Temperature-sensitive Block Copolymer Research Articles

Temperature and molecular structure-dependent self-assembly of PS-b-PEO at the liquid/liquid interface

It is of great importance to explore the self-assembly behavior of amphiphilic block copolymers at the liquid/liquid interface for the construction of hierarchical nanostructures and evaluation of emulsifiers. In this work, the adsorption and self-assembly of PS-b-PEO, a typical amphiphilic and temperature-sensitive block copolymer with abundant coordination sites were investigated by using a liquid/liquid interfacial assembly method in which pure water covered a chloroform solution of PS-b-PEO to form a planar liquid/liquid interface first, and then the aqueous solution of copper acetate was added dropwise into the water. It was found that spontaneous interfacial emulsification occurred when Cu2+ aqueous solution was added into the water at 28 °C. The PS-b-PEOs with shorter PEO chains self-assembled into hollow spheres, hierarchical hollow spheres, and hollow spheres with layered walls, depending on the relative length of the PEO blocks; while the PS-b-PEO with a longer PEO chain formed Janus sheets. While, PS-b-PEOs self-assembled into Janus sheets with monolayer or stepped multilayer structures at 18 and 8 °C through interfacial adsorption and assembly, regulated by the molecular structures. In addition, the concentrations of PS-b-PEO and Cu2+ ions also affect the self-assembly behavior and the aggregate morphologies.

Biodegradable Block Copolymer-Tannic Acid Glue.

Bioadhesives are becoming an essential and important ingredient in medical science. Despite numerous reports, developing adhesive materials that combine strong adhesion, biocompatibility, and biodegradation remains a challenging task. Here, we present a biocompatible yet biodegradable block copolymer-based waterborne superglue that leads to an application of follicle-free hair transplantation. Our design strategy bridges self-assembled, temperature-sensitive block copolymer nanostructures with tannic acid as a sticky and biodegradable polyphenolic compound. The formulation further uniquely offers step-by-step increases in adhesion strength via heating–cooling cycles. Combining the modular design with the thermal treating process enhances the mechanical properties up to 5 orders of magnitude compared to the homopolymer formulation. This study opens a new direction in bioadhesive formulation strategies utilizing block copolymer nanotechnology for systematic and synergistic control of the material’s properties.

A Smart Drug Delivery System Based on Thermo-Responsive Polymer Gated Au NRs@SiO2 Nano-Platform

A key challenge for nanoparticles-based drug delivery system is to achieve manageable drug release in tumour cell. In this study, a versatile system combining photothermal therapy and controllable drug release for tumour cells using temperature-sensitive block copolymer coupled Au NRs@SiO2 is reported. While the Au NRs serve as hyperthermal agent and the mesoporous silica was used to improve the drug loading and decrease biotoxicity. The block copolymer acted as “gatekeeper” to regulate the release of model drug (Doxorubicin hydrochloride, DOX). Through in vivo and in vitro experiments, we achieved the truly controllable drug release and photothermal therapy with the collaborative effect of the three constituents of the nanocomposites. The reported nanocomposites pave the way to high-performance controllable drug release and photothermal therapy system.

Controllable length adjustment of polyaniline particle with temperature sensitive block copolymer as template

Although the diameter of conductive polymer nanoparticles can be controlled effectively, the uniformity of particle length is still very challenging. In this study, with the temperature‐sensitive block copolymer PS111‐b‐PNIPAM114 as the template, the morphology and size of polyaniline (PANI) particles had been controllably adjusted through the change of temperature. Additionally, the electrochemical performance of each sample was investigated. After PS111‐b‐PNIPAM114 was synthesized through the reversible addition‐fragmentation chain transfer radical polymerization (RAFT), with its vesicular micelle as the “template”, the PANI particles with uniform length distribution were prepared successfully at 40°C. The average length of PANI particles after template removal was 254.07 nm with a short tail distribution, which was closer to the average than the standard normal distribution. Electrochemical results of PANI showed that it had good electrochemical activity with fast charge and discharge ability. And, with the current density of 1 A·g−1, its discharge‐specific capacitance could reach up to 805.61 F·g−1.

Azlactone-functionalized smart block copolymers for organocatalyst immobilization

Nucleophilic ring-opening reaction of azlactone moieties was used for the immobilization of organocatalysts on smart block copolymers. Copolymerization of N-isopropylacrylamide with 2-vinyl-4,4-dimethylazlactone using a PEG-based macro-RAFT agent afforded temperature-sensitive block copolymers bearing azlactone side groups. Three different organocatalysts possessing primary amino groups were synthesized on the basis of L-proline and L-prolineamide using standard peptide coupling procedures. Organocatalyst immobilization was achieved using a post-polymerization reaction of the primary amino group with the azlactone moiety. The organocatalyst-functionalized block copolymers exhibited a temperature induced self-aggregation upon exceeding a critical phase transition temperature. The block copolymer aggregates with the immobilized organocatalyst in the core were subjected to the aldol reaction of cyclohexanone and p-nitrobenzaldehyde in water. Good diastereo- and enantioselectivities were observed, particularly for the immobilized prolineamides. Organocatalyst separation and reusability was demonstrated for five reaction cycles with no loss in catalyst reactivity. Finally, the applicability of the immobilized organocatalyst to the aldol reaction of cyclohexanone with differently substituted benzaldehydes in water was shown.

Development of an Injectable Tissue Adhesive Hybrid Hydrogel for Growth Factor-Free Tissue Integration in Advanced Wound Regeneration

The development of injectable hydrogels with tunable multifunctional properties, for example, adhesive, elastic, swelling, biodegradable, and wound-healing properties that mimic the dynamic-healing process of skin regeneration, is currently a major challenge in tissue regeneration. Here, we report a fillable topical formulation of injectable gelatins (IGs) for the integration of advanced excisional wounds. Bioresorbable temperature-sensitive block copolymer was conjugated to the backbone of gelatins to form a dynamic coordinative network of IGs. The flexible IG precursors transformed to viscoelastic hydrogel at the subcutaneous tissues with cell affinity and tissue adhesive properties. The microporous dynamic network of IGs allows access to nutrients and recruits immune cells that accelerate neovascularization within a hydrogel network. Combined with adhesive and neovascularization properties, the IGs alone exhibit accelerated wound healing in open wounds featured by skin appendages without scar formation. More remarkably, in an excisional wound (1 cm × 1 cm) animal model, the IGs promoted the wound healing as observed by the skin appendages. Furthermore, histological analysis demonstrated that IGs not only accelerate the rate of wound healing but also promoted the quality of wound healing observed by collagen deposition and neovascularization. The in situ forming IGs with a superior adhesive property can be considered as promising wound dressing materials for the treatment of multiple wounds, without the need for the encapsulation of biofactors or antibacterial metals. The IGs prepared in this study can also be employed to repair tissues or organs using minimal invasive administration.

Construction of a smart glutathione peroxidase mimic with temperature responsive activity based on block copolymer

To construct a smart artificial antioxidative enzyme on a nano-scaffold, a novel method for designing glutathione peroxidase (GPx) active sites on block copolymer vesicles was developed by simple blending predesigned temperature-sensitive block copolymers with the main catalytic units of GPx. A series of functional block copolymers, poly(N-isopropylacrylamide)-b-polyacrylamides loaded with recognition and catalytic sites, were synthesized viaATRP and click chemistry. Through altering the molar ratio of the functional copolymers, the optimum GPx mimic based on copolymer vesicles was obtained by self-assembly of temperature-sensitive block copolymers through a blending process. Significantly, the catalytic activity of the optimum GPx mimic can be well modulated by changing the temperature. It was proved that the change in self-assembly structure of the block copolymer played an important role in the modulation of the catalytic activity. This method not only bodes well for designing smart antioxidative enzyme mimics that could be used in cosmetics as antioxidative additives but also highlights the construction of other regulatory biologically related functional biomaterials.

Construction of Smart Glutathione Peroxidase Mimic Based on Hydrophilic Block Copolymer with Temperature Responsive Activity

A temperature-sensitive block copolymer (PAAm-b-PNIPAAm-Te) with a glutathione peroxidase-like active site was synthesized via ATRP. As a new glutathione peroxidase (GPx) mimic, it displays typical saturation kinetic behaviors and high catalytic activity. More importantly, the catalytic activity of the polymer can be well modulated by changing the temperature. The experiments proved that a change in the self-assembly structure of the polymer plays a key role for the modulation of catalytic activity. As a contrast, another block copolymer, PAAm-Te-b-PNIPAAm, was synthesized. In comparison with PAAm-b-PNIPAAm-Te, the different temperature dependent catalytic behavior seen further indicates that the micellar structure plays an important role in modulating the catalytic activity of the smart enzyme model.

Sulfonamide-Based pH- and Temperature-Sensitive Biodegradable Block Copolymer Hydrogels

Novel pH- and temperature-sensitive biodegradable poly(epsilon-caprolactone-co-lactide)-poly(ethylene glycol) (PCLA-PEG) block copolymers were synthesized with oligomeric sulfamethazine (OSM) end groups (OSM-PCLA-PEG-PCLA-OSM). Aqueous solutions of these block copolymers have shown sol-gel transition behavior upon both temperature and pH changes under physiological conditions (37 degrees C, pH 7.4). The sol-gel transition of these block copolymer solutions was fine-tuned by controlling the PEG length, the hydrophobic to hydrophilic block ratio (PCLA/PEG), and the molecular weight of the sulfamethazine oligomer. Since changes in temperature do not induce gel formation in this pH- and temperature-sensitive block copolymer solution, this hydrogel can be employed as an injectable carrier using a long guide catheter into the body. In addition, the pH of the block copolymer solution showed no change following PCLA degradation over 1 month, and no indication of gel collapse was observed on addition of buffer solution. As such, these properties make the OSM-PCLA-PEG-PCLA-OSM hydrogel an ideal candidate for use as an injectable carrier for certain protein-based drugs known to denature in low-pH environments.

Genetic synthesis and characterization of pH- and temperature-sensitive silk-elastinlike protein block copolymers.

The purpose of this work was to synthesize and characterize a pH- and temperature-sensitive block copolymer containing repeating sequences from silk (Gly-Ala-Gly-Ala-Gly-Ser) and elastin (Gly-Val-Gly-Val-Pro) protein. The monomer contained one repeat of silk and eight repeat units of elastin, with the first valine in one of the elastin repeats being replaced by glutamic acid. The copolymer was synthesized using genetic engineering techniques. The sensitivity of the copolymer to pH and temperature was examined at various polymer concentrations and ionic strengths. Turbidity measurements were carried out over a temperature range of 20 to 100 degrees C at various pH, concentration, and ionic strength values. The introduction of an ionizable residue (glutamic acid) rendered the copolymer sensitive to changes in pH. The transition termperature (T(t)), the temperature at which the polymer became insoluble upon increase in temperature, was modulated by changing the pH. In general, the T(t) value, was found: (1) to increase with an increase in pH, (2) to decrease with increasing ionic strength, and (3) to decrease with increasing concentration. Results of these studies suggest that by strategic placement of charged amino acids in genetically engineered silk-elastinlike protein block copolymers it is possible to precisely control sensitivity to stimuli such as pH and temperature.