Glycol Methyl Ether Methacrylate Research Articles

Toward understanding polymeric micelle stability regulated by diverse physico-chemical strategies and their stabilized mechanism

Despite polymeric micelles as a kind of promising drug delivery system (DDS), their unsatisfactory stability in physiological environment remains a barrier to clinical translation. Thus, the present study aims at understanding the factors and underlying mechanism to stabilize micelles. Accordingly, we designed triblock copolymers poly(2-phenoxyethyl methacrylate)-b-poly(2-oxopropyl methacrylate)-b-poly[poly(ethylene glycol) methyl ether methacrylate] (PPOEMA-b-POPMA-b-PPEGMA), and prepared cross-linked polymeric micelles (CPM) self-assembled by these copolymers. Förster resonance energy transfer (FRET) fluorescence test showed cross-linked structure was more stable in diluted environment. Meanwhile, cross-linking and higher proportion of hydrophilic shell retarded the dissociation of micelles after incubating with protein. Experiment and simulation results revealed stabilized mechanism of micelles regulated by different strategies. Firstly, Van der Waals interaction between benzene rings would be the driving force of micelle stability. Secondly, cross-linking reshaped micelle structure, thereby evoking π-π stacking effect and simultaneously limiting movement of polymer segments, resulting in the more rigid micelle structure. Then, longer hydrophilic branch chain led to better coverage of hydrophilic shell, conducive to micelle stability in thermodynamics. In addition, doxorubicin (DOX)-loaded micelles possessed pH-responsive property and remarkably inhibited the growth of tumor cells. These findings are of significance in further understanding of polymeric micelle stability, and provide new insight for the design of stable and long-circulating materials for drug delivery.

The Nanostructured Self-Assembly and Thermoresponsiveness in Water of Amphiphilic Copolymers Carrying Oligoethylene Glycol and Polysiloxane Side Chains.

Amphiphilic copolymer self-assembly is a straightforward approach to obtain responsive micelles, nanoparticles, and vesicles that are particularly attractive for biomedicine, i.e., for the delivery of functional molecules. Here, amphiphilic copolymers of hydrophobic polysiloxane methacrylate and hydrophilic oligo (ethylene glycol) methyl ether methacrylate with different lengths of oxyethylenic side chains were synthesized via controlled RAFT radical polymerization and characterized both thermally and in solution. In particular, the thermoresponsive and self-assembling behavior of the water-soluble copolymers in water was investigated via complementary techniques such as light transmittance, dynamic light scattering (DLS), and small-angle X-ray scattering (SAXS) measurements. All the copolymers synthesized were thermoresponsive, displaying a cloud point temperature (Tcp) strongly dependent on macromolecular parameters such as the length of the oligo(ethylene glycol) side chains and the content of the SiMA counits, as well as the concentration of the copolymer in water, which is consistent with a lower critical solution temperature (LCST)-type behavior. SAXS analysis revealed that the copolymers formed nanostructures in water below Tcp, whose dimension and shape depended on the content of the hydrophobic components in the copolymer. The hydrodynamic diameter (Dh) determined by DLS increased with the amount of SiMA and the associated morphology at higher SiMA contents was found to be pearl-necklace-micelle-like, composed of connected hydrophobic cores. These novel amphiphilic copolymers were able to modulate thermoresponsiveness in water in a wide range of temperatures, including the physiological temperature, as well as the dimension and shape of their nanostructured assemblies, simply by varying their chemical composition and the length of the hydrophilic side chains.

Self-healing polymer electrolytes with dynamic-covalent borate for solid-state lithium metal batteries

Developing a solid polymer electrolyte (SPE) combining superior interface stability with high ionic conductivity is still a challenge in the energy storage field. Herein, a series of novel self-healing solid polymer electrolytes were prepared by free radical photopolymerization with poly(ethylene glycol) methyl ether methacrylate and monomers containing borate. The reversible reaction induced by interesterification of borate ester endows the polymer electrolytes with excellent self-healing ability. The comb-like structure based on flexible poly(ethylene glycol) provides an amorphous state, which is conducive to lithium-ion transport. Further benefiting from the strong interaction between electron capture groups and anions of electrolyte salts, the borate-containing comb-shaped solid polymer electrolytes (PPBSPE) films display optimal ionic conductivity of 0.272 mS cm−1 at 60 °C, satisfactory transfer number for lithium ion, wide working voltage window, and remarkable stability towards lithium metal. The initial discharge capacities of the cell based on PPBSPE reach 156.2 mAh g−1 at a current rate of 0.1C, and high Coulombic efficiency (CE) of 99.4 %. This enhancement is due to the introduction of borate to the comb-shaped polymer, which is beneficial to form a more suitable electrolyte that can stabilize and improve the performance of lithium metal batteries.

Exploring the Effect of Drug Loading on the Biological Fate of Polymer-Coated Solid Nanoparticles

Polymer-coated inorganic nanoparticles (NPs) have attracted great attention in drug delivery fields due to their unique magnetic, optical, and thermal properties. Recent studies have shown that the surface physicochemical properties of these NPs, including the size, shape, shell hydration, protein corona, and so forth, affect their biological fate. However, there has been less attention on the effect of the drug loading amount on the biological activity of inorganic NPs. Here, we used upconverting NPs (UCNPs) as an inorganic nanocarrier model, coated them with a triblock terpolymer poly(poly(ethylene glycol) methyl ether methacrylate)-block-polymethacrylic acid-block-ethylene glycol methacrylate phosphate (PPEGMEMA-b-PMAA-b-PEGMP), and loaded them with different amounts of anticancer drug doxorubicin (DOX) by electrostatic interactions. Our results show that the UCNPs with the lowest DOX loading amount (1.32%) have the best biological behavior. We find that the effect of DOX loading on the biological behavior of UCNPs is dominated by polymer shell hydration and the protein corona. The lowest drug-loading UCNPs are more hydrated and have more albumin coronas around, which leads to an increasing effect on the association with cancer cells and drug accumulation in the mouse tumor area. Our findings highlight the importance of optimizing the drug loading amounts in polymer-coated inorganic drug delivery systems as the amount and type of drug will alter the physical properties of the polymer shell.

Persistence Length and Encounter Frequency Determination from Fluorescence Studies of Pyrene-Labeled Poly(oligo(ethylene glycol) methyl ether methacrylate)s

A series of nine pyrene-labeled poly(oligo(ethylene glycol) methyl ether methacrylate)s (Py-PEGnMAs) with n equal to 0–5, 9, 16, and 19 were prepared by random radical copolymerization of 1-pyrenebutyl methacrylate and nine different EGnMA monomers. The process of pyrene excimer formation (PEF) in the Py-PEGnMA samples was characterized in acetone, THF, toluene, N,N-dimethylformamide (DMF), dioxane, and dimethyl sulfoxide (DMSO). The fluorescence decays of all Py-PEGnMA samples were acquired in the six solvents and analyzed with the fluorescence blob model (FBM) to yield the number Nblob of structural units (SU) in the subvolume of the polymer coil probed by an excited pyrene and referred to as a blob, and the rate constant kblob describing the encounters between two SU bearing an excited and a ground-state pyrenyl label located inside a same blob. Nblob and kblob remained constant with pyrene content for a same series of Py-PEGnMA samples. After averaging Nblob and kblob over all pyrene contents for a same Py-PEGnMA series, ⟨Nblob⟩ and the product ⟨kblob × Nblob⟩ were found to decrease with increasing side chain length reflecting a progressive stiffening and decrease in the internal dynamics of the polymethacrylate backbone, respectively. ⟨Nblob⟩ and ⟨kblob × Nblob⟩ could be parametrized as a function of the molecular weight of an SU and the solvent viscosity. The parametrized form of ⟨Nblob⟩ was applied to determine the persistence length (lp) of the PEGnMA samples using the Kratky–Porod equation. lp was found to increase linearly with the square of the side chain length of the PEGnMA samples, as expected theoretically. The parametrized form of ⟨kblob × Nblob⟩ was used as a calibration curve against which the internal dynamics of several polypeptides and poly(methyl acrylate) could be compared in DMSO. This study illustrates the ability of PEF measurements to determine the persistence length and quantify the internal dynamics of polymers in solution, two important parameters in the characterization of macromolecules.

Antioxidant Polymers with Enhanced Neuroprotection Against Insulin Fibrillation.

Lipoic acid (LA) and dihydrolipoic acid (DHLA) are well established antioxidants to scavenge reactive oxygen species (ROS). However, they are carboxylates with ≈4.7pKa making them negatively charged at physiological pH (7.4) reducing their passive diffusion through cell membranes. LA is known to be capable of reducing protein fibrillation. Incorporation of LA and especially DHLA in polymer side chains are scarce. Herein, the first examples of the anti-amyloidogenic effect of LA and DHLA incorporated into the side-chain of a block copolymer with a water-soluble poly(polyethylene glycol methyl ether methacrylate) (PPEGMA) segment are presented. The resultant polymers show improved ROS scavenging activity and improved ability to reduce insulin fibrillation compared to free LA and DHLA. Furthermore, the resultant polymers are also capable of disintegrating preformed insulin firbrils. Interestingly, polymers with dihydro-lipoate moieties showed 93% free radical scavenging activity with 91% anti-fibrillating efficacies for insulin protein confirmed by 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay and Thioflavin T (ThT) dye binding study, respectively. Further, the antioxidant polymers increase the cell viability against fibrillar insulin aggregates that may be involved in the etiology of several diseases. Overall, this work reveals that antioxidant polymer-based therapeutic agents can serve as a powerful modulation strategy for developing novel drugs in future against amyloid-related disorders.

Visible-Light-Reactive Single-Chain Nanoparticles.

We introduce a single-chain nanoparticle (SCNP) system capable of catalyzing the photooxidation of nonpolar alkenes up to three times more efficiently than an equivalent small-molecule photosensitizer at an identical concentration. Specifically, we construct a polymer chain constituted of poly(ethylene glycol) methyl ether methacrylate and glycidyl methacrylate which we compact via multifunctional thiol-epoxide ligation and functionalize with Rose Bengal (RB) in a one pot reaction, affording SCNPs with a hydrophilic shell and hydrophobic photocatalytic regions. Photooxidation of the internal alkene in oleic acid proceeds under green light. RB confined within the SCNP is three times more effective for nonpolar alkenes than free RB in solution, which we hypothesize is due to the spatial proximity of the photosensitizing units to the substrate in the hydrophobic region. Our approach demonstrates that SCNP based catalysts can afford enhanced photocatalysis via confinement effects in a homogeneous reaction environment.

Einzelkettennanopartikel mit Reaktivität im sichtbaren Lichtspektrum

AbstractWir stellen ein Einzelkettennanopartikel (SCNP)‐System vor, welches bei identischer Konzentration die Photooxidation unpolarer Alkene bis zu dreimal effizienter katalysieren kann als ein äquivalenter niedermolekularer Photosensibilisator. Konkret haben wir SCNPs basierend auf Poly(ethylenglykol)methylethermethacrylat und Glycidylmethacrylat entwickelt, welches wir über multifunktionelle Thiol‐Epoxid‐Verknüpfungen in Kombination mit der Funktionalisierung mit Bengalrosa (RB) in einer Eintopfreaktion falten. Die SCNPs weisen sowohl eine hydrophile Hülle als auch hydrophobe photokatalytische Regionen auf. Die Photooxidation des innenliegenden Alkens der Ölsäure verläuft unter Einstrahlung von grünem Licht. Kovalent an die SCNPs gebundenes RB ist dreimal sensitiver gegenüber unpolaren Alkene als freies RB in Lösung. Dies ist unserer Hypothese nach auf die räumliche Nähe der photosensibilisierenden Gruppen zum Substrat in der hydrophoben Region zurückzuführen. Unser Ansatz zeigt, dass SCNP‐basierte Katalysatoren eine verbesserte Photokatalyse durch Einschränkungseffekte (confinement effects) in einer homogenen Reaktionsumgebung ermöglichen können.

Polymer-Grafted Cellulose Nanofibrils with Enhanced Interfacial Compatibility for Stronger Poly(lactic acid) Composites

Cellulose nanofibrils (CNFs) are a promising reinforcement for biodegradable composite matrices such as poly(lactic acid) (PLA), but they require commercially scalable drying methods that preserve their fibrillar morphology along with improved interfacial interactions with polymer matrices. In this work, a water-based grafting-through polymerization scheme to modify CNFs improved spray drying behavior and reinforcement capacity in PLA composites. All polymer modifications yielded CNFs with a more fibrillar morphology after spray drying, increasing specific surface area by up to 490% compared to unmodified CNFs, values similar to conventional freeze drying. Polymer-grafted CNFs in PLA composites improved the tensile strength by 16% at 20 wt % loading and stiffness by 22% at a 10 wt % loading with two different graft-polymer chemistries compared to unmodified CNF composites. Surface energy heterogeneity measurements of the reinforcements and PLA matrix were employed to understand the improvements in composite properties. Polymer modifications lowered the total surface energy of the CNFs, and calculated ratios of work of adhesion to work of cohesion suggested improved interfacial compatibility for four of the modified CNFs with PLA. Rheological oscillatory shear studies of the composites correlated solid-like melt behavior, as demonstrated by storage moduli dominance, with higher tensile strength. Thermal analysis of the composites revealed that excessive plasticization by the poly(oligoethylene glycol methyl ether methacrylate)-grafted sample potentially offset mechanical property improvements imparted by the more fibrillar morphology. This work provides an opportunity for large-scale manufacturing of CNF/PLA composites via an entirely aqueous modification scheme and industrially relevant spray drying process.

Stabilizing Zn anodes by constructing PEGMA protecting layers for high-performance Zn-ion batteries

As a promising candidate for grid-scale energy storage, rechargeable aqueous Zn-ion batteries (ZIBs) have many advantages including low cost, high safety, and environmental benignity. However, the Zn metal anode still suffers from severe dendrite and corrosion issues, hindering the practical application of ZIBs. Herein, we report a dense and uniform poly (ethylene glycol methyl ether methacrylate) (PEGMA) artificial protecting layer to alleviate these issues, by preventing the direct electrolyte/Zn anode contact while guiding the uniform migration of Zn2+ ions. Thanks to these merits, the cycling stability of Zn//Zn symmetrical cells is remarkably improved from 248 h up to 1096 h (at 1 mA cm−2 and 1 mAh cm−2), and the Coulombic efficiencies (CEs) of the Zn striping/plating reaction is increased from 85.9% to 99.1%. Furthermore, the potential application of this strategy is further demonstrated in Zn//iodine (I2) full batteries. Compared with the Bare-Zn//I2 batteries, the PEGMA-Zn//I2 full batteries deliver better CEs (99.5% vs. 99.3% in average at 0.2 A g−1), cycling stability (capacity retention: 89.0% vs. 74.7% after 4000 cycles at 1 A g−1) and shelf life (capacity retention: 78% vs. 71% after 50 h open-circuit storage), underscoring the application potential of this strategy in high-performance ZIBs.

Smart Poly(lactide)-b-poly(triethylene glycol methyl ether methacrylate) (PLA-b-PTEGMA) Block Copolymers: One-Pot Synthesis, Temperature Behavior, and Controlled Release of Paclitaxel.

This paper introduces a new class of amphiphilic block copolymers created by combining two polymers: polylactic acid (PLA), a biocompatible and biodegradable hydrophobic polyester used for cargo encapsulation, and a hydrophilic polymer composed of oligo ethylene glycol chains (triethylene glycol methyl ether methacrylate, TEGMA), which provides stability and repellent properties with added thermo-responsiveness. The PLA-b-PTEGMA block copolymers were synthesized using ring-opening polymerization (ROP) and reversible addition-fragmentation chain transfer (RAFT) polymerization (ROP-RAFT), resulting in varying ratios between the hydrophobic and hydrophilic blocks. Standard techniques, such as size exclusion chromatography (SEC) and 1H NMR spectroscopy, were used to characterize the block copolymers, while 1H NMR spectroscopy, 2D nuclear Overhauser effect spectroscopy (NOESY), and dynamic light scattering (DLS) were used to analyze the effect of the hydrophobic PLA block on the LCST of the PTEGMA block in aqueous solutions. The results show that the LCST values for the block copolymers decreased with increasing PLA content in the copolymer. The selected block copolymer presented LCST transitions at physiologically relevant temperatures, making it suitable for manufacturing nanoparticles (NPs) and drug encapsulation-release of the chemotherapeutic paclitaxel (PTX) via temperature-triggered drug release mechanism. The drug release profile was found to be temperature-dependent, with PTX release being sustained at all tested conditions, but substantially accelerated at 37 and 40 °C compared to 25 °C. The NPs were stable under simulated physiological conditions. These findings demonstrate that the addition of hydrophobic monomers, such as PLA, can tune the LCST temperatures of thermo-responsive polymers, and that PLA-b-PTEGMA copolymers have great potential for use in drug and gene delivery systems via temperature-triggered drug release mechanisms in biomedicine applications.

Grafting of Porous Conductive Fiber Mats with an Antifouling Polymer Brush by Means of Filtration-Based Surface Initiated ATRP.

This work addresses the challenge of surface modification of porous, electrospun fiber mats containing an insoluble conducting polymer coating. Herein, a novel methodology of grafting a polymer brush onto conducting polymer fiber mats is developed that employs filtering of the polymerization solution through the fiber mat. An electrospun sulfonated polystyrene-poly(ethylene-ran-butylene)-polystyrene (sSEBS) fiber mat is first coated with a layer of conducting copolymer bearing an Atom Transfer Radical Polymerization (ATRP) initiating functionality (PEDOT-Br). The surface-initiated ATRP from the fibers' surface is then carried out to graft a hydrophilic polymer brush (poly(ethylene glycol) methyl ether methacrylate) by means of filtering the polymerization solution through the fiber mat. Scanning electron microscopy (SEM) images reveal a progressive change in the morphology of the fiber mat surface with the increasing volume of the filtrated polymerization solution, while energy dispersive X-ray spectrosdcopy (EDX) spectra show a change in the atomic oxygen to sulfur (O/S) ratio, therefore confirming the successful grafting from the fibers' surface. The conductive fiber mat grafted with hydrophilic brushes shows a 20% reduction in the non-specific adsorption of bovine serum albumin (BSA) compared to a pristine fiber mat. This study is a proof-of-concept for this novel, filtration-based, surface-initiated polymerization methodology.

Proteinosomes via Self-Assembly of Thermoresponsive Miktoarm Polymer Protein Bioconjugates.

To fabricate nanoscale proteinosomes, thermoresponsive miktoarm polymer protein bioconjugates were prepared through highly efficient molecular recognition between the β-cyclodextrin modified BSA (CD-BSA) and the adamantyl group anchored at the junction point of the thermoresponsive block copolymer poly(ethylene glycol)-b-poly(di(ethylene glycol) methyl ether methacrylate) (PEG-b-PDEGMA). PEG-b-PDEGMA was synthesized by the Passerini reaction of benzaldehyde-modified PEG, 2-bromo-2-methylpropionic acid, and 1-isocyanoadamantane, followed by the atom transfer radical polymerization of DEGMA. Two block copolymers with different chain lengths of PDEGMA were prepared, and both self-assembled into polymersomes at a temperature above their lower critical solution temperatures (LCST). The two copolymers can undergo molecular recognition with the CD-BSA and form miktoarm star-like bioconjugates. The bioconjugates self-assembled into ∼160 nm proteinosomes at a temperature above their LCSTs, and the miktoarm star-like structure has a great effect on the formation of the proteinosomes. Most of the secondary structure and esterase activity of BSA in the proteinosomes were maintained. The proteinosomes exhibited low toxicity to the 4T1 cells and could deliver model drug doxorubicin into the 4T1 cells.

Chitosan Grafted with Thermoresponsive Poly(di(ethylene glycol) Methyl Ether Methacrylate) for Cell Culture Applications

Chitosan is a polysaccharide extracted from animal sources such as crab and shrimp shells. In this work, chitosan films were modified by grafting them with a thermoresponsive polymer, poly(di(ethylene glycol) methyl ether methacrylate) (PMEO2MA). The films were modified to introduce functional groups useful as reversible addition-fragmentation chain transfer (RAFT) agents. PMEO2MA chains were then grown from the films via RAFT polymerization, making the chitosan films thermoresponsive. The degree of substitution of the chitosan-based RAFT agent and the amount of monomer added in the grafting reaction were varied to control the length of the grafted PMEO2MA chain segments. The chains were cleaved from the film substrates for characterization using 1H NMR and a gel permeation chromatography analysis. Temperature-dependent contact angle measurements were used to demonstrate that the hydrophilic-hydrophobic nature of the film surface varied with temperature. Due to the enhanced hydrophobic character of PMEO2MA above its lower critical solution temperature (LCST), the ability of PMEO2MA-grafted chitosan films to serve as a substrate for cell growth at 37 °C (incubation temperature) was tested. Interactions with cells (fibroblasts, macrophages, and corneal epithelial cells) were assessed. The modified chitosan films supported cell viability and proliferation. As the temperature is lowered to 4 °C (refrigeration temperature, below the LCST), the grafted chitosan films become less hydrophobic, and cell adhesion should decrease, facilitating their removal from the surface. Our results indicated that the cells were detached from the films following a short incubation period at 4 °C, were viable, and retained their ability to proliferate.

Dynamic elastomers based on bio‐derived crosslinker

AbstractPetroleum‐derived monomers are the most common building blocks for ester‐based thermosets. Bio‐derived thermoset elastomers are becoming viable alternatives to conventional thermosets. Herein, we developed a biobased vitrimer‐type thermoset elastomers using abundant and sustainable raspberry ketone as feedstock. We utilize raspberry ketone to create building blocks for dynamic oxime chemistry and crosslinked these through free radical polymerization with poly(ethylene glycol) methyl ether methacrylate as a comonomer. In contrast to other dynamic networks based on ester bonds, which need catalysts, this is undesirable since catalyst deactivation or leaching lowers its effect over time and may impair reuse. This network incorporates catalyst‐free bond exchange reactions in catalyst‐dependent polyester networks by substituting oxime‐esters for typical ester linkages. The elastomer exhibits stress relaxation, a low glass transition temperature (Tg) (−55 to −40.2°C) and tensile strength up to 5.2 ± 3.0 kPa. Furthermore, the dynamic oxime transesterification exchange mechanism allows elastomers to be reprocessed using a hot press at 160°C and 8 × 103 kPa pressure. After reprocessing, the tensile strength of elastomers can be recovered up to 78.1 ± 10.9%. This work integrates the principles of catalyst‐free dynamic exchange process and mechanical recycling coupled with biobased components to provide a rational solution towards conventional elastomers. In the future, these elastomers can be exploited for the development of hydrogels, recyclable elastomers, and commodity plastics.

HER2-Specific Peptide (LTVSPWY) and Antibody (Herceptin) Targeted Core Cross-Linked Micelles for Breast Cancer: A Comparative Study.

This study aims to prepare a novel breast cancer-targeted micelle-based nanocarrier, which is stable in circulation, allowing intracellular drug release, and to investigate its cytotoxicity, apoptosis, and cytostatic effects, in vitro. The shell part of the micelle is composed of zwitterionic sulfobetaine ((N-3-sulfopropyl-N,N-dimethylamonium)ethyl methacrylate), while the core part is formed by another block, consisting of AEMA (2-aminoethyl methacrylamide), DEGMA (di(ethylene glycol) methyl ether methacrylate), and a vinyl-functionalized, acid-sensitive cross-linker. Following this, a targeting agent (peptide (LTVSPWY) and antibody (Herceptin®)), in varying amounts, were coupled to the micelles, and they were characterized by 1H NMR, FTIR (Fourier-transform infrared spectroscopy), Zetasizer, BCA protein assay, and fluorescence spectrophotometer. The cytotoxic, cytostatic, apoptotic, and genotoxic effects of doxorubicin-loaded micelles were investigated on SKBR-3 (human epidermal growth factor receptor 2 (HER2)-positive) and MCF10-A (HER2-negative). According to the results, peptide-carrying micelles showed a higher targeting efficiency and better cytostatic, apoptotic, and genotoxic activities than antibody-carrying and non-targeted micelles. Also, micelles masked the toxicity of naked DOX on healthy cells. In conclusion, this nanocarrier system has great potential to be used in different drug-targeting strategies, by changing targeting agents and drugs.

Nitroxide-Containing Amphiphilic Random Terpolymers for Marine Antifouling and Fouling-Release Coatings

Two types of amphiphilic random terpolymers, poly(ethylene glycol methyl ether methacrylate)-ran-poly(2,2,6,6-tetramethylpiperidinyloxy methacrylate)-ran-poly(polydimethyl siloxane methacrylate) (PEGMEMA-r-PTMA-r-PDMSMA), were synthesized and evaluated for antifouling (AF) and fouling-release (FR) properties using diverse marine fouling organisms. In the first stage of production, the two respective precursor amine terpolymers containing (2,2,6,6-tetramethyl-4-piperidyl methacrylate) units (PEGMEMA-r-PTMPM-r-PDMSMA) were synthesized by atom transfer radical polymerization using various comonomer ratios and two initiators: alkyl halide and fluoroalkyl halide. In the second stage, these were selectively oxidized to introduce nitroxide radical functionalities. Finally, the terpolymers were incorporated into a PDMS host matrix to create coatings. AF and FR properties were examined using the alga Ulva linza, the barnacle Balanus improvisus, and the tubeworm Ficopomatus enigmaticus. The effects of comonomer ratios on surface properties and fouling assay results for each set of coatings are discussed in detail. There were marked differences in the effectiveness of these systems against the different fouling organisms. The terpolymers had distinct advantages over monopolymeric systems across the different organisms, and the nonfluorinated PEG and nitroxide combination was identified as the most effective formulation against B. improvisus and F. enigmaticus.

Self-Aggregation in Aqueous Media of Amphiphilic Diblock and Random Block Copolymers Composed of Monomers with Long Side Chains.

Amphiphilic diblock copolymers and hydrophobically modified random block copolymers can self-assemble into different structures in a selective solvent. The formed structures depend on the copolymer properties, such as the ratio between the hydrophilic and the hydrophobic segments and their nature. In this work, we characterize by cryogenic transmission electron microscopy (cryo-TEM) and dynamic light scattering (DLS) the amphiphilic copolymers poly(2-dimethylamino ethyl methacrylate)-b-poly(lauryl methacrylate) (PDMAEMA-b-PLMA) and their quaternized derivatives QPDMAEMA-b-PLMA at different ratios between the hydrophilic and the hydrophobic segments. We present the various structures formed by these copolymers, including spherical and cylindrical micelles, as well as unilamellar and multilamellar vesicles. We also examined by these methods the random diblock copolymers poly(2-(dimethylamino) ethyl methacrylate)-b-poly(oligo(ethylene glycol) methyl ether methacrylate) (P(DMAEMA-co-Q6/12DMAEMA)-b-POEGMA), which are partially hydrophobically modified by iodohexane (Q6) or iodododecane (Q12). The polymers with a small POEGMA block did not form any specific nanostructure, while a polymer with a larger POEGMA block formed spherical and cylindrical micelles. This nanostructural characterization could lead to the efficient design and use of these polymers as carriers of hydrophobic or hydrophilic compounds for biomedical applications.

Mitochondria-Targeting Polyprodrugs to Overcome the Drug Resistance of Cancer Cells by Self-Amplified Oxidation-Triggered Drug Release.

The multi-drug resistance (MDR) of cancers is one of the main barriers for the success of diverse chemotherapeutic methods and is responsible for most cancer deaths. Developing efficient approaches to overcome MDR is still highly desirable for efficient chemotherapy of cancers. The delivery of targeted anticancer drugs that can interact with mitochondrial DNA is recognized as an effective strategy to reverse the MDR of cancers due to the relatively weak DNA-repairing capability in the mitochondria. Herein, we report on a polyprodrug that can sequentially target cancer cells and mitochondria using folic acid (FA) and tetraphenylphosphonium (TPP) targeting moieties, respectively. They were conjugated to the terminal groups of the amphiphilic block copolymer prodrugs composed of poly[oligo(ethylene glycol) methyl ether methacrylate] (POEGMA) and copolymerized monomers containing cinnamaldehyde (CNM) and doxorubicin (DOX). After self-assembly into micelles with the suitable size (∼30 nm), which were termed as TF@CNM + DOX, and upon intravenous administration, the micelles can accumulate in tumor tissues. After FA-mediated endocytosis, the endosomal acidity (∼pH 5) can trigger the release of CNM from TF@CNM + DOX micelles, followed by enhanced accumulation into the mitochondria via the TPP target. This promotes the overproduction of reactive oxygen species (ROS), which can subsequently enhance the intracellular oxidative stress and trigger ROS-responsive release of DOX into the mitochondria. TF@CNM + DOX shows great potential to inhibit the growth of DOX-resistant MCF-7 ADR tumors without observable side effects. Therefore, the tumor and mitochondria dual-targeting polyprodrug design represents an ideal strategy to treat MDR tumors through improvement of the intracellular oxidative level and ROS-responsive drug release.

3 stage filtration system utilizing 3 distinct membranes derived from one single dope solution and finely-tuned phase inversion processes

Wastewater treatment by membrane processes requires at least 3 different membranes with performances falling in the microfiltration, ultrafiltration and nanofiltration ranges. Often, the composition of these membranes varies, and their preparation processes may involve several steps and lengthy or costly post-treatment procedures, for instance to endow the membrane with fouling-resistance property. Here, we intended to explore potential routes to simplify the treatment process. We solely used one single casting solution with the purpose of preparing 3 membranes without any post-treatment, that were then implemented in a 3-stage filtration process. This solution contains polyvinylidene fluoride (PVDF), a copolymer of styrene and polyethylene glycol methyl ether methacrylate (PS-r-PEGMA), and a solvent. 3 phase inversion processes: vapor-induced phase separation (VIPS), liquid-induced phase separation (LIPS) and evaporation-induced phase separation (EIPS) were executed to reach the desired membrane properties. Careful examination of the membrane structure, physical properties and permeability prove that the membranes prepared by VIPS (pore size: 0.4–0.8 µm), LIPS (pore size: 0.008–0.09 µm) and a combination of EIPS and LIPS (pore size: 3–6 nm) were suitable for the rejection of large biofoulants such as microalgae, large and small proteins, respectively, despite the presence of the antifouling copolymer that affected the membrane structure. Next, the 3 membranes were used to treat synthetic wastewater containing a mixture of microalgae, bovine serum albumin (BSA) and lysozyme. The first filtration stage permitted to reject almost entirely the Microalgae (99.3–99.5% rejection), the second filtration stage then removed larger proteins (cumulated “Microalgae/protein” rejection of about 93%) while the last stage rejected a large quantity of the smaller protein. The copolymer was also shown to reduce fouling by a 5-fold factor. Hence, this work demonstrates that a complete set of pressure-driven antifouling membranes for full wastewater treatment may be prepared from one single formulation and by phase inversion only.