Chain Exchange Research Articles

Synthesis and Characterization of Lipid-Polyzwitterion Diblock Copolymers for Optimizing Micelle Formation to Enhance Anticancer Drug Delivery in 2D and 3D Cell Cultures.

Amphiphilic polymers with distinct polarity differences, known as sharp polarity contrast polymers (SPCPs), have gained much attention for their ability to form micelles with low critical micelle concentrations (CMCs) and potential in anticancer drug delivery. This study addresses the limited research on structure-property relationships of SPCPs by developing various SPCPs and exploring their physicochemical properties and biological applications. Specifically, the superhydrophobic aliphatic palmitoyl (Pal) was coupled to the superhydrophilic zwitterionic poly(2-methacryloyloxyethyl phosphorylcholine) (pMPC) to form Pal-pMPC diblock copolymers. Adjusting the lengths of hydrophilic chains allowed the creation of structures with varying hydrophilic-hydrophobic ratios for micelle formation. Comprehensive evaluations were carried out, including particle size, CMC, chain exchange rates, cellular uptake efficiency, and anticancer effectiveness. Our findings indicate that micelles with optimal hydrophilic-hydrophobic ratios significantly enhanced cellular uptake and cytotoxicity in both two-dimensional (2D) and three-dimensional (3D) tumor models, offering valuable insights for designing SPCPs for anticancer drug delivery.

Effect of polymer architecture on the properties and in vitro cytotoxicity of drug formulation: A case study with mono- and di-gradient amphiphilic poly(2-Oxazoline)s.

Due to the straightforward single-step synthesis, amphiphilic gradient copoly(2-oxazoline)s are becoming more popular alternative to their block analogue for the development of next-generation drug delivery systems. Here, we investigated the influence of polymer architecture on the physiochemical and biological assessment of nanoformulations formed by the self-assembly of gradient copoly(2-oxazoline)s. Two different architectures were synthesized: hydrophilic-grad-hydrophobic (mono-gradient) and hydrophobic-grad-hydrophilic-grad-hydrophobic (di-gradient) which contained a hydrophilic monomer, 2-ethyl-2-oxazoline (EtOx) and a hydrophobic monomer, 2-phenyl-2-oxazoline (PhOx). Di-gradient copolymers self-assembled in the presence of a hydrophobic model drug, curcumin and formed monodispersed or slightly polydispersed nanoparticle solution. On the other hand, mono-gradient copolymers formed polydispersed nanoparticle solutions. Di-gradient copolymer was slightly more efficient to solubilize curcumin. Mono-gradient copolymer nanoparticle showed faster monomer chain exchange kinetics and comparatively less stability in the presence of serum albumin. At longer incubation times, faster drug release was observed from the mono-gradient copolymer nanoformulations. Cytotoxicity of free curcumin and curcumin loaded nanoparticles in cancer cell of U87 MG (human glioblastoma cell) was dose and time-dependent, whereby the significant cell death occurred after 48 h. Curcumin-loaded mono-gradient copolymer nanoparticles inhibited U87MG cancel cell growth to a large extent compared to the di-gradient copolymer nanoparticles.

Generation of binder-format-payload conjugate-matrices by antibody chain-exchange

The generation of antibody-drug conjugates with optimal functionality depends on many parameters. These include binder epitope, antibody format, linker composition, conjugation site(s), drug-to-antibody ratio, and conjugation method. The production of matrices that cover all possible parameters is a major challenge in identifying optimal antibody-drug conjugates. To address this bottleneck, we adapted our Format Chain Exchange technology (FORCE), originally established for bispecific antibodies, toward the generation of binder-format-payload matrices (pair-FORCE). Antibody derivatives with exchange-enabled Fc-heterodimers are combined with payload-conjugated Fc donors, and subsequent chain-exchange transfers payloads to antibody derivatives in different formats. The resulting binder-format-conjugate matrices can be generated with cytotoxic payloads, dyes, haptens, and large molecules, resulting in versatile tools for ADC screening campaigns. We show the relevance of pair-FORCE for identifying optimal HER2-targeting antibody-drug conjugates. Analysis of this matrix reveals that the notion of format-defines-function applies not only to bispecific antibodies, but also to antibody-drug conjugates.

Kinetics of Chain Exchange in Asymmetric ABA′ Triblock Polymer Micelles by Time-Resolved Small-Angle Neutron Scattering

Kinetics of Chain Exchange in Asymmetric ABA′ Triblock Polymer Micelles by Time-Resolved Small-Angle Neutron Scattering

Multicomponent Self-Assembly and Self-Sorting of Polymer Micelles in Water: Selective and Switchable Association by Kinetic or Thermodynamic Control.

Herein, we report multicomponent self-assembly and self-sorting of polymer micelles in water using mixtures of an anionic random copolymer bearing sodium sulfonate and dodecyl groups and random copolymers carrying poly(ethylene glycol) (PEG) and alkyl groups. In pure water, the anionic copolymer is co-self-assembled with the PEG copolymers to form anion/PEG-fused micelles with a controlled aggregation number. By designing the composition or alkyl groups of PEG copolymers, the fused micelle is reversibly self-sorted into discrete anion or PEG micelles in the presence of NaCl. Co-self-assembly of the anionic copolymer and PEG copolymers is kinetically or thermodynamically controlled, depending on the dynamic properties of the PEG copolymer micelles. Thus, the selective self-assembly of ternary copolymers is also controllable and switchable by temperature: A kinetically favored anion/PEG-fused micelle is predominantly formed in the presence of a kinetically frozen PEG micelle at low temperature, whereas the fused micelle is transformed via polymer chain exchange upon heating into a thermodynamically more stable anion/PEG-fused micelle.

Interfacial exchange dynamics of biomolecular condensates are highly sensitive to client interactions.

Phase separation of biomolecules can facilitate their spatiotemporally regulated self-assembly within living cells. Due to the selective yet dynamic exchange of biomolecules across condensate interfaces, condensates can function as reactive hubs by concentrating enzymatic components for faster kinetics. The principles governing this dynamic exchange between condensate phases, however, are poorly understood. In this work, we systematically investigate the influence of client-sticker interactions on the exchange dynamics of protein molecules across condensate interfaces. We show that increasing affinity between a model protein scaffold and its client molecules causes the exchange of protein chains between the dilute and dense phases to slow down and that beyond a threshold interaction strength, this slowdown in exchange becomes substantial. Investigating the impact of interaction symmetry, we found that chain exchange dynamics are also considerably slower when client molecules interact equally with different sticky residues in the protein. The slowdown of exchange is due to a sequestration effect, by which there are fewer unbound stickers available at the interface to which dilute phase chains may attach. These findings highlight the fundamental connection between client-scaffold interaction networks and condensate exchange dynamics.

A visualizable strategy to real-time monitor chiral block copolypeptide assembly by AIE fluorescent probes

Aggregation-induced emission (AIE) luminogens show great potential in many applications. In this study, we have synthesized diblock copolymers poly (ethylene glycol) -b-poly (9-anthrylmethyl-L-lysine) (PEG-b-PLLys-An) and poly (ethylene glycol) -b-poly (9-anthrylmethyl-D-lysine) PEG-b-PDLys-An with opposite handedness by ring-opening polymerization and post-modification. Both diblock copolymers can self-assemble into spherical micelles or planar connected disc-like aggregates at different water fractions. In addition, the copolymers present a typical AIE process concomitant with the self-assembly process. To facilitate the study of chain exchange kinetics, we develope a novel visualizable strategy based on fluorescence variation. This strategy allows us to monitor the real-time chain exchange process by mixing equimolar solutions of PEG44-b-PDLys20-An and PEG44-b-PLLys20-An with varying water volume fractions. We indicate that chain exchange predominantly occurs at low water fractions through a single-molecule extraction and redistribution mechanism rather than micellar fission and fusion. In contrast, the micelles appear to be "kinetically frozen" at high water fractions, suggesting suppressed chain exchange under these conditions. Importantly, our approach offers a visually observable method for probing the dynamics of micellar chain exchange in real time.

Correction to “Bimodal Rates for Cavitation-Induced Chain Exchange between Micelles”

Correction to “Bimodal Rates for Cavitation-Induced Chain Exchange between Micelles”

PLA reinforced with modified chokeberry pomace and beetroot pulp fillers. Effect of oligomeric chain extender on the properties of biocomposites

Agri-food waste is an exciting way to use as a polymer filler. It is an ecological option for cutting down the material cost, especially relatively expensive biodegradable plastics. In this paper, lignocellulosic residues of chokeberry pomace (CP) and beetroot pulp (BP) are grafted with lactic acid oligomers (OLAs) in direct condensation of lactic acid (LAc) into the lignocellulosic backbone. Biocomposites with modified and unmodified fillers were prepared using poly (lactic acid) (PLA) matrix. Additionally, the influence of an epoxy-based chain extender (Joncryl® ADR 4468 (ADR)) on the properties of the biocomposites mentioned above was checked. SEM was used for the characterisation of modified and unmodified fillers. The success of the grafting reaction was confirmed by FTIR and 1HNMR analyses. DSC, DMA and TGA was applied for the characterisation of thermal properties of produced biocomposites. The influence of chemical modification and introduction of ADR to the biocomposite on water absorption, rheological and mechanical properties were tested. Moreover, the reaction between ADR and the lignocellulosic backbone of the CP filler was studied by FTIR analysis. Results showed, that modification of the filler using OLAs has a significant influence on reducing water absorption by 48.3 and 56.5 % for CP and BP biocomposites, respectively. The tensile strength increased after the modification and introduction of ADR. The chemical treatment of the filler causes an increase in the tensile strength by about 29 and 8 % compared to unmodified CP and BP fillers, respectively. 0.75 % of ADR in CP/PLA biocomposite allowed for an increase in tensile strength by 51 %. Rheological study showed that presence of ADR compensates the consequences of hydrolysis and segment exchange of the PLA chains caused by water and OLAs, respectively. Results are promising for the production of ecological biocomposites with satisfying mechanical, thermal and rheological properties compared to biocomposites with unmodified lignocellulosic filler.

Unraveling Chain Exchange Kinetics in Mixed Micelles through FRET: Impact of Segment Interactions between Hydrophilic Polymers in the Corona

Unraveling Chain Exchange Kinetics in Mixed Micelles through FRET: Impact of Segment Interactions between Hydrophilic Polymers in the Corona

Stereocomplex-Driven Morphological Transition of Coil-Rod-Coil Poly(lactic acid)-Based Cylindrical Nanoparticles.

The stereocomplexation of poly(lactic acid) (PLA) enantiomers opens up an avenue for the formation of new materials with enhanced performance, specifically regarding their mechanical and thermal resistance and resistance to hydrolysis. Despite these useful features, the study of the stereocomplexation between block copolymers based on PLA in solution is limited, and a comprehensive understanding of this phenomenon is urgently needed. Herein, triblock copolymers of poly(N-hydroxyethyl acrylamide) and PL(or D)LA in which PLA was midblock (PHEAAmy-b-PL(D)LAx-b-PHEAAmy) were synthesized and assembled into cylindrical micelles via crystallization-driven self-assembly . The stereocomplexation between enantiomeric micelles facilitates the morphological transition, and the transformation process was investigated in detail by varying the aging temperature, block composition, and solvent. It was found that the solubility of the copolymers played a vital role in determining the occurrence and the speed of the chain exchange between the micelles and the unimers, which thereafter has a significant impact on the shape transition. These results lead to a deeper understanding of the stereocomplex-driven morphological transition process and provide valuable guidance for further optimization of the transition under physiological conditions as a new category of stimuli-responsive systems for biomedical applications.

Modeling Viscoelasticity and Dynamic Nematic Order of Exchangeable Liquid Crystal Elastomers.

Exchangeable liquid crystal elastomers (XLCEs), an emerging class of recyclable polymer materials, consist of liquid crystalline polymers which are dynamically crosslinked. We develop a macroscopic continuum model by incorporating the microscopic dynamic features of the cross-links, which can be utilized to understand the viscoelasticity of the materials together with the dynamic nematic order. As applications of the model, we study the rheological responses of XLCEs in three cases: stress relaxation, strain ramp, and creep compliance, where the materials show interesting rheology as an interplay between the dynamic nematic order of the mesogenic units, the elasticity from the network structure, and the dissipation due to chain exchange reactions. Not only being useful in understanding the physical mechanism underlying the fascinating characteristics of XLCEs, this work can also guide their future fabrications with desired rheological properties.

Multiple Dynamic Bonds-Driven Integrated Cathode/Polymer Electrolyte for Stable All-Solid-State Lithium Metal Batteries.

All-solid-state lithium metal batteries (LMBs) are considered as the promising higher-energy and improved-safety energy-storage systems. Nevertheless, the electrolyte-electrodes interfacial issues due to the limited solid physical contact lead to discontinuous interfacial charge transport and large interfacial resistance, thereby suffering from unsatisfactory electrochemical performance. Herein, we construct an integrated cathode/polymer electrolyte for all-solid-state LMBs under the action of polymer chains exchange and recombination originating from multiple dynamic bonds in our well-designed dynamic supramolecular ionic conductive elastomers (DSICE) molecular structure. The DSICE acts as polymer electrolytes with excellent electrochemical performance and mechanical properties, achieving the ultrathin pure polymer electrolyte thickness (12 μm). Notably, the DSICE also functions as lithium iron phosphate (LiFePO4, LFP) cathode binders with enhanced adhesive capability. Such well-constructed Li|DSICE|LFP-DSICE cells generate delicate electrolyte-electrodes interfacial contact at the molecular level, providing continuous Li+ transport pathways and promoting uniform Li+ deposition, further delivering superior long-term charge/discharge stability (>600 cycles, Coulombic efficiency, >99.8%) and high capacity retention (80% after 400 cycles). More practically, the Li|DSICE|LFP-DSICE pouch cells show stable electrochemical performance, excellent flexibility and safety under abusive tests.

Multiple Dynamic Bonds‐Driven Integrated Cathode/Polymer Electrolyte for Stable All‐Solid‐State Lithium Metal Batteries

AbstractAll‐solid‐state lithium metal batteries (LMBs) are considered as the promising higher‐energy and improved‐safety energy‐storage systems. Nevertheless, the electrolyte‐electrodes interfacial issues due to the limited solid physical contact lead to discontinuous interfacial charge transport and large interfacial resistance, thereby suffering from unsatisfactory electrochemical performance. Herein, we construct an integrated cathode/polymer electrolyte for all‐solid‐state LMBs under the action of polymer chains exchange and recombination originating from multiple dynamic bonds in our well‐designed dynamic supramolecular ionic conductive elastomers (DSICE) molecular structure. The DSICE acts as polymer electrolytes with excellent electrochemical performance and mechanical properties, achieving the ultrathin pure polymer electrolyte thickness (12 μm). Notably, the DSICE also functions as lithium iron phosphate (LiFePO4, LFP) cathode binders with enhanced adhesive capability. Such well‐constructed Li|DSICE|LFP‐DSICE cells generate delicate electrolyte‐electrodes interfacial contact at the molecular level, providing continuous Li+ transport pathways and promoting uniform Li+ deposition, further delivering superior long‐term charge/discharge stability (>600 cycles, Coulombic efficiency, >99.8 %) and high capacity retention (80 % after 400 cycles). More practically, the Li|DSICE|LFP‐DSICE pouch cells show stable electrochemical performance, excellent flexibility and safety under abusive tests.

FRET-based analysis on the structural stability of polymeric micelles: Another key attribute beyond PEG coverage and particle size affecting the blood clearance

Various attributes of micelles, such as PEG density and particle size, are considered to be related to blood clearance. The structural stability of micelles is another key attribute that will affect the in vivo fate. This study employed fluorescence resonance energy transfer (FRET) analysis to guide the preparation of polymeric micelles with different structural stability. Micelles prepared using copolymers with longer hydrophobic blocks showed higher structural stability; emulsification was a better method than nanoprecipitation to prepare stable micelles. The fast chain exchange kinetics and the high-water content of micellar cores explained the low structural stability of those micelles. Moreover, this study highlighted the importance of structural stability that affected blood clearance in concert with PEG length and particle size. One-third of the small and stable micelles were detected in the blood 24 h after injection. While unstable micelles would be cleared from the circulation within 4 h. Notably, there would be a threshold of structural stability. Micelles with structural stability below this threshold were quickly cleared even if they possessed a longer PEG length and a smaller size. In contrast, higher structural stability allowed polymeric micelles to maintain higher integrity in vivo and enhance tumor accumulation and anti-tumor efficacy. In conclusion, this study systematically analyzed the importance of the structural stability of micelles on the in vivo fate.

Recent Advances in Polymerization‐Induced Self‐Assembly (PISA) Syntheses in Non‐Polar Media

AbstractIt is well‐known that polymerization‐induced self‐assembly (PISA) is a powerful and highly versatile technique for the rational synthesis of colloidal dispersions of diblock copolymer nanoparticles, including spheres, worms or vesicles. PISA can be conducted in water, polar solvents or non‐polar media. In principle, the latter formulations offer a wide range of potential commercial applications. However, there has been just one review focused on PISA syntheses in non‐polar media and this prior article was published in 2016. The purpose of the current review article is to summarize the various advances that have been reported since then. In particular, PISA syntheses conducted using reversible addition‐fragmentation chain‐transfer (RAFT) polymerization in various n‐alkanes, poly(α‐olefins), mineral oil, low‐viscosity silicone oils or supercritical CO2 are discussed in detail. Selected formulations exhibit thermally induced worm‐to‐sphere or vesicle‐to‐worm morphological transitions and the rheological properties of various examples of worm gels in non‐polar media are summarized. Finally, visible absorption spectroscopy and small‐angle X‐ray scattering (SAXS) enable in situ monitoring of nanoparticle formation, while small‐angle neutron scattering (SANS) can be used to examine micelle fusion/fission and chain exchange mechanisms.

Recent Advances in Polymerization-Induced Self-Assembly (PISA) Syntheses in Non-Polar Media.

It is well-known that polymerization-induced self-assembly (PISA) is a powerful and highly versatile technique for the rational synthesis of colloidal dispersions of diblock copolymer nanoparticles, including spheres, worms or vesicles. PISA can be conducted in water, polar solvents or non-polar media. In principle, the latter formulations offer a wide range of potential commercial applications. However, there has been just one review focused on PISA syntheses in non-polar media and this prior article was published in 2016. The purpose of the current review article is to summarize the various advances that have been reported since then. In particular, PISA syntheses conducted using reversible addition-fragmentation chain-transfer (RAFT) polymerization in various n-alkanes, poly(α-olefins), mineral oil, low-viscosity silicone oils or supercritical CO2 are discussed in detail. Selected formulations exhibit thermally induced worm-to-sphere or vesicle-to-worm morphological transitions and the rheological properties of various examples of worm gels in non-polar media are summarized. Finally, visible absorption spectroscopy and small-angle X-ray scattering (SAXS) enable in situ monitoring of nanoparticle formation, while small-angle neutron scattering (SANS) can be used to examine micelle fusion/fission and chain exchange mechanisms.

Loosely Adsorbed Chains Expedite the Desorption of Flattened Polystyrene Chains on Flat Silicon Surface.

Herein, the desorption of the adsorbed chains (including two regions of flattened chains and loosely adsorbed chains) was examined by monitoring the chain exchange kinetics between the adsorbed chains and the top-free chains in a bilayer system by using fluorine-labeled polystyrene (PS). The results indicated that the exchange behavior of PS-flattened chains with the top-free chains is much slower than that of PS-loose chains and has a strong molecular weight (MW) dependence. Interestingly, in the presence of loosely adsorbed chains, the desorption of flattened chains was accelerated greatly and had weaker MW dependency. We attribute the MW-dependent desorption phenomena to the average number of contact sites between polymer adsorbed chains and the substrate, which rapidly increased with increasing MW. Likewise, the desorption of loosely adsorbed chains may provide extra conformational energy to accelerate the desorption of flattened chains.

Polyester-based epoxy vitrimer integrating spent coffee ground as a natural filler

Coffee is a widely consumed beverage, but approximately 80% mass of coffee cherry is discarded as waste. In this study, spent coffee grounds (SCG) were recycled and used as a natural filler in a polyester-based epoxy matrix made from reactions of diglycidyl ethers of Bisphenol A and polyethylene glycol with methyl nadic anhydride. The properties of SCG/epoxy composites with various SCG contents up to 40% w/w were evaluated using various techniques such as FT-IR spectroscopy, tensile testing, optical microscopy, differential scanning calorimetry, and rheology. The SCG filled polyester-based epoxy matrix demonstrated excellent dimensional stability and retained a permanently crosslinked network, but re-shaping was possible at ∼150 °C through transesterification, which occurred due to a dynamic chain exchange reaction between the ester group of the epoxy matrix and the hydroxyl group of the SCG fillers. The transesterification also improved the interfacial adhesion between the matrix and SCG fillers, resulting in tensile strength of over 20 MPa and a modulus of around 2.5 GPa, even with high SCG contents up to 40% w/w. While neat, cured epoxy shows thermoset behavior, filling the matrix with SCG enables reforming and origami-inspired spontaneous change in shape.

Dynamic Exchange of Amphiphilic Random Copolymers between Micelles in Water: Kinetics and Mechanism Analyzed by TR-SANS

Amphiphilic random copolymers bearing poly(ethylene glycol) (PEG) and alkyl groups as side chains are intermolecularly self-assembled into size-controlled multichain micelles in water. The random copolymer micelles are known to induce the exchange of their polymer chains, whereas the details of the kinetics and mechanism have not been elucidated yet. Herein, we investigated the exchange kinetics and mechanism of the random copolymer chains between their micelles by time-resolved small-angle neutron scattering (TR-SANS). For this purpose, random copolymers carrying PEG and deuterated butyl or dodecyl groups were designed for deuterated micelles. After mixing deuterated and non-deuterated micelle solutions, the resulting mixtures were monitored by TR-SANS at various concentrations and temperatures. The scattering intensity of the micelle mixtures decayed with time, indicating that deuterated copolymers were gradually mixed with non-deuterated copolymers via chain exchange between their micelles to form micelles consisting of both deuterated and non-deuterated copolymers. The kinetic analysis revealed that the exchange of their polymer chains involved two mechanisms: A unimer release and insertion pathway was dominant in diluted conditions, whereas the contribution of a micelle collision pathway increased with increasing total polymer concentration and temperature. The activation energy of the polymer exchange process was dependent on the hydrophobic alkyl groups and larger than that of a related surfactant micelle.