Polymerization-Induced Cooperative Assembly of Block Copolymer and Homopolymer via RAFT Dispersion Polymerization

Polymerization-induced cooperative assembly (PICA) is developed to promote morphological transitions at high solids via RAFT dispersion polymerization, using both a macromolecular chain transfer agent (macro-CTA) and a small molecule chain transfer agent (CTA) to generate nano-objects consisting of well-defined block copolymer and homopolymer. PICA is demonstrated to promote morphological transitions under various conditions. Elemental mapping provides unambiguous evidence for the uniform distribution of the homopolymer within the core of the nano-objects. It is proposed that the growing homopolymer first reaches its solubility limit and forms aggregates, which induce the adsorption of the growing block copolymer. This effective and robust PICA approach significantly expands the capability to promote morphological transitions in RAFT dispersion polymerization and will facilitate the efficient synthesis of various higher-order morphologies at high solids

Photocontrolled RAFT Polymerization Mediated by a Supramolecular Catalyst

A photocontrolled reversible addition–fragmentation chain transfer (RAFT) polymerization mediated by a supramolecular photoredox catalyst is reported. Cucurbit[7]­uril (CB[7]) was used to form a host–guest complex with Zn­(II) meso-tetra­(4-naphthalylmethylpyridyl) porphyrin (ZnTPOR) to prevent aggregation of ZnTPOR, which in combination with a chain transfer agent (CTA) initiated efficient and controlled RAFT polymerization in water under visible light. RAFT polymerization was significantly affected by the subtle interplay of host–guest, electrostatic, and steric interactions among CB[7], ZnTPOR, and CTA. Polymerization rate was remarkably improved using CB[7]@ZnTPOR in comparison with that using ZnTPOR. The use of supramolecular interactions to modulate photocontrolled RAFT polymerization provides new opportunities to manipulate controlled radical polymerizations

In Situ Cross-Linking as a Platform for the Synthesis of Triblock Copolymer Vesicles with Diverse Surface Chemistry and Enhanced Stability via RAFT Dispersion Polymerization

An intrinsic dilemma exists for block copolymer vesiclesimproving the colloidal stability of vesicles using long/charged stabilizing blocks lowers the propensity of morphological transition to vesicles. Moreover, maintaining the vesicular morphology requires effective structure stabilization via cross-linking. We report a strategy to circumvent this problem and simultaneously improve the colloidal and structural stability of vesicles synthesized via polymerization-induced self-assembly (PISA) using dispersion polymerization. More specifically, in situ cross-linked poly­(<i>N</i>,<i>N</i>-dimethyl­acrylamide)-<i>b</i>-poly­(diacetone acrylamide-<i>co</i>-allylacrylamide) diblock copolymer vesicles are first synthesized via aqueous dispersion polymerization, which then serve as a robust platform to initiate the growth of a third hydrophilic block of either neutral poly­(<i>N</i>,<i>N</i>-dimethyl­acrylamide), anionic poly­(2-acrylamido-2-methyl-1-propane­sulfonic acid sodium salt), or cationic poly­(3-acrylamido­propyl trimethyl­ammonium chloride) with retained vesicular morphology. The formed cross-linked triblock copolymer vesicles have advantages of diverse surface chemistry and arbitrary stabilizing block length. As a control experiment, synthesis from linear diblock copolymer vesicles provides a mixture of triblock copolymer vesicles and spheres. The successful synthesis of triblock copolymer vesicles with a binary mixture of two hydrophilic stabilizing blocks is supported by dynamic light scattering (DLS), transmission electron microscopy (TEM), electrophoresis, and X-ray photoelectron spectroscopy (XPS). Both linear and cross-linked triblock copolymer vesicles are subjected to solvent dissolution, freeze-drying, and surfactant challenge studies, which collectively demonstrate that cross-linked triblock copolymers can maintain their vesicular structure and show excellent colloidal and structural stability, as indicated by DLS, TEM, and transmittance measurements

Artificial Peroxidase/Oxidase Multiple Enzyme System Based on Supramolecular Hydrogel and Its Application as a Biocatalyst for Cascade Reactions

Inspired by delicate structures and multiple functions of natural multiple enzyme architectures such as peroxisomes, we constructed an artificial multiple enzyme system by coencapsulation of glucose oxidases (GOx) and artificial peroxidases in a supramolecular hydrogel. The artificial peroxidase was a functional complex micelle, which was prepared by the self-assembly of diblock copolymer and hemin. Compared with catalase or horseradish peroxidase (HRP), the functional micelle exhibited comparable activity and better stability, which provided more advantages in constructing a multienzyme with a proper oxidase. The hydrogel containing the two catalytic centers was further used as a catalyst for green oxidation of glucose, which was a typical cascade reaction. Glucose was oxidized by oxygen (O₂) via the GOx-mediated reaction, producing toxic intermediate hydrogen peroxide (H₂O₂). The produced H₂O₂ further oxidized peroxidase substrates catalyzed by hemin-micelles. By regulating the diffusion modes of the enzymes and substrates, the artificial multienzyme based on hydrogel could successfully activate the cascade reaction, which the soluble enzyme mixture could not achieve. The hydrogel, just like a protective covering, protected oxidases and micelles from inactivation via toxic intermediates and environmental changes. The artificial multienzyme could efficiently achieve the oxidation task along with effectively eliminating the toxic intermediates. In this way, this system possesses great potentials for glucose detection and green oxidation of a series of substrates related to biological processes

RAFT Polymerization-Induced Self-Assembly as a Strategy for Versatile Synthesis of Semifluorinated Liquid-Crystalline Block Copolymer Nanoobjects

Polymerization-induced self-assembly is demonstrated as a powerful platform for the synthesis of block copolymers comprising a semifluorinated liquid-crystalline block. This strategy transforms the deficiency of polymer insolubility encountered in traditional homogeneous solution protocols to the strength for dispersion polymerization, thus, enabling direct access to polymorphic block copolymer nanoobjects at high concentrations and with quantitative conversions. The versatility of this strategy is highlighted by polymerizations in a wide selection of inexpensive solvents, from nonpolar to highly polar, to afford various block copolymers with distinct combinations of amorphous/crystalline or hydrophilic/hydrophobic/fluorinated segments. The utility of the nanoparticles is demonstrated as robust Pickering emulsifiers for commonly considered good solvents

Formation of Multidomain Hydrogels via Thermally Induced Assembly of PISA-Generated Triblock Terpolymer Nanogels

Polymerization-induced self-assembly (PISA) is a rapidly evolving method for the efficient preparation of well-defined nano-objects. PISA-generated nano-objects have been explored in this work for the responsive formation of multidomain hydrogels by thermally induced assembly of doubly thermoresponsive triblock terpolymer nanogels. The nanogels consist of a thermoresponsive poly­(diethylene glycol ethyl acrylate) (PDEGA) outer block with a lower thermal transition temperature, a hydrophilic poly­(<i>N</i>,<i>N</i>-dimethyl­acrylamide) (PDMA) midblock, and a <i>N</i>,<i>N</i>′-methylene­bis­(acrylamide) (BIS) cross-linked, thermoresponsive poly­(<i>N</i>-isopropyl­acrylamide) (PNIPAM) core block with a higher thermal transition temperature. The unique location of these two thermoresponsive blocks of differing transition temperatures in the PDEGA–PDMA–P­(NIPAM-<i>co</i>-BIS) nanogels is rationally designed to facilitate room-temperature gelation and is synthetically realized via judicious selection of water–ethanol mixtures under dispersion polymerization conditions. The nanogels were characterized by turbidimetry, dynamic light scattering (DLS), and transmission electron microscopy (TEM). Gelation behavior of the nanogels was investigated by the inverted vial method as well as dynamic rheology sweeps. In comparison with PNIPAM–PDMA–P­(DEGA-<i>co</i>-BIS) nanogel and a triblock terpolymer of similar composition, the PDEGA–PDMA–P­(NIPAM-<i>co</i>-BIS) nanogels exhibit a good combination of gelation sensitivity and gel strength. The gelation ability, sensitivity, and mechanical properties are affected by the block ratios as well as the cross-linking density in the core of the nanogels

Hemin-Block Copolymer Micelle as an Artificial Peroxidase and Its Applications in Chromogenic Detection and Biocatalysis

Following an inspiration from the fine structure of natural peroxidases, such as horseradish peroxidase (HRP), an artificial peroxidase was constructed through the self-assembly of diblock copolymers and hemin, which formed a functional micelle with peroxidase-like activity. The pyridine moiety in block copolymer poly­(ethylene glycol)-<i>block</i>-poly­(4-vinylpyridine) (PEG-<i>b</i>-P4VP) can coordinate with hemin, and thus hemin is present in a five-coordinate complex with an open site for binding substrates, which mimics the microenvironment of heme in natural peroxidases. The amphiphilic core–shell structure of the micelle and the coordination interaction of the polymer to the hemin inhibit the formation of hemin μ-oxo dimers, and thereby enhance the stability of hemin in the water phase. Hemin-micelles exhibited excellent catalytic performance in the oxidation of phenolic and azo compounds by H₂O₂. In comparison with natural peroxidases, hemin-micelles have higher catalytic activity and better stability over wide temperature and pH ranges. Hemin-micelles can be used as a detection system for H₂O₂ with chromogenic substrates, and they anticipate the possibility of constructing new biocatalysts tailored to specific functions

Multifunctional Polymer Vesicles for Synergistic Antibiotic–Antioxidant Treatment of Bacterial Keratitis

As an acute ophthalmic infection, bacterial keratitis (BK) can lead to severe visual morbidity, such as corneal perforation, intraocular infection, and permanent corneal opacity, if rapid and effective treatments are not available. In addition to eradicating pathogenic bacteria, protecting corneal tissue from oxidative damage and promoting wound healing by relieving inflammation are equally critical for the efficient treatment of BK. Besides, it is very necessary to improve the bioavailability of drugs by enhancing the ocular surface adhesion and corneal permeability. In this investigation, therefore, a synergistic antibiotic–antioxidant treatment of BK was achieved based on multifunctional block copolymer vesicles, within which ciprofloxacin (CIP) was simultaneously encapsulated during the self-assembly. Due to the phenylboronic acid residues in the corona layer, these vesicles exhibited enhanced muco-adhesion, deep corneal epithelial penetration, and bacteria-targeting, which facilitated the drug delivery to corneal bacterial infection sites. Additionally, the abundant thioether moieties in the hydrophobic membrane enabled the vesicles to both have ROS-scavenging capacity and accelerated CIP release at the inflammatory corneal tissue. In vivo experiments on a mice model demonstrated that the multifunctional polymer vesicles achieved efficient treatment of BK, owing to the enhanced corneal adhesion and penetration, bacteria targeting, ROS-triggered CIP release, and the combined antioxidant–antibiotic therapy. This synergistic strategy holds great potential in the treatment of BK and other diseases associated with bacterial infections

Effect of the Surface Charge of Artificial Chaperones on the Refolding of Thermally Denatured Lysozymes

Artificial chaperones are of great interest in fighting protein misfolding and aggregation for the protection of protein bioactivity. A comprehensive understanding of the interaction between artificial chaperones and proteins is critical for the effective utilization of these materials in biomedicine. In this work, we fabricated three kinds of artificial chaperones with different surface charges based on mixed-shell polymeric micelles (MSPMs), and investigated their protective effect for lysozymes under thermal stress. It was found that MSPMs with different surface charges showed distinct chaperone-like behavior, and the neutral MSPM with PEG shell and PMEO₂MA hydrophobic domain at high temperature is superior to the negatively and positively charged one, because of the excessive electrostatic interactions between the protein and charged MSPMs. The results may benefit to optimize this kind of artificial chaperone with enhanced properties and expand their application in the future

CHOP-eNOS pathway in baicalin mediated protective role.

<p>Cardiomyocytes were transfected with or without siRNA for 24(BC, 25 µM) and L-NAME (10 µM) pretreatment. Viability was measured by the MTT-assay in cardiomyocytes (A, D, G). Apoptosis was tested by TUNEL analysis (B, E, H). Quantitative analysis of TUNEL-positive cardiomyocytes (C, F, I). A, B, C: *P<0.05 vs Tm+si NC, n = 5; D, E, F: *P<0.05 vs Ctrl+Tm, **P<0.05 vs Ctrl+Tm+BC, n = 5; G, H, I: *P<0.05 vs Tm+si CHOP, **P<0.05 vs Tm+BC+si CHOP, n = 5.</p