Self-assembly Of Copolymers Research Articles

Chemiluminescent Conjugated Polymer Nanoparticles for Deep-Tissue Inflammation Imaging and Photodynamic Therapy of Cancer.

Deep-tissue optical imaging and photodynamic therapy (PDT) remain a big challenge for the diagnosis and treatment of cancer. Chemiluminescence (CL) has emerged as a promising tool for biological imaging and in vivo therapy. The development of covalent-binding chemiluminescence agents with high stability and high chemiluminescence resonance energy transfer (CRET) efficiency is urgent. Herein, we design and synthesize an unprecedented chemiluminescent conjugated polymer PFV-Luminol, which consists of conjugated polyfluorene vinylene (PFV) main chains and isoluminol-modified side chains. Notably, isoluminol groups with chemiluminescent ability are covalently linked to main chains by amide bonds, which dramatically narrow their distance, greatly improving the CRET efficiency. In the presence of pathologically high levels of various reactive oxygen species (ROS), especially singlet oxygen (1O2), PFV-Luminol emits strong fluorescence and produces more ROS. Furthermore, we construct the PFV-L@PEG-NPs and PFV-L@PEG-FA-NPs nanoparticles by self-assembly of PFV-Luminol and amphiphilic copolymer DSPE-PEG/DSPE-PEG-FA. The chemiluminescent PFV-L@PEG-NPs nanoparticles exhibit excellent capabilities for in vivo imaging in different inflammatory animal models with great tissue penetration and resolution. In addition, PFV-L@PEG-FA-NPs nanoparticles show both sensitive in vivo chemiluminescence imaging and efficient chemiluminescence-mediated PDT for antitumors. This study paves the way for the design of chemiluminescent probes and their applications in the diagnosis and therapy of diseases.

Relationship between molecular structure and corrugations in self-assembled polypeptoid nanosheets revealed by cryogenic electron microscopy

Designing conformationally dynamic molecules that self-assemble into predictable nanostructures remains an important unmet challenge. This paper describes how atomic-scale cryogenic transmission electron microscopy (cryo-TEM) can be used to explore the relationship between molecular structure and self-assembly of block copolymers. We examined sheetlike micelles formed in water using a series of diblock copolypeptoids with the same hydrophilic block and three distinct crystalline hydrophobic blocks. Our cryo-TEM images revealed all the structures share nansoscale features, but differ in their intermolecular packing geometries. Different molecular arrangements, parallel and antiparallel V-shaped crystal motifs, were revealed by two-dimensional atomic-scale through-plane images. However, images from tilted samples revealed an unexpected feature when the hydrophobic polypeptoid block comprised phenyl rings with substituted bromine atoms at the para position. The nanosheets contained atomic-scale corrugations that were absent in the other systems which comprised unsubstituted aliphatic and aromatic side chains. We hypothesize that these corrugations are due to the dipolar characteristics of the brominated phenyl group and interactions between this group and water molecules. Published by the American Physical Society 2024

Helical Superstructures from the Hierarchical Self-Assembly of Coil-Coil Block Copolymer Guided by Side Chain Amyloid-β(17-19) LVF Peptide.

The rational design of precisely controlled hierarchical chiral nanostructures from synthetic polymers garnered inspiration from sophisticated biological materials. Since chiral peptide motifs induce helix formation in macromolecules, herein we report the synthesis of a novel type of hybrid polymer consisting of a β-sheet forming a LVF [L = leucine, V = valine, and F = phenylalanine] tripeptide pendant polymethacrylate block and a poly[poly(ethylene glycol) methyl ether methacrylate] (PPEGMA) block. The designed block copolymer self-organized into helical superstructures with a left-handed twisting sense, as visualized by field emission scanning electron microscopy, transmission electron microscopy, and atomic force microscopy. This intriguing hierarchical self-assembly is driven by the minimalistic peptide motif that itself has a high propensity to adopt an antiparallel β-sheet conformation. We also report the generation of a diverse array of nanostructures, including spherical micelles, spindle micelles, rod-like micelles, vesicles, helical supramolecular fibers, and helical toroids via self-assembly of the designed block copolymer in tetrahydrofuran/water mixed solvents. To realize the observable helical superstructure, a twisted two-dimensional core-shell tape is proposed as a structure model in which the peptide segments form an antiparallel β-sheet with a polymer shell. The findings contribute to the advancement of a helical polymer or the superhelical self-assembly of polymers, paving the way for diverse applications in materials science and related fields.

Preparation of Block Copolymer Self-Assemblies via Pisa in a Non-Polar Medium Based on RCMP.

Polymerization-induced self-assembly (PISA) is conducted in a non-polar medium (n-dodecane) via reversible complexation-mediated polymerization (RCMP). Stearyl methacrylate (SMA) is used to synthesize a macroinitiator, and subsequent block polymerization of benzyl methacrylate (BzMA) from the macroinitiator in n-dodecane afforded a PSMA-PBzMA block copolymer, where PSMA is poly(stearyl methacrylate) and PBzMA is poly(benzyl methacrylate). Because PSMA is soluble but PBzMA is insoluble in n-dodecane, the block copolymer formed a self-assembly during the block polymerization (PISA). Spherical micelles, worms, and vesicles are obtained, depending on the degrees of polymerization of PSMA and PBzMA. "One-pot" PISA is also attained; namely, BzMA is directly added to the reaction mixture of the macroinitiator synthesis, and PISA is conducted in the same pot without purification of the macroinitiator. The spherical micelle and vesicle structures are also fixed using a crosslinkable monomer during PISA. RCMP-PISA is highly attractive as it is odorless and metal-free. The "one-pot" synthesis does not require the purification of the macroinitiator. RCMP-PISA can provide a practical approach to synthesize self-assemblies in non-polar media.

Morphology and thermal transitions of self-assembled NIPAM-DMA copolymers in aqueous media depend on copolymer composition profile

HypothesisThere is a lack of understanding of the interplay between the copolymer composition profile and thermal transition observed in aqueous solutions of N-isopropyl acrylamide (NIPAM) copolymers, as well as the correlation between this transition and the formation and structure of copolymer self-assemblies. ExperimentsFor this purpose, we investigated the response of five copolymers with the same molar mass and chemical composition, but with different composition profile in aqueous solution against temperature. Using complementary analytical techniques, we probed structural properties at different length scales, from the molecular scale with Nuclear Magnetic Resonance (NMR) to the colloidal scale with Dynamic Light Scattering (DLS) and Small Angle Neutron Scattering (SANS). FindingsNMR and SANS investigations strengthen each other and allow a clear picture of the change of copolymer solubility and related copolymer self-assembly as a function of temperature. At the molecular scale, dehydrating NIPAM units drag N,N-dimethyl acrylamide (DMA) moieties with them in a gradual collapse of the copolymer chain; this induces a morphological transition of the self-assemblies from star-like nanostructures to crew-cut micelles. Interestingly, the transition spans a temperature range which depends on the monomer distribution profile in the copolymer chain, with the asymmetric triblock copolymer specimen revealing the broadest one. We show that the broad morphological transitions associated with gradient copolymers can be mimicked and even surpassed by the use of stepwise gradient (asymmetric) copolymers, which can be more easily and reproducibly synthesized than linear gradient copolymers.

One-Pot Synthesis, Circularly Polarized Luminescence, and Controlled Self-Assembly of Janus-Type Miktoarm Star Copolymers.

With the aim of broadening the scope of Janus-type polymers with new functionalities, Janus-type miktoarm star copolymers comprising helical poly(phenyl isocyanide) (PPI) and a vinyl polymer were designed and synthesized via a combination of Pd(II)-initiated isocyanide polymerization and atom transfer radical polymerization (ATRP). A functional β-cyclodextrin bearing 7 Pd(II) complexes at one side and 14 bromine groups at the other side ((Pd(II))7-CD-(Br)14) was prepared and used as an initiator for the one-pot polymerization of phenyl isocyanide and the ATRP of vinyl monomers in a living and controlled manner. A variety of Janus-type copolymers with different structures and tunable compositions were facilely obtained by using this method. Thus, Janus-type copolymers composed of helical PPIs and tetraphenylethylene-modified vinyl polymers exhibited a significant circularly polarized luminescence performance in both soluble and aggregated states. Meanwhile, Janus-type copolymers containing PPIs and hydrophilic vinyl polymers presented amphiphilicity and self-assembled into diverse morphologies.

Enhanced Adsorption Stability and Biofunction Durability with Phosphonate-Grafted, PEGylated Copolymer on Hydroxyapatite Surface.

Nonfouling surfaces are crucial in applications such as biosensors, medical implants, marine coatings, and drug delivery vehicles. However, their long-term coating stability and robust surface binding strength in physiological media remain challenging. Herein, a phosphonate-grafted, PEGylated copolymer on the hydroxyapatite (HA) surface is proposed to significantly improve the adsorption stability and thus enhance the biofunction durability accordingly. The phosphoryl (-PO3) grafted branch is employed in the functional polymer to facilitate attaching to the HA substrate. In addition, the polymer integrates the nonfouling polymer brushes of poly(ethylene glycol) (PEG) with the cell-adhesive moiety of cyclic Arg-Gly-Asp-d-Phe-Cys peptides (cRGD). A systematic study on the as-synthesized PEGylated graft copolymer indicates a synergistic binding mechanism of the NH2 and PO3 groups to HA, achieving a high surface coverage with desirable adsorption stability. The cRGD/PEGylated copolymers of optimized grafting architecture are proven to effectively adsorb to HA surfaces as a self-assembled copolymer monolayer, showing stability with minimal desorption even in a complex, physiological medium and effectively preventing nonspecific protein adsorption as examined with X-ray photoelectron spectroscopy (XPS) and a quartz crystal microbalance with dissipation (QCM-D). Direct adhesion assays further confirm that the enhanced coating stability and biofunction durability of the phosphonate-grafted, cRGD-PEGylated copolymer can considerably promote osteoblast attachment on HA surfaces, meanwhile preventing microbial adhesion. This research has resulted in a solution of self-assembly polymer structure optimization that exhibits stable nonfouling characteristics.

Preparation and characterization of multi-target nanoparticles for co-drug delivery

Self-assembly of various amphipathic copolymers is a simple method that allows the preparation of complex nanoparticles with several useful properties. Therefore, the aim of this research was to develop nanoparticles with better biocompatibility, biodegradability, and prolonged circulation time in the bloodstream to deliver drugs and genes into breast cancer tissues in a controlled and targeted manner. In this study, the copolymers PLA-chitosan- PEG -folic acid (COPA), PLA-chitosan- PEG -glucose (COPB), COPA & COPB (COPAB) and chitosan- PLA-PEG FA /Glu/VEGF/siRNA/PTX (NPsAB/siRNA/Paclitaxel) were synthesized, to control the release of paclitaxel (PTX) and siRNA and the circulation time of nanoparticles in blood. This was confirmed by 1H NMR and FTIR spectroscopy. The particle size, zeta potential and morphology of NPsAB /siRNA/PTX were studied by DLS and TEM, respectively. The results showed that the NPsAB/siRNA/PTX had spherical morphology with particle size and zeta potential about 200 nm and −7.8 mV, respectively. In vitro cytotoxicity assay results showed that the nanoparticles had good biocompatibility and low toxicity. Also demonstrated that NPsAB in the serum medium improved the efficiency of drug and siRNA delivery more than two-fold compared to COPA, COPB, and COPAB nanoparticles. Due to results the release pattern of siRNA and PTX from NPsAB nanoparticles under an acidic environment was significantly higher than that of their release rate in a neutral medium. Therefore, due to the acidity of tumor tissue, this property of NPsAB nanoparticles seems to be useful in the treatment of cancer.

Cross-domain Chirality Transfer in Self-Assembly of Chiral Block Copolymers.

Chirality transfer is essential to acquire helical hierarchical superstructures from the self-assembly of supramolecular materials. By taking advantage of chirality transfers at different length scales through intra-chain and inter-chain chiral interactions, helical phase (H*) can be formed from the self-assembly of chiral block copolymers (BCPs*). In this study, chiral triblock terpolymers, polystyrene-b-poly(ethylene oxide)-b-poly(L-lactide) (PS-PEO-PLLA), and polystyrene-b-poly(4-vinylpyridine)-b-poly(L-lactide) (PS-P4VP-PLLA) are synthesized for self-assembly. For PS-PEO-PLLA with an achiral PEO mid-block that is compatible with PLLA (chiral end-block), H* can be formed while the block length is below a critical value. By contrast, for the one with achiral P4VP mid-block that is incompatible with PLLA, the formation of H* phase would be suppressed regardless of the length of the mid-block, giving cylinder phase. Those results elucidate a new type of chirality transfer across the phase domain that is referred as cross-domain chirality transfer, providing complementary understanding of the chirality transfer at the interface of phase-separated domains.

Degradable Block Copolymer Nanoparticles Synthesized by Polymerization-Induced Self-Assembly.

Polymerization-induced self-assembly (PISA) combines polymerization and in situ self-assembly of block copolymers in one system and has become a widely used method to prepare block copolymer nanoparticles at high concentrations. The persistence of polymers in the environment poses a huge threat to the ecosystem and represents a significant waste of resources. There is an urgent need to develop novel chemical approaches to synthesize degradable polymers. To meet with this demand, it is crucial to install degradability into PISA nanoparticles. Most recently, degradable PISA nanoparticles have been synthesized by introducing degradation mechanisms into either shell-forming or core-forming blocks. This Minireview summarizes the development in degradable block copolymer nanoparticles synthesized by PISA, including shell-degradable, core-degradable, and all-degradable nanoparticles. Future development will benefit from expansion of polymerization techniques with new degradation mechanisms and adaptation of high-throughput approaches for both PISA syntheses and degradation studies.

Molecular Design and Controlled Self-Assembly of Copolymers as Core-Shell-Corona Nanoparticles for Smarter Tumor Treatment.

Copolymer-based core-shell-corona nanoparticles have attracted more interest for tumor chemotherapy, owing to their unique multifunctionality benefiting from their unique multilevel topological structure in comparison with the conventional core-shell ones. Here, the recent progress in such core-shell-corona nanoparticle-based drug delivery systems (DDSs) in tumor chemotherapy was reviewed, focusing on additive functionality of the shell layer for controlled drug release performance from the viewpoints of the molecular design and controlled self-assembly, such as stimuli-responsive gatekeepers, independent loading of active substances, and so on. Moreover, future perspectives have been prospected for smarter tumor treatment.

Thermal, pH, and Photo Multistimuli Responsive Block Copolymer Self-Assembly Nanoparticles for Drug Delivery Using Visible-Light-Induced PET-RAFT

Thermal, pH, and Photo Multistimuli Responsive Block Copolymer Self-Assembly Nanoparticles for Drug Delivery Using Visible-Light-Induced PET-RAFT

Preparation and mechanical properties of epoxy resin filled with shaped hybrid nanobrushes

Nanostructure formed through self-assembly of block copolymer has been used to modify epoxy resins and the shape of the nanobrushes has a significant effect on its properties. Through RAFT polymerization and bulk self-assembly of PMMA-b-PTEPM block copolymers, SiO2@PMMA hybrid nanobrushes was prepared with three different shapes, i.e., nanospheres, nanowires and nanosheets. According to the transmission electron microscope results, all three kinds of nanobrushes were well dispersed in the epoxy resins. The differential scanning calorimeter and thermogravimetric analysis tests showed that the addition of these nanobrushes has no significate effect on the curing behaviour and the glass transition temperature of epoxy resins. Their modification effects have been investigated through tensile, bending and impact tests. Compared with the neat epoxy resin, the bending and tensile strengths of 0.5 wt% nanosphere-filled epoxy resins were increased by 11.7% and 27.0%, and the impact strength of 0.5 wt% nanowire-modified epoxy resins was increased by 93.0%. And the nanosphere-modified epoxy resins showed a better comprehensive performance.

Synthesis and self-assembly of dendritic-linear block copolymers containing poly(mandelic acid) with discrete molecular weights and stereochemical structures.

In this work, we present the synthesis of uniform PMAs, where the number of repeat units and their stereochemical arrangement are precisely defined. Utilizing an iterative convergent approach with orthogonally protected dimandelic acid building blocks, we achieved high molecular weight PMAs with the desired number of repeat units, extending up to 144 mandelic acids. Additionally, stereochemically defined poly(l-mandelic acid)s with up to 32 repeat units were successfully synthesized. These uniform PMAs were subsequently coupled with uniform branched poly(ethylene glycol) blocks to create uniform dendritic-linear block copolymers. The self-assembly of these block copolymers in solution was systematically investigated. In solution self-assembly, the synthesized block copolymers showed multiple phases from cylinder to inverse cubic as the molecular weight of PMA increased. In the case of solvent diffusion-evaporation-mediated self-assembly, the block copolymers underwent a phase transition as the rate of water addition decreased.

PH-controlled breakup of fractal aggregates, microgels and gels formed by self-assembled amphiphilic triblock copolymers.

The degradation of (micro)gels and fractal aggregates based on self-assembled amphiphilic triblock copolymers has been investigated in water by confocal microscopy and light scattering respectively. The triblock copolymer consisted of a central hydrophilic poly(acrylic acid) (pAA) block and two hydrophobic end blocks that contained an equal amount of randomly distributed n-butyl acrylate (nBA) and AA units. These latter units helped at tempering the hydrophobic end blocks resulting in the control and the fine tuning of the dynamics of the self-assembled triblock through the pH. Starting from a pH where the dynamics is frozen, the rate of breakup of the macroscopic gels, microgels and of fractal aggregates was measured after increasing the pH to different values. The mechanism of the breakup was found to be independent of the pH, but its rate increased exponentially with increasing pH. The degradation proceeded through the release of the polymers from the bulk into the surrounding aqueous phase.

Self-assembly of rod-coil-rod block copolymers in a coil-selective solvent: coarse-grained simulation results.

The solution self-assembly of amphiphilic polymers provides a versatile approach to design novel nanostructured materials. Multiblock polymers, particularly those composed of liquid crystalline and coil blocks, are of significant interest due to the potential display of nematic ordering in liquid crystalline domains, offering intriguing optical and mechanical properties. In this study, dissipative particle dynamics is used to investigate the solution self-assembly of rod-coil-rod copolymers in a coil-selective solvent. Extensive molecular simulations were conducted to elucidate the impact of polymer composition, concentration and flexibility on the self-assembly behavior. A quantitative analysis was performed to investigate how polymer conformations varied with changes in composition, concentration, and rigidity. Simulation results show that, at small rod compositions, rod-coil-rod polymers self-assemble into micelles at low concentrations, transitioning to network formation as concentration increases. An increase in rod composition leads to the formation of larger aggregates, resulting in cylindrical micelles and membranes. The results reported here also offer insights into the role of flexibility in shaping the self-assembly behavior of rod-coil-rod triblocks in selective solvents, thus, contributing to a comprehensive understanding of the factors governing the formation of diverse structures in the solution self-assembly of triblock copolymers.

The mechanism underlying the transitions between stripes, helices, and stacked toroids in the cylindrical shell formed by AB diblock copolymers on a long nanocylinder.

The self-assembly of block copolymers on nanocylinders has attracted a lot of interest due to its potential application in biomedicine and other fields. In this study, the self-assembly phase behavior of AB diblock copolymers on long nanocylinders in soft confinement has been studied by using a simulated annealing method. A square phase diagram of the morphology was constructed by increasing the number of chains of copolymers (cn) and the cylindrical diameter (D). As a result, morphological transitions from striped to helical and axially stacked toroids, as well as reversible transitions, started to appear. By analyzing the chain packing in a fan-shaped region and calculating the mean-square end-to-end distance (DEE2) of the copolymers and number of AB contacts, both types of transitions were found to be driven by the competition between conformational entropy and AB interfacial energy. The number of stripes increased and the helical angle decreased with the increase in cylinder diameter. The chirality of the helix was found to be random.

Structure, humidity adaptivity, and elasticity of hydrogen-bonded complexes formed by self-assembly of a triblock copolymer and a homopolymer

The tri-block copolymer polystyrene-b-poly(ethylene oxide)-b-polystyrene (SES) and the homopolymer poly(acrylic acid) (PAA) were applied to fabricate elastomers with multi-hierarchical architectures.

Self-assembly of amphiphilic asymmetric comb-like copolymers with responsive rigid side chains.

Amphiphilic asymmetric comb-like copolymers (AACCs) exhibit distinct self-assembly behaviours due to their unique architecture. However, the synthetic difficulties of well-defined AACCs have prohibited a systematic understanding of the architecture-morphology relationship. In this work, we conducted dissipative particle dynamics simulations to investigate the self-assembly behaviours of AACCs with responsive rigid side chains in selective solvents. The effects of side chain length, number of branches, and spacers on the morphology of aggregates were investigated by mapping out morphology diagrams. Besides, the numbers and surface areas of aggregates clearly depicted the morphological transitions during the self-assembly process. Moreover, the rod-to-coil conformation transitions were simulated to explore the stimuli-responsive behaviour of the AACCs with responsive rigid side chains by adjusting the bond angle parameter of the rigid chains. The results indicated that without the support of the rigid chains, the assembly structure collapsed, leading to the tube-to-channelized micelles and one-compartment-to-multicompartment vesicle morphology transformations. The simulation results are consistent with earlier experimental results, which can provide theoretical guidance for assembly toward desired nanostructures.

Macromolecular architectural effects on solution self-assembly of amphiphilic AB-type block copolymers

This review discusses the self-assembly of amphiphilic linear and various non-linear polymers such as star and cyclic architectures, highlighting how polymer architecture impacts self-assembly behavior.