Regulating the Chiroptical Expression of Aggregated Solvophobic Core by Solvophilic Segments.

The investigation of chiral supramolecular stacking is of essential significance for the understanding of the origin of homochirality in nature. Unlike structurally well-defined amphiphilic liposomes, it remains unclear whether the solvophilic segments of the amphiphilic block copolymer play a decisive role in the construction of asymmetric superstructures. Herein, insights are presented into the stacking patterns and morphological regulation in azobenzene-containing block copolymer assemblies solely by modulating the solvophilic chain length. The solvophilic poly(methacrylic acid) (PMAA) segments of different molecular weights could cause multi-mode chirality inversions involving stacking transitions between intra-chain π-π stacking, inter-chain H- and J-aggregation. Furthermore, the length of the solvophilic PMAA also affects the morphology of the chiral supramolecular assemblies; rice grain-like micelles, worms, nanofibers, floccules, and lamellae can be prepared at different solvophilic-solvophobic balance. The comprehensive mechanism is collectively revealed by utilizing various measurement methods, such as including circular dichroism (CD), small-angle X-ray scattering (SAXS), and wide-angle X-ray diffraction (WAXD). This study highlights the critical importance of fully dissolved solvophilic segments for the chiroptical regulation of the aggregated core, providing new insights into the arrangement of chiral supramolecular structures in polymer systems.

Organic Donor-Acceptor-Donor Trimers Nanoparticles Stabilized by Amphiphilic Block Copolymers for Photocatalytic Generation of H2.

Photocatalytic generation of H2 via water splitting emerges as a promising avenue for the next generation of green hydrogen due to its low carbon footprint. Herein, a versatile platform is designed to the preparation of functional π-conjugated organic nanoparticles dispersed in aqueous phase via mini-emulsification. Such particles are composed of donor-acceptor-donor (DAD) trimers prepared via Stille coupling, stabilized by amphiphilic block copolymers synthesized by reversible addition-fragmentation chain transfer polymerization. The hydrophilic segment of the block copolymers will not only provide colloidal stability, but also allow for precise control over the surface functionalization. Photocatalytic tests of the resulting particles for H2 production resulted in promising photocatalytic activity (≈0.6 mmol g-1 h-1). This activity is much enhanced compared to that of DAD trimers dispersed in the water phase without stabilization by the block copolymers.

Crystallization-Driven Controlled 2D Self-Assemblies via Aqueous RAFT Emulsion Polymerization.

Aqueous emulsion polymerization is a robust technique for preparing nanoparticles of block copolymers; however, it typically yields spherical nanoassemblies. The scale preparation of nanoassemblies with nonspherical high-order morphologies is a challenge, particularly 2D core-shell nanosheets. In this study, the polymerization-induced self-assembly (PISA) and crystallization-driven self-assembly (CDSA) are combined to demonstrate the preparation of 2D nanosheets and their aggregates via aqueous reversible addition-fragmentation chain transfer (RAFT) emulsion polymerization. First, the crucial crystallizable component for CDSA, hydroxyethyl methacrylate polycaprolactone (HPCL) macromonomer is synthesized by ring opening polymerization (ROP). Subsequently, the RAFT emulsion polymerization of HPCL is conducted to generate crystallizable nanomicelles by a grafting-through approach. This PISA process simultaneously prepared spherical latices and bottlebrush block copolymers comprising poly(N',N'-dimethylacrylamide)-block-poly(hydroxyethyl methacrylate polycaprolactone) (PDMA-b-PHPCL). The latexes are now served as seeds for inducing the formation of 2D hexagonal nanosheets, bundle-shaped and flower-like aggregation via the CDSA of PHPCL segments and unreacted HPCL during cooling. Electron microscope analysis trace the morphology evolution of these 2D nanoparticles and reveal that an appropriate crystallized component of PHPCL blocks play a pivotal role in forming a hierarchical structure. This work demonstrates significant potential for large-scale production of 2D nanoassemblies through RAFT emulsion polymerization.

Temperature-Sensitive Materials for Oil and Gas Drilling Applications.

With the vigorous development of the petroleum industry, improving the efficiency of oil and gas exploitation has become an important issue. Temperature-sensitive materials show great potential for application in the development and production of oil and gas fields due to their unique temperature-responsive properties. This paper reviews the application of temperature-sensitive materials in oil and gas drilling and introduces the characteristics of three types of temperature-sensitive materials: N-substituted acrylamide polymers, amphiphilic block copolymers, and peptides. Because these materials can change their physical state at specific temperatures, this paper discusses in detail the role of various temperature-sensitive materials as plugging agent, thickener, oil displacing agent, flocculant, and tackifier in oil and gas field operations, as well as the mechanism of action and performance of temperature-sensitive materials in practical oil and gas drilling operations. As we have not yet seen relevant similar literature, this paper aims to discuss the innovative application of temperature-sensitive materials in the oil and gas drilling process, and at the same time points out the problems in the current research and applications as well as future development directions. Through analysis and comparison, we provide an efficient and environmentally friendly materials selection option for the petroleum industry in order to promote the progress and sustainable development of oil and gas extraction processes.

Multicomponent Copolymer Planar Membranes with Nanoscale Domain Separation.

Domain separation is crucial for proper cellular function and numerous biomedical technologies, especially artificial cells. While phase separation in hybrid membranes containing lipids and copolymers is well-known, the membranes' overall stability, limited by the lipid part, is hindering the technological applications. Here, we introduce a fully synthetic planar membrane undergoing phase separation into domains embedded within a continuous phase. The mono- and bilayer membranes are composed of two amphiphilic diblock copolymers (PEO45-b-PEHOx20 and PMOXA10-b-PDMS25) with distinct properties and mixed at various concentrations. The molar ratio of the copolymers in the mixture and the nature of the solid support were the key parameters inducing nanoscale phase separation of the planar membranes. The size of the domains and resulting morphology of the nanopatterned surfaces were tailored by adjusting the molar ratios of the copolymers and transfer conditions. Our approach opens new avenues for the development of biomimetic planar membranes with a nanoscale texture.

Curcumin-Loaded PnBA-b-POEGA Nanoformulations: A Study of Drug-Polymer Interactions and Release Behavior.

The current study focuses on the development of innovative and highly-stable curcumin (CUR)-based therapeutics by encapsulating CUR in biocompatible poly(n-butyl acrylate)-block-poly(oligo(ethylene glycol) methyl ether acrylate) (PnBA-b-POEGA) micelles. State-of-the-art methods were used to investigate the encapsulation of CUR in PnBA-b-POEGA micelles and the potential of ultrasound to enhance the release of encapsulated CUR. Dynamic light scattering (DLS), attenuated total reflection Fourier transform infrared (ATR-FTIR), and ultraviolet-visible (UV-Vis) spectroscopies confirmed the successful encapsulation of CUR within the hydrophobic domains of the copolymers, resulting in the formation of distinct and robust drug/polymer nanostructures. The exceptional stability of the CUR-loaded PnBA-b-POEGA nanocarriers over a period of 210 days was also demonstrated by proton nuclear magnetic resonance (1H-NMR) spectroscopy studies. A comprehensive 2D NMR characterization of the CUR-loaded nanocarriers authenticated the presence of CUR within the micelles, and unveiled the intricate nature of the drug-polymer intermolecular interactions. The UV-Vis results also indicated high encapsulation efficiency values for the CUR-loaded nanocarriers and revealed a significant influence of ultrasound on the release profile of CUR. The present research provides new understanding of the encapsulation and release mechanisms of CUR within biocompatible diblock copolymers and has significant implications for the advancement of safe and effective CUR-based therapeutics.

Nanomicelles Array for Ultrahigh-Density Data Storage.

High-density data storage devices based on organic and polymer materials are currently restricted by two key issues, size limitations and uniformity of memory cells. Herein, one triblock polymer is synthesized by ring-opening metathesis polymerization, where the polymer contains an electron-donor-acceptor (A1 D) segment, an electron-acceptor (A2 ) segment, and a hydrophilic segment, that shows ternary memory behavior in a conventional sandwich-type device. The polymers that have monodisperse molecular weight dispersity self-assemble into nanomicelles with a uniform size of 80 nm. Each nanomicelle is composed of an A1 DA2 -type hydrophobic core stabilized with a hydrophilic shell. Nanobowls based on conductive oxide are prepared via the template method, wherein the nanomicelles are present as independent nanoscale memory units to produce an array of micelle matrices. Investigations of the resulting nanomemory device using conductive atomic force microscopy show that the micelles exhibit a predominant semiconductor memory behavior. Compared to traditional ternary devices with a memory unit size of ≈1 mm, this innovative fabrication method based on arrayed uniform nanomicelles downscales the size of storage cells to 80 nm. Furthermore, the described system leads to a greatly enhanced storage density (>108 times over the same area), which opens up new paths for further development of ultrahigh-density data storage devices.

Recent Progress in Polymer Cubosomes and Hexosomes.

Polymer cubosomes and hexosomes are polymer colloids with inverted lyotropic liquid crystal phases as internal structures. They are composed of regular networks of water-filled channels surrounded by a bilayer membrane made from amphiphilic block copolymers. Due to the uniform, tunable, and highly ordered porous structure, polymer cubosomes and hexosomes present numerous advantages over polymer micelles and vesicles, such as the high loading volumes for both hydrophilic and hydrophobic substances, large specific surface areas, and good mechanical and chemical stabilities. The polymer chemistry also enables unlimited molecular design to endow these polymer colloids with a lot of adjustable physical and chemical properties. Therefore, polymer cubosomes and hexosomes have attracted increasing attention for their potential applications in materials science and nanotechnology. This review outlines the recent progress in this field with an emphasis on the polymer architectures, the self-assembly conditions and mechanisms, and some application examples which are special for these inverted polymer colloids. It is hoped to provide some practical guidance for researchers interested in polymer cubosomes and hexosomes.

Imidazole-Mediated Dual Location Disassembly of Acid-Degradable Intracellular Drug Delivery Block Copolymer Nanoassemblies.

Acid-degradable (or acid-cleavable) polymeric nanoassemblies have witnessed significant progress in anti-cancer drug delivery. However, conventional nanoassemblies designed with acid-cleavable linkages at a single location have several challenges, such as, sluggish degradation, undesired aggregation of degraded products, and difficulty in controlled and on-demand drug release. Herein, a strategy that enables the synthesis of acid-cleavable nanoassemblies labeled with acetaldehyde acetal groups in both hydrophobic cores and at core/corona interfaces, exhibiting synergistic response to acidic pH at dual locations and thus inducing rapid drug release is reported. The systematic analyses suggest that the acid-catalyzed degradation and disassembly are further enhanced by decreasing copolymer concentration (i.e., increasing proton/acetal mole ratio). Moreover, incorporation of acid-ionizable imidazole pendants in the hydrophobic cores improve the encapsulation of doxorubicin, the anticancer drug, through π-π interactions and enhance the acid-catalyzed hydrolysis of acetal linkages situated in the dual locations. Furthermore, the presence of the imidazole pendants induce the occurrence of core-crosslinking that compensates the kinetics of acetal hydrolysis and drug release. These results, combined with in vitro cell toxicity and cellular uptake, suggest the versatility of the dual location acid-degradation strategy in the design and development of effective intracellular drug delivery nanocarriers.

Amphiphilic Block Copolymers: A Novel Substance for Bitter-Masking in Aqueous Solutions.

It is a challenging task to suppress the bitterness of liquid preparations, especially for children. Bitter molecules are highly dispersible in liquids, leading to a strong and instant stimulation of the bitter receptors. At present, there is no effective way to correct this issue except for adding sweeteners, resulting in an unsatisfying taste. Based on the three-point contact theory, which is a universally accepted mechanism of bitterness formation, a new idea and application of amphiphilic block copolymers (ABCs) for bitterness suppression was proposed for the first time. We found that ABCs could widely inhibit the bitterness of four typical bitter substances. The mechanism is that ABCs self-assemble to form association colloids, which attract bitter components and reduce their distribution in the molecular form in solution. The bitter components were demonstrated to automatically embed in the spiral hydrophobic cavity of the hydrophobic chain of the ABCs, and their special interaction dispersed the positive electrostatic potential of bitter groups. The combination did not affect the pharmacokinetic parameters and pharmacodynamics of bitter drugs. These findings highlight the novel application of ABCs for the inhibition of bitterness and illuminate the underlying inhibition mechanisms.

Redox-Initiated Reversible Addition-Fragmentation Chain Transfer (RAFT) Miniemulsion Polymerization of Styrene using PPEGMA-Based Macro-RAFT Agent.

Redox-initiated reversible addition-fragmentation chain transfer (RAFT) miniemulsion polymerizations are successfully conducted with an employment of trithiocarbonate-based macro-RAFT agents and surfactant. Two macro-RAFT agents-hydrophilic poly(poly(ethylene glycol) methyl ether methacrylate) (PPEGMA27 ) and amphiphilic poly(poly(ethylene glycol) methyl ether methacrylate)-b-polystyrene (PPEGMA27 -b-PS33 )- are examined for the miniemulsion polymerization of styrene. The use of PPEGMA27 (in the presence of sodium dodecyl sulfate (SDS)) results in a slow polymerization rate with a broad particle size. In the absence of SDS, the use of PPEGMA27 -b-PS33 results in a broad particle size distribution due to its inability to form uniform initial droplets whereas the same amphiphilic block copolymer in the presence of SDS yields resulting products with a uniform particle size distribution. The latter exhibits a fashion of controlled polymerization with a high consumption of monomer (98% in 100 min) and a narrow molecular weight distribution throughout the polymerization. This is attributed to the formation of uniform droplets facilitated by SDS in a miniemulsion. The amphiphilic macro-RAFT agent is able to anchor efficiently on the monomer droplet or particle/water interface and form stabilized particles of well-defined PPEGMA27 -b-PS block copolymer, confirmed using dynamic light scattering and transmission electron micrographs.

Block Copolymers Featuring Highly Photostable Photoacids Based on Vinylnaphthol: Synthesis and Self-Assembly.

The synthesis of a photoresponsive amphiphilic diblock quarterpolymer containing 5-vinyl-1-naphthol (VN) as a photostable photoacidic comonomer is presented. The preparation is realized via a sequential reversible addition fragmentation chain transfer (RAFT) polymerization starting from a nona(ethylene glycol) methyl ether methacrylate (MEO9 MA/"O") hydrophilic block, which is then used as a macro-RAFT agent in the terpolymerization of styrene (S), 2-vinylpyridine (2VP), and TBS-protected VN (tVN). The terpolymerization proceeds in a controlled fashion and two diblock quarterpolymers, P(Om )-b-P(Sx -co-2VPy -co-VNz ), with varying functional comonomer compositions are prepared. These diblock quarterpolymers form spherical core-corona micelles in aqueous media according to dynamic light scattering (DLS) and cryogenic transmission electron microscopy (cryo-TEM). Upon irradiation, the photoacids within the micellar core experience a drastic increase in acidity causing a proton transfer from the photoacid to neighboring 2VP units. As a result, the hydrophilic/hydrophobic balance of the entire assembly is shifted, and the encapsulated cargo is released.

Direct Polymerization Approach to Synthesize Acid-Degradable Block Copolymers Bearing Imine Pendants for Tunable pH-Sensitivity and Enhanced Release.

The development of effective approaches to synthesize smart amphiphilic block copolymers (ABPs) exhibiting acid-responsive degradation through the cleavage of acid-labile imine bonds is extensively explored for controlled release of encapsulated biomolecules, particularly in drug delivery. Here, a new approach based on direct polymerization utilizing a controlled radical polymerization technique to synthesize acid-degradable ABPs bearing pendant imine linkages in hydrophobic block is reported. The approach centers on the synthesis of a novel methacrylate bearing benzoic imine group that can be polymerized to form the hydrophobic imine pendant block. The formed ABPs respond to mild acidic pHs equivalent to tumoral and endosomal/lysosomal acidic environments. This causes the dissociation of self-assembled nanoassemblies through change in their hydrophilic/hydrophobic balance upon the cleavage of pendant imine linkages to the corresponding aldehyde and primary amine, thus leading to the enhanced release of encapsulated drugs. The proof-of-concept results suggest that this robust approach is versatile to further design advanced nanoassemblies responding to dual/multiple stimuli, thus being more effective to intracellular drug delivery.

High-Fidelity End-Functionalization of Poly(ethylene glycol) Using Stable and Potent Carbamate Linkages.

Commercial PEG-amine is of unreliable quality, and conventional PEG functionalization relies on esterification and etherification steps, suffering from incomplete conversion, harsh reaction conditions, and functional-group incompatibility. To solve these challenges, we propose an efficient strategy for PEG functionalization with carbamate linkages. By fine-tuning terminal amine basicity, stable and high-fidelity PEG-amine with carbamate linkage was obtained, as seen from the clean MALDI-TOF MS pattern. The carbamate strategy was further applied to the synthesis of high-fidelity multi-functionalized PEG with varying reactive groups. Compared to with an ester linkage, amphiphilic PEG-PS block copolymers bearing carbamate junction linkage exhibits preferential self-assembly tendency into vesicles. Moreover, nanoparticles of the latter demonstrate higher drug loading efficiency, encapsulation stability against enzymatic hydrolysis, and improved in vivo retention at the tumor region.

pH-Driven Morphological Diversity in Poly[n-Butyl Acrylate-block-(2-(Dimethylamino)Ethyl Acrylate)] Amphiphilic Copolymer Solutions.

Amphiphilic poly[n-butyl acrylate-block-(2-(dimethylamino)ethyl acrylate)] (PnBA-b-PDMAEA) block copolymers are synthesized by the reversible addition fragmentation chain transfer polymerization process. The pH-responsive self-assembly behavior in aqueous media is studied by dynamic, static, and electrophoretic light scattering and cryogenic transmission electron microscopy (Cryo-TEM) at different pHs. In particular, the PnBA40 -b-PDMAEA60 copolymer (where subscripts denote %wt composition of the components) shows remarkable morphological transitions in aqueous solutions of varying pH values forming, among others, an unusual and novel hierarchical vesicular morphology, as indicated by Cryo-TEM results. The observed transitions are attributed to synergistic effects involving alterations of the protonation degree of the PDMAEA block, in conjunction with the specific composition of the copolymer and the softness of PnBA blocks, with cumulative drive changes in the packing parameter of the copolymer system and result in the formation of various unexpected morphologies by simple pH changes.

Quality-by-Design Approach for Biological API Encapsulation into Polymersomes Using "Off-the-Shelf" Materials: a Study on L-Asparaginase.

Polymersomes are versatile nanostructures for protein delivery with hydrophilic core suitable for large biomolecule encapsulation and protective stable corona. Nonetheless, pharmaceutical products based on polymersomes are not available in the market, yet. Here, using commercially available copolymers, we investigated the encapsulation of the active pharmaceutical ingredient (API) L-asparaginase, an enzyme used to treat acute lymphoblastic leukemia, in polymersomes through a quality-by-design (QbD) approach. This allows for streamlining of processes required for improved bioavailability and pharmaceutical activity. Polymersomes were prepared by bottom-up (temperature switch) and top-down (film hydration) methods employing the diblock copolymers poly(ethylene oxide)-poly(lactic acid) (PEG45-PLA69, PEG114-PLA153, and PEG114-PLA180) and the triblock Pluronic® L-121 (poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide), PEG5-PPO68-PEG5). Quality Target Product Profile (QTPP), Critical Quality Attributes (CQAs), Critical Process Parameters (CPPs), and the risk assessment were discussed for the early phase of polymersome development. An Ishikawa diagram was elaborated focusing on analytical methods, raw materials, and processes for polymersome preparation and L-asparaginase encapsulation. PEG-PLA resulted in diluted polymersomes systems. Nonetheless, a much higher yield of Pluronic® L-121 polymersomes of 200 nm were produced by temperature switch, reaching 5% encapsulation efficiency. Based on these results, a risk estimation matrix was created for an initial risk assessment, which can help in the future development of other polymersome systems with biological APIs nanoencapsulated.

Chromatographic characterization of amphiphilic di- and tri-block copolymers of poly(ethylene oxide) and poly(ε-caprolactone).

Amphiphilic di- and tri-block copolymers based on poly(ethylene oxide) as a hydrophilic segment and poly(ε-caprolactone) as a hydrophobic part are synthesized by the ring-opening polymerization of ε-caprolactone while using poly(ethylene glycol)s and methoxy poly(ethylene glycol)s of varying molar masses as macro-initiators. The synthesized block copolymers are characterized with respect to their total relative molar mass and its distribution by size exclusion chromatography. Liquid chromatography at critical conditions of both blocks is established for the analysis of individual block lengths and tracking presence of unwanted homopolymers of both types in the block copolymer samples. New critical conditions of polycaprolactone on reversed phase column are reported using organic mobile phase. The established critical conditions of polycaprolactone extended the applicable molar mass range significantly compared to already reported critical conditions of polycaprolactone in aqueous mobile phase. Block copolymers are also analyzed at critical conditions of poly(ethylene glycol). Complete analysis of the di- and tri-block copolymers at corresponding critical conditions provided a fair estimate of molar mass of non-critical block besides information regarding presence of homopolymers of both types in the samples.

Aqueous Self-Assembly of Y-Shaped Amphiphilic Block Copolymers into Giant Vesicles.

The preparation and aqueous self-assembly of newly Y-shaped amphiphilic block polyurethane (PUG) copolymers are reported here. These amphiphilic copolymers, designed to have two hydrophilic poly(ethylene oxide) (PEO) tails and one hydrophobic alkyl tail via a two-step coupling reaction, can self-assemble into giant unilamellar vesicles (GUVs) (diameter ≥ 1000 nm) with a direct dissolution method in aqueous solution, depending on their Y-shaped structures and initial concentrations. More interesting, the copolymers can self-assemble into various distinct nano-/microstructures, such as spherical micelles, small vesicles, and GUVs, with the increase of their concentrations. The traditional preparation methods of GUVs generally need conventional amphiphilic molecules and additional complicated conditions, such as alternating electrical field, buffer solution, or organic solvent. Therefore, the self-assembly of Y-shaped PUGs with a direct dissolution method in aqueous solution demonstrated in this study supplies a new clue to fabricate GUVs based on the geometric design of amphiphilic polymers.

Dynamics of Membrane Proteins within Synthetic Polymer Membranes with Large Hydrophobic Mismatch.

The functioning of biological membrane proteins (MPs) within synthetic block copolymer membranes is an intriguing phenomenon that is believed to offer great potential for applications in life and medical sciences and engineering. The question why biological MPs are able to function in this completely artificial environment is still unresolved by any experimental data. Here, we have analyzed the lateral diffusion properties of different sized MPs within poly(dimethylsiloxane) (PDMS)-containing amphiphilic block copolymer membranes of membrane thicknesses between 9 and 13 nm, which results in a hydrophobic mismatch between the membrane thickness and the size of the proteins of 3.3-7.1 nm (3.5-5 times). We show that the high flexibility of PDMS, which provides membrane fluidities similar to phospholipid bilayers, is the key-factor for MP incorporation.

The effect of self-assembly conditions on the size of di- and tri-block copolymer micelles: solicitation from response surface methodology.

The objective of this study was to assess the application of Response Surface Methodology in defining the effect of self-assembly condition on the average diameter of polymeric micelles. Di- and tri-block copolymers of poly(ethylene oxide)-b-poly(α-benzylcarboxylate-ε-caprolactone) (PEO-PBCL) and PBCL-b-poly(ethylene glycol)-b-PBCL (PBCL-PEG-PBCL) were synthesized through ring opening polymerization of α-benzyl-ɛ-carboxylate using MePEO or dihydroxy PEG as initiator, respectively. Polymeric micelles were formed through solubilization of block copolymers in acetone followed by drop-wise addition of this solution to water. Polymer concentration was changed and the intensity mean diameter of self-assembled structures was measured by dynamic light scattering. The experimental data were fitted to a mathematical model. The experimental conditions leading to the production of micelles of certain size (30, 60 or 90 nm for tri-block and 30 nm for di-block copolymers) was predicted. A good match between predicted and experimental data was observed. The results showed it would be possible to obtain micelles of certain size using block copolymers of different molecular weights or obtain micelles of different size at a given block copolymer molecular weight, by manipulating the polymer concentration. These observations show reproducible micelles of defined average diameter can be prepared by co-solvent evaporation by controlling the used polymer concentration.