LCST) behavior and that above the cloud point (cp) of 17 °C the block copolymer self-assembles in micelles with a diameter of 40 nm. Flow cytometry analysis and confocal microscopy show a dose-dependent cellular uptake of the micelles loaded with a hydrophobic dye. The block copolymer nanoparticles were capable of delivering the hydrophobic payload into cancer cells in both 2D and 3D in vitro cultures. The block copolymer has excellent cytocompatibility, whereas loading the particles with the hydrophobic anticancer drug paclitaxel results in a dose-dependent decrease in cell viability.

Multicolor Emitting Block Copolymer-Integrated Graphene Quantum Dots for Colorimetric, Simultaneous Sensing of Temperature, pH, and Metal Ions

Highly selective optical sensors that are capable of detecting complex stimuli have attracted significant interest in environmental, biomedical, and analytical chemistry applications. In this Article, we report the development of novel and versatile platform for highly efficient, colorimetric multifunctional sensors using block copolymer-integrated graphene quantum dots (bcp-GQDs). In particular, the multisensing behavior is successfully generated simply by grafting blue-emitting, temperature-responsive block copolymers onto green-emitting, 10 nm size GQD that provides luminescent response to pH changes. Thus, the bcp-GQDs showed simultaneous, orthogonal sensing behavior to temperature and pH, as well as dose-dependent responses to different types of metal ions. In addition, the bcp-GQD sensor showed excellent reversibility and dispersion stability in pure water, indicating that our system is an ideal platform for environmental and biological applications. The detailed mechanism of the responsive behavior of the bcp-GQDs was elucidated by measurements of time-resolved fluorescence and dynamic light scattering.

Magnetic iron oxide nanoparticles grafted with poly(itaconic acid)-block-poly(N-isopropylacrylamide)

Superparamagnetic iron oxide (Fe3O4) nanoparticles were modified with a pH and temperature responsive block copolymer, poly(itaconic acid)-block-poly(N-isopropylacrylamide) (PIA-b-PNIPAM), via aqueous surface-initiated atom transfer radical polymerization (SI-ATRP). Neat and modified magnetic nanoparticles (MNPs) were characterized using Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS), and transmission electron microscopy (TEM) to discern morphology and chemical composition. Dynamic light scattering (DLS) and thermogravimetric analysis (TGA) were used to obtain the particle size distribution and phase transitions in response to temperature, and the grafting percentage, respectively. The Fe3O4–PIA-b-PNIPAM nanocomposites have a magnetic core surrounded by a ‘shell’ comprised of a block copolymer with amphiphilic stimuli-responsive blocks. The chemical composition and morphology of these MNPs modified with PIA-b-PNIPAM was confirmed, and the thermoresponsiveness of the size of these nanocomposites was demonstrated.

Control of Cell Adhesion and Detachment on Temperature-Responsive Block Copolymer Langmuir Films

ABSTRACTThis study used Langmuir-Schaefer (LS) method to produce thermo-responsive poly(N-isopropylacrylamide) (PIPAAm) modified surface. Block copolymer composed of polystyrene (PSt) and PIPAAm was synthesized by RAFT polymerization. PSt-block-PIPAAm (St-IP) with various chemical compositions was dropped on an air-water interface and formed Langmuir film by compression. Then, the Langmuir film changing a density was transferred on a hydrophobic modified glass substrate to produce St-IP transferred surface (St-IP LS surface). From the observation of atomic force microscope images, a nanostructure was observed on the transference of Langmuir films. Cell adhesion and detachment were also evaluated on the LS surfaces in response to temperature. Cell adhesion on LS surfaces at 37 °C was controlled by changing the chemical compositions and densities. After reducing temperature to 20 °C, adhering cells rapidly detached themselves with lower Am and higher composition of PIPAAm. Our method should be proved novel insights for investigating cell adhesion and detachment on thermo-responsive surfaces.

Temperature-triggered on-demand drug release enabled by hydrogen-bonded multilayers of block copolymer micelles

We report on hydrogen-bonded layer-by-layer (LbL) films as a robust, reusable platform for temperature-triggered “on-demand” release of drugs. Films with high drug loading capacity, temperature-controlled on–off drug release, and stability at physiological conditions were enabled by assembly of tannic acid (TA) with temperature-responsive block copolymer micelles (BCMs), which were pre-formed by heating solutions of a neutral diblock copolymer, poly(N-vinylpyrrolidone)-b-poly(N-isopropylacrylamide) (PVPON-b-PNIPAM), to a temperature above the lower critical solution temperature (LCST) of PNIPAM. The BCM/TA films exhibited temperature-triggered swelling/deswelling transitions at physiological conditions (swelling ratios of 1.75 and 1.2 at 37°C and 20°C, respectively). A model drug, doxorubicin (DOX) was incorporated into the film at a high drug-to-matrix ratio (~9.3wt.% of DOX per film mass), with a total loading capacity controlled by the film thickness. At 37°C, DOX was efficiently retained within the hydrophobic BCM cores of BCM/TA films, whereas exposure to a lower temperature (20°C) triggered fast DOX release. While neither bare BCM-containing films nor films loaded with DOX showed cytotoxicity at 37°C, drug released from films at lower temperature exhibited high potency against breast cancer cells. Repeated on/off drug release was demonstrated with 1.5-μm-thick DOX-loaded films, allowing at least three 30-min cooling cycles with consistent DOX (~12–16% of loaded DOX released for each cycle) released over a 4-day period. Despite significant stress associated with multiple swelling/deswelling cycles, films maintained their structural integrity in PBS, and each film could be repeatedly loaded with drug and used more than 15 times with only ~7% loss in film thickness and no obvious changes in reloading capacity or release profiles. This work presents the first proof-of-concept utility of temperature-responsive BCM-containing films for repeated on-demand release of a drug.

PH-dependent, thermosensitive polymeric nanocarriers for drug delivery to solid tumors

Polymeric micelles are promising carriers for anti-cancer agents due to their small size, ease of assembly, and versatility for functionalization. A current challenge in the use of polymeric micelles is the sensitive balance that must be achieved between stability during prolonged blood circulation and release of active drug at the tumor site. Stimuli-responsive materials provide a mechanism for triggered drug release in the acidic tumor and intracellular microenvironments. In this work, we synthesized a series of dual pH- and temperature-responsive block copolymers containing a poly(ε-caprolactone) (PCL) hydrophobic block with a poly(triethylene glycol) block that were copolymerized with an amino acid-functionalized monomer. The block copolymers formed micellar structures in aqueous solutions. An optimized polymer that was functionalized with 6-aminocaproic acid (ACA) possessed pH-sensitive phase transitions at mildly acidic pH and body temperature. Doxorubicin-loaded micelles formed from these polymers were stable at blood pH (∼7.4) and showed increased drug release at acidic pH. In addition, these micelles displayed more potent anti-cancer activity than free doxorubicin when tested in a tumor xenograft model in mice.

Thermal responsive fluorescent block copolymer for intracellular temperature sensing

In this study, a novel fluorescent and temperature responsive block copolymer has been designed and synthesized by a reversible addition–fragmentation chain transfer (RAFT) polymerization method in terms of the strategy that N-isopropylacrylamide (NIPAm), maleic anhydride (MAn) and 7-amino-4-methylcoumarin (AMC) act as the temperature responsive unit, the hydrophilic unit and the fluorescent unit, respectively. The successfully synthesized block copolymer was characterized by gel permeation chromatography (GPC) and nuclear magnetic resonance (1H NMR) spectroscopy. Meanwhile, the self-aggregation behaviour in aqueous solution and the thermo-responsive property of the block copolymer were demonstrated by particle size measurement, transmission electron microscopy (TEM) observations and lower critical solution temperature (LCST) determination, respectively. Then the variation of fluorescence intensity with temperature was confirmed. With increasing temperature, shrinking of PNIPAm chains caused the block copolymer to become more hydrophobic above the LCST, assembling larger aggregates with lower interfacial curvature. Thus a part of the fluorescent groups would be embedded inside the enlarged block copolymer micelles, resulting in lower fluorescence intensity. Furthermore, the superior hydrophilicity and biocompatibility of the block copolymer as a thermometer have been demonstrated by application in intracellular temperature sensing of MDCK cells ranging from 24 °C to 38 °C.

A modulatory bifunctional artificial enzyme with both SOD and GPx activities based on a smart star-shaped pseudo-block copolymer

An artificial smart bifunctional enzyme with both superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities was successfully constructed by the self-assembly of a porphyrin core with four suspensory adamantyl moieties and β-cyclodextrin-terminated temperature-sensitive copolymer through host–guest interaction in aqueous solution. The Mn(III) porphyrin, Mn(III)meso-tetra[1-(1-adamantyl methyl ketone)-4-pyridyl] porphyrin (MnTPyP-M-Ad), was designed as both a “supramolecular linker” and an efficient active site of SOD and the temperature-responsive block copolymer (β-CD-PEG-b-PNIPAAm-Te) with incorporated tellurium moieties in the PNIPAAm chain as GPx active sites was synthesized by ATRP. As a new type of artificial bifunctional enzymes, it exhibited stable SOD-like activity of 0.137 μM (IC50) at 37 °C, and high GPx catalytic efficiency with temperature-responsive dependence characteristic, and the new artificial enzyme was found to exhibit the highest GPx catalytic efficiency (v0 = 8.11 μM min−1) in close to physical temperature.

Folate-Conjugated Thermoresponsive Block Copolymers: Highly Efficient Conjugation and Solution Self-Assembly

A combination of controlled radical polymerization and azide-alkyne click chemistry was employed to prepare temperature-responsive block copolymer micelles conjugated with biological ligands with potential for active targeting of cancer tissues. Block copolymers of N-isopropylacrylamide (NIPAM) and N,N-dimethylacrylamide (DMA) were synthesized by reversible addition-fragmentation chain transfer (RAFT) polymerization with an azido chain transfer agent (CTA). Pseudo-first-order kinetics and linear molecular weight dependence on conversion were observed for the RAFT polymerizations. CuI-catalyzed coupling with propargyl folate resulted in folic acid residues being efficiently conjugated to the alpha-azido chain ends of the homo and block copolymers. Temperature-induced self-assembly resulted in aggregates capable of controlled release of a model hydrophobic drug. CuI-catalyzed azide-alkyne cycloaddition has proven superior to conventional methods for conjugation of biological ligands to macromolecules, and the general strategy presented herein can potentially be extended to the preparation of folate-functionalized assemblies with other stimuli susceptibility (e.g., pH) for therapeutic and imaging applications.

RAFT synthesis of poly(N‐isopropylacrylamide) and poly(methacrylic acid) homopolymers and block copolymers: Kinetics and characterization

AbstractReversible addition‐fragmentation chain transfer (RAFT) polymerization was used successfully to synthesize temperature‐responsive poly(N‐isopropylacrylamide) (PNIPAAm), poly(methacrylic acid) (PMAA), and their temperature‐responsive block copolymers. Detailed RAFT polymerization kinetics of the homopolymers was studied. PNIPAAm and PMAA homopolymerization showed living characteristics that include a linear relationship between Mn and conversion, controlled molecular weights, and relatively narrow molecular weight distribution (PDI < 1.3). Furthermore, the homopolymers can be reactivated to produce block copolymers. The RAFT agent, carboxymethyl dithiobenzoate (CMDB), proved to control molecular weight and PDI. As the RAFT agent concentration increases, molecular weight and PDI decreased. However, CMDB showed evidence of having a relatively low chain transfer constant as well as degradation during polymerization. Solution of the block copolymers in phosphate buffered saline displayed temperature reversible characteristics at a lower critical solution temperature (LCST) transition of 31°C. A 5 wt % solution of the block copolymers form thermoreversible gels by a self‐assembly mechanism above the LCST. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 102: 1191–1201, 2006