Dual Gas-responsive Fluorescent Diblock Copolymer Synthesized via RAFT Polymerization.

Stimulus-responsive polymers with luminescence properties have a wide range of applications in the fields of controlled drug release, fluorescent probes, and biological stents. In this paper, carbon dioxide (CO2)/oxygen (O2) dual-responsive fluorescent diblock copolymers were synthesized by the reversible addition-fragmentation chain transfer (RAFT) polymerization method with two fluorescent monomers synthesized as its luminescence source, DEAEMA (CO2 responsive monomer) and tFMA (O2 responsive monomer). An experimental study demonstrated that the synthesized stimulus-responsive fluorescent polymer had a high sensitivity to CO2; the double-responsive fluorescent diblock copolymer could form and achieve the reversal of polymer micelles in the aqueous solution when it was sequentially subjected to the introduction of CO2 and O2.

Polymeric Drug Delivery System Based on Pluronics for Cancer Treatment.

Pluronic polymers (pluronics) are a unique class of synthetic triblock copolymers containing hydrophobic polypropylene oxide (PPO) and hydrophilic polyethylene oxide (PEO) arranged in the PEO-PPO-PEO manner. Due to their excellent biocompatibility and amphiphilic properties, pluronics are an ideal and promising biological material, which is widely used in drug delivery, disease diagnosis, and treatment, among other applications. Through self-assembly or in combination with other materials, pluronics can form nano carriers with different morphologies, representing a kind of multifunctional pharmaceutical excipients. In recent years, the utilization of pluronic-based multi-functional drug carriers in tumor treatment has become widespread, and various responsive drug carriers are designed according to the characteristics of the tumor microenvironment, resulting in major progress in tumor therapy. This review introduces the specific role of pluronic-based polymer drug delivery systems in tumor therapy, focusing on their physical and chemical properties as well as the design aspects of pluronic polymers. Finally, using newer literature reports, this review provides insights into the future potential and challenges posed by different pluronic-based polymer drug delivery systems in tumor therapy.

Electrochemical dopamine sensor based on the use of a thermosensitive polymer and an nanocomposite prepared from multiwalled carbon nanotubes and graphene oxide.

An electrochemical dopamine sensor with a temperature-controlled switch was constructed by using a mixture of thermo-sensitive block copolymers (type tBA-PDEA-tBA), graphene oxide (GO) and multi-walled carbon nanotubes (MWCNTs). If the temperature is below 26 °C, the polymer on the glassy carbon electrode (GCE) is stretched, the distance between the MWCNTs is large, and the charge transfer resistance (Rct) of the composite also is large. In the presence of dopamine, the electron transfer at the electrode is strongly retarded and in the "off" state. At above 38 °C, the polymer is shrunk and the Rct is much smaller. The presence of dopamine results in a rapid electron transfer at the GCE, and this is referred to as the "on" state. At temperatures between 26 and 38 °C, the polymer shrinks slightly and has a "spring-like" state. There is a linear relationship between the response current (typically measured at a potential as low as 0.16 V vs. Ag/AgCl) and temperature. The response to dopamine is linear in the 0.06 to 4.2 µM and 4.2 to 18.2 µM concentration range, and the detection limit is 42 nM. Conceivably, this approach provides a novel approach towards the design of electrochemical sensors based on the use of thermo-sensitive polymers. Graphical abstract Schematic presentation of reversible and temperature-controlled electrochemical response of dopamine on the thermo-sensitive block copolymers (tBA-PDEA-tBA) / multi-walled carbon nanotubes (MWCNTs) / graphene oxide (GO) / glassy carbon electrode (GCE).

Dual Stimulus-Responsive Enzyme@Metal-Organic Framework-Polymer Composites toward Enhanced Catalytic Performance for Visual Detection of Glucose.

Enzyme immobilization on a metal-organic framework (enzyme@MOF) has been proven to be a promising strategy for boosting catalysis and biosensing applications. However, promoting the catalytic performance of polymer-modified enzyme@MOF composites remains an ongoing challenge. Herein, a protocol for enzyme immobilization was designed by using a smart polymer-modified MOF (UiO-66-NH2, UN) as the support. Through in situ polymerization, the dual stimulus-responsive poly(N-2-dimethylamino ethyl methacrylate) (PDM) was prepared. The PDM as a "soft cage" protected the immobilized glucose oxidase (GOx)-horseradish peroxidase (HRP) on the surface of the rigid UN. The confinement effect was generated by varying the temperature and pH, thereby improving the catalytic activity of the GOx-HRP@UN-PDM composites. In comparison with free enzymes, the fabricated composites exhibited an 8.9-fold enhancement in catalytic performance (Vmax) at pH 5.0 and 49 °C. Furthermore, relying on a cascade reaction generated in the composites, an assay was developed for the visual detection of glucose in rat serum. This study introduces a groundbreaking approach for the construction of smart enzyme@MOF-polymer composites with high catalytic activity for sensitive monitoring of biomolecules.

Development of a novel and efficient cell culture flocculation process using a stimulus responsive polymer to streamline antibody purification processes.

Recent advances in mammalian cell culture processes have significantly increased product titers, but have also resulted in substantial increases in cell density and cellular debris as well as process and product related impurities. As such, with improvements in titer, corresponding improvements in downstream processing are essential. In this study we have developed an alternative antibody harvest process that incorporates flocculation using a novel stimulus responsive polymer, benzylated poly(allylamine), followed by depth filtration. As tested on multiple antibodies, this process demonstrates high process yield, improved clearance of cells and cell debris, and efficient reduction of aggregates, host cell proteins (HCP) and DNA. A wide operating window was established for this novel flocculation process through design of experiments condition screening and optimization. Residual levels of impurities in the Protein A eluate were achieved that potentially meet requirements of drug substance and thus alleviate the burden for further impurities removal in subsequent chromatography steps. In addition, efficient clearance of residual polymer was demonstrated using a fluorescence tagged polymer in the presence of a stimulus reagent. The mechanism of HCP and aggregates removal during flocculation was also explored. This novel and efficient process can be easily integrated into current mAb purification platforms, and may overcome downstream processing challenges.

Cinnamaldehyde-based poly(thioacetal): A ROS-awakened self-amplifying degradable polymer for enhanced cancer immunotherapy.

Although stimuli-responsive polymers have emerged as promising strategies for intelligent cancer therapy, limited polymer degradation and insufficient drug release remain a challenge. Here, we report a novel reactive oxygen species (ROS)-awakened self-amplifying degradable cinnamaldehyde (CA)-based poly(thioacetal) polymer. The polymer consists of ROS responsive thioacetal (TA) group and CA as the ROS generation agent. The self-amplified polymer degradation process is triggered by endogenous ROS-induced cleavage of the TA group to release CA. The CA released then promotes the generation of more ROS through mitochondrial dysfunction, resulting in amplified polymer degradation. More importantly, poly(thioacetal) itself can trigger immunogenic cell death (ICD) of the tumor cells and its side chains can be conjugated with indoleamine 2,3-dioxygenase 1 (IDO-1) inhibitor to reverse the immunosuppressive tumor microenvironment for synergistic cancer immunotherapy. The self-amplified degradable poly(thioacetal) developed in this work provides insights into the development of novel stimulus-responsive polymers for enhanced cancer immunotherapy.

Application of the water-insoluble, temperature-responsive block polymer poly(butyl methacrylate-block-N-isopropylacrylamide) for pluripotent stem cell culture and cell-selective detachment.

Induced pluripotent stem (iPS) cells have been widely studied in regenerative medicine, pathology modeling, and drug screening. Stable mass culture of iPS cells is essential for these applications. iPS cells can spontaneously differentiate into other cells during culture, and removal of these differentiated cells is necessary. Herein, a cost-effective culture method suitable for mass culture and a detailed analysis of the selective detachment of iPS cells are presented. A simple method for coating the water-insoluble thermoresponsive polymer poly (butyl methacrylate-block-N-isopropylacrylamide) on commercially available polystyrene dishes was employed. Analysis of the effects of the polymer composition, coating thickness, and surface structure on iPS cell culture/detachment showed that a coating thickness of approximately 10-40 nm using a polymer with a high poly (N-isopropylacrylamide) content was suitable for iPS cell detachment. Moreover, an interesting change in surface morphology was observed following temperature variation, thereby affecting laminin adsorption. Second, selective detachment in cocultures of iPS cells and differentiated cells enabled collection of iPS cells with more than 98% purity. Finally, long-term iPS cell culture was conducted using temperature-responsive cell detachment. Overall, long-term maintenance-free culture of iPS cells was possible without manual removal of differentiated cells.

Therapeutic-Ultrasound-Triggered Shape Memory of a Melamine-Enhanced Poly(vinyl alcohol) Physical Hydrogel.

Therapeutic-ultrasound-triggered shape memory was demonstrated for the first time with a melamine-enhanced poly(vinyl alcohol) (PVA) physical hydrogel. The addition of a small amount of melamine (up to 1.5 wt %) in PVA results in a strong hydrogel due to the multiple H-bonding between the two constituents. A temporary shape of the hydrogel can be obtained by deformation of the hydrogel (∼65 wt % water) at room temperature, followed by fixation of the deformation by freezing/thawing the hydrogel under strain, which induces crystallization of PVA. We show that the ultrasound delivered by a commercially available device designed for the patient's pain relief could trigger the shape recovery process as a result of ultrasound-induced local heating in the hydrogel that melts the crystallized PVA cross-linking. This hydrogel is thus interesting for potential applications because it combines many desirable properties, being mechanically strong, biocompatible, and self-healable and displaying the shape memory capability triggered by a physiological stimulus.