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Cell therapies such as CAR−T have demonstrated significant clinical successes, driving the investigation of immune cell surface engineering using natural and synthetic materials to enhance their therapeutic performance. However, many of these materials do not fully replicate the dynamic nature of the extracellular matrix (ECM). This study presents a cell surface engineering strategy that utilizes phase‐separated peptide coacervates to decorate the surface of immune cells. We meticulously designed a tripeptide, Fmoc−Lys−Gly−Dopa−OH (KGdelta; Fmoc=fluorenylmethyloxycarbonyl; delta=Dopa, dihydroxyphenylalanine), that forms coacervates in aqueous solution via phase separation. These coacervates, mirroring the phase separation properties of ECM proteins, coat the natural killer (NK) cell surface with the assistance of Fe3+ ions and create an outer layer capable of encapsulating monoclonal antibodies (mAb), such as Trastuzumab. The antibody‐embedded coacervate layer equips the NK cells with the ability to recognize cancer cells and eliminate them through enhanced antibody‐dependent cellular cytotoxicity (ADCC). This work thus presents a unique strategy of cell surface functionalization and demonstrates its use in displaying cancer‐targeting mAb for cancer therapies, highlighting its potential application in the field of cancer therapy. [ABSTRACT FROM AUTHOR]

Adhesives can intimately connect humans to machines, seamlessly bond diverse tissues in the human body, and manage various diseases. However, the precise spatial control of wet and tough adhesion of biocompatible hydrogels on biological tissues remains a major challenge. Inspired by the bioglue secreted by sandcastle worms, the design of printable tough adhesives (PTAs) is proposed, a supramolecular hydrogel that can be printed into defined structures, in situ mechanically reinforced into a tough matrix with physiologically relevant benign triggers, and strongly adhere to diverse substrates. With carefully selected polymer components and ratios, it is discovered that the 3D printed PTAs can achieve a marked increase in toughness, tensile strength, and stiffness after being immersed in water/saline solution or attached to biological tissues. To assess the robust toughening mechanism triggered by the supramolecular interactions, the effects of polymer content and pH on the mechanical performance of PTAs and the kinetics of their triggered reinforcement are thoroughly investigated. The potential of PTAs is further demonstrated for manufacturing tough connective tissue mimetics, controlling patterned bioadhesion, and designing programmable 4D soft robotics. The bioinspired, printable, benignly triggerable, and adhesive supramolecular PTAs are expected to find broad applications in engineering and medicine. [ABSTRACT FROM AUTHOR]

Pea proteins are widely used as a food ingredient, especially in sustainable food formulations. The seed itself consists of many proteins with different structures and properties that determine their structure-forming properties in food matrices, such as emulsions, foams, and gels. This review discusses the current insights into the structuring properties of pea protein mixtures (concentrates, isolates) and the resulting individual fractions (globulins, albumins). The structural molecular features of the proteins found in pea seeds are discussed and based on this information, different structural length scales relevant to foods are reviewed. The main finding of this article is that the different pea proteins are able to form and stabilize structural components found in foods such as air-water and oil-water interfaces, gels, and anisotropic structures. Current research reveals that each individual protein fraction has unique structure-forming properties and that tailored breeding and fractionation processes will be required to optimize these properties. Especially the use of albumins, globulins, and mixed albumin-globulins proved to be useful in specific food structures such as foams, emulsions, and self-coacervation, respectively. These new research findings will transform how pea proteins are processed and being used in novel sustainable food formulations in the future. [ABSTRACT FROM AUTHOR]

The liquid-liquid phase separation of biopolymers in living cells contains multiple interactions and occurs in a dynamic environment. Resolving the regulation mechanism is still a challenge. In this work, we designed a series of peptides (XXLY)6SSSGSS and studied their complexation and coacervation behavior with single-stranded oligonucleotides. The "X" and "Y" are varied to combine known amounts of charged and non-charged amino acids, together with the introduction of secondary structures and pH responsiveness. Results show that the electrostatic interaction, which is described as charge density, controls both the strength of complexation and the degree of chain relaxation, and thus determines the growth and size of the coacervates. The hydrophobic interaction is prominent when the charges are neutralized. Interestingly, the secondary structures of peptides exhibit profound effect on the morphology of the phases, such as solid phase to liquid phase transition. Our study gains insight into the phase separation under physiological conditions. It is also helpful to create coacervates with desirable structures and functions. [ABSTRACT FROM AUTHOR]

[Display omitted] • Temperature affects how C3Ms with PEO shells behave. • Temperature increase produces a transition from spherical to elongated coacervate micelles. • Sphere-to-rod transition of coacervate micelles closely follows the behavior of ethoxylated surfactant micelles. • The packing parameter model for surfactant micelles is also applicable to polymeric C3Ms. Ethoxylated complex coacervate core micelles (C3Ms), formed by the electrostatic coacervation of a charge-neutral diblock copolymer and an oppositely charged homopolymer, exhibit morphology governed by molecular packing principles. Additionally, this morphology is temperature-dependent, leading to transitions similar to those observed in classical ethoxylated surfactant aggregates. To explore the thermal effects on the size and morphology of C3Ms, we employed dynamic light scattering (DLS), small-angle X-ray scattering (SAXS), and cryogenic transmission electron microscopy (cryo-TEM). These techniques were applied to C3Ms formed by copolymers with varying poly(ethylene oxide) (EO) lengths. Increasing the temperature-induced a transition from spherical to elongated aggregates, contingent on the EO block length. This morphological transition in EO-containing C3Ms parallels the behavior of classical ethoxylated surfactant aggregates. Despite the fundamental differences between hydrophobically driven and electrostatic coacervate micelles, our findings suggest that similar molecular packing principles are universally applicable across both systems. Our results offer valuable insights for predicting the structural properties of these coacervate platforms, which is crucial for envisioning their future applications. [ABSTRACT FROM AUTHOR]

Spider dragline silk's exceptional mechanical performance, coupled with its benign production pathway, have inspired the design of diverse smart materials. Remarkably, relatively little is known about the self‐assembly process of major ampullate spidroin 1 (MaSp1) – the main protein constituent of dragline fiber – during its rapid conversion from soluble precursor protein into hierarchically structured mature silk fibers. Herein, the biomimetic potential of MaSp1 is explored using a new recombinant platform with full domain representation. MaSp1 is found to undergo efficient liquid‐liquid phase separation (LLPS) in response to kosmotropic ions, with notably higher propensity compared to MaSp2, and with MaSp1 exhibiting a more complex solubility profile relative to levels of sodium chloride. To further the understanding of silk spinning, the rapid assembly of mesoscale structures is monitored in real‐time in response to ion and pH gradients, revealing a progression from LLPS droplets toward aligned hierarchical fibers. Furthermore, using this biomimetic system, insoluble macroscopic MaSp1 fibers can be readily generated, wherein the application of mechanical deformation triggers the emergence of β‐sheet secondary structures. The insights gained from this study can have broader application in efforts to mimic the formation of biomaterials with spatially organized features across multiple length scales. [ABSTRACT FROM AUTHOR]

Significant progress has been made in wet adhesives for low salinity water, but exploration of general ionic adhesives for natural seawater is less developed because the high salinity could weaken interfacial bonding and shields electrostatic interactions, resulting in adhesion failure. Thus, the design of adhesives for natural seawater represents challenges less resolved. Herein, a cationic polyelectrolyte (PECHIA) containing imidazolacetonitrile unit was explored to prepare adhesives enabled by natural seawater. By combining the ion shielding effect with the "cation-dipole" interactions between PECHIA chains, aqueous solution of the PECHIA underwent coacervation and self-crosslinking in natural seawater, allowing for underwater adhesion to various substrates in seawater. The instantaneous lap-shear and tensile adhesion strengths are 47 and 119 kPa, respectively, while the cured adhesive shows ∼739 kPa tensile adhesion in natural seawater. The design of PECHIA enables wet adhesives viable for applications in the diversified scenarios of natural seawater. [ABSTRACT FROM AUTHOR]

The release of hydrocarbons (HC) into the marine environment has serious consequences, both economically and ecologically. This work presents an efficient process to remove HC pollution from seawater: cloud point extraction (CPE), considered to be a reliable, inexpensive, and environmentally friendly method, using the readily biodegradable nonionic surfactants Lutensol ON30 and Tergitol 15‐S‐7. A real salt water sample with a high chemical oxygen demand (COD = 1700 mg O2/L) was thus treated. First, the phase diagrams of the binary systems (water–surfactant), and the pseudo‐binary systems (water–surfactant–HC), were determined. Second, after a 24 h settling time, considered as optimal, the extraction results, that is, residual soluble COD, residual percentage of surfactant in the dilute phase and volume fraction of coacervate at equilibrium, were expressed in terms of temperature and initial surfactant concentration. For each parameter, the results obtained were modeled using the response surface methodology and represented on three‐dimensional diagrams. They show that the COD can be reduced to 10 and 15 mg O2/L, using Lutensol ON30 and Tergitol 15‐S‐7, respectively, under seawater temperature conditions. Finally, it was shown that the surfactant can be recycled. The present work demonstrates that CPE can reduce the HC content of seawater on a laboratory scale. [ABSTRACT FROM AUTHOR]

Protecting the skin from UV light irradiation in wet and underwater environments is challenging due to the weak adhesion of existing sunscreen materials but highly desired. Herein we report a polyethyleneimine/thioctic acid/titanium dioxide (PEI/TA/TiO2) coacervate-derived hydrogel with robust, asymmetric, and reversible wet bioadhesion and effective UV-light-shielding ability. The PEI/TA/TiO2 complex coacervate can be easily obtained by mixing a PEI solution and TA/TiO2 powder. The fluid PEI/TA/TiO2 coacervate deposited on wet skin can spread into surface irregularities and subsequently transform into a hydrogel with increased cohesion, thereby establishing interdigitated contact and adhesion between the bottom surface and skin. Meanwhile, the functional groups between the skin and hydrogel can form physical interactions to further enhance bioadhesion, whereas the limited movement of amine and carboxyl groups on the top hydrogel surface leads to low adhesion. Therefore, the coacervate-derived hydrogel exhibits asymmetric adhesiveness on the bottom and top surfaces. Moreover, the PEI/TA/TiO2 hydrogel formed on the skin could be easily removed using a NaHCO3 aqueous solution without inflicting damage. More importantly, the PEI/TA/TiO2 hydrogel can function as an effective sunscreen to block UV light and prevent UV-induced MMP-9 overexpression, inflammation, and DNA damage in animal skin. The advantages of PEI/TA/TiO2 coacervate-derived hydrogels include robust, asymmetric, and reversible wet bioadhesion, effective UV light-shielding ability, excellent biocompatibility, and easy preparation and usage, making them a promising bioadhesive to protect the skin from UV light-associated damage in wet and underwater environments.

Living cells are complex, nonequilibrium supramolecular systems capable of independently and/or cooperatively integrating multiple bio‐supramolecules to execute intricate physiological functions that cannot be accomplished by individual biomolecules. These biological design strategies offer valuable insights for the development of synthetic supramolecular systems with spatially controlled hierarchical structures, which, importantly, exhibit cell‐like responses and functions. The next grand challenge in supramolecular chemistry is to control the organization of multiple types of supramolecules in a single system, thus integrating the functions of these supramolecules in an orthogonal and/or cooperative manner. In this perspective, the recent progress in constructing multicomponent supramolecular soft materials through the hybridization of supramolecules, such as self‐assembled nanofibers/gels and coacervates, with other functional molecules, including polymer gels and enzymes is highlighted. Moreover, results show that these materials exhibit bioinspired responses to stimuli, such as bidirectional rheological responses of supramolecular double‐network hydrogels, temporal stimulus pattern‐dependent responses of synthetic coacervates, and 3D hydrogel patterning in response to reaction–diffusion processes are presented. Autonomous active soft materials with cell‐like responses and spatially controlled structures hold promise for diverse applications, including soft robotics with directional motion, point‐of‐care disease diagnosis, and tissue regeneration. [ABSTRACT FROM AUTHOR]

Peptide-based biomimetic underwater adhesives are emerging candidates for understanding the adhesion mechanism of natural proteins secreted by sessile organisms. However, there is a grand challenge in the functional recapitulation of the on-site interfacial spreading, adhesion and spontaneous solidification of native proteins in water using peptide adhesives without applied compressing pressure. Here, a solvent-exchange strategy was utilized to exert the underwater injection, on-site spreading, adhesion and sequential solidification of a series of peptide/polyoxometalate coacervates. The coacervates were first prepared in a mixed solution of water and organic solvents by rationally suppressing the non-covalent interactions. After switching to a water environment, the solvent exchange between bulk water and the organic solvent embedded in the matrix of the peptide/polyoxometalate coacervates recovered the hydrophobic effect by increasing the dielectric constant, resulting in a phase transition from soft coacervates to hard solid with enhanced bulk cohesion and thus compelling underwater adhesive performance. The key to this approach is the introduction of suitable organic solvents, which facilitate the control of the intermolecular interactions and the cross-linking density of the peptide/polyoxometalate adhesives in the course of solidification under the water line. The solvent-exchange method displays fascinating universality and compatibility with different peptide segments. [ABSTRACT FROM AUTHOR]

Abstract Living cells are complex, nonequilibrium supramolecular systems capable of independently and/or cooperatively integrating multiple bio‐supramolecules to execute intricate physiological functions that cannot be accomplished by individual biomolecules. These biological design strategies offer valuable insights for the development of synthetic supramolecular systems with spatially controlled hierarchical structures, which, importantly, exhibit cell‐like responses and functions. The next grand challenge in supramolecular chemistry is to control the organization of multiple types of supramolecules in a single system, thus integrating the functions of these supramolecules in an orthogonal and/or cooperative manner. In this perspective, the recent progress in constructing multicomponent supramolecular soft materials through the hybridization of supramolecules, such as self‐assembled nanofibers/gels and coacervates, with other functional molecules, including polymer gels and enzymes is highlighted. Moreover, results show that these materials exhibit bioinspired responses to stimuli, such as bidirectional rheological responses of supramolecular double‐network hydrogels, temporal stimulus pattern‐dependent responses of synthetic coacervates, and 3D hydrogel patterning in response to reaction–diffusion processes are presented. Autonomous active soft materials with cell‐like responses and spatially controlled structures hold promise for diverse applications, including soft robotics with directional motion, point‐of‐care disease diagnosis, and tissue regeneration.

Liquid-liquid phase separation (LLPS) is a captivating phenomenon in which a uniform mixture spontaneously divides into two liquid phases with differing component concentrations. It is prevalent in soft matter, is observed in systems involving polymers, organic molecules, and proteins, and is influenced by environmental factors and component properties. Recent recognition of LLPS within living organisms reveals its role in creating cellular compartments to orchestrate complex biochemical reactions, requiring distinct boundaries and unhindered molecular movement. Nonmembrane compartments, stemming from cytoplasmic LLPS, such as nucleoli, hold promise for synthetic cell engineering and cellular function insights. Under certain conditions, LLPS is linked to diseases such as sickle-cell disease, cancer, and neurodegenerative diseases. This review offers a concise overview of LLPS in soft matter, emphasizing its relevance in soft material engineering. We delve into fundamental mechanisms, focusing on biological systems, and explore the implications of LLPS, spanning organelles, substance exchange, molecular diffusion, and disease associations. LLPS enables soft material engineering, with applications in biomedicine and bioengineering, shaping future possibilities in bioengineering, from foundational cellular constructs to intricate artificial tissue development.

Cancer cell resistance towards drugs leads to limited drug efficacy and therefore, combination therapy of drugs has emerged as a solution. In addition to this, the importance of a carrier system for the co-delivery of drugs to improve the potential of anti-cancer drug efficacy cannot be overlooked. Nowadays, polymer-rich dense phases of liquid droplets, known as coacervates, have emerged as an appealing option to be utilised as drug carriers. Our previous study which reported the complexation between zein and laponite to form coacervates and their future prospect as dual drug carriers has been extended in this work. The present work has validated the usefulness of the synthesized coacervate as a dual-drug carrier for a hydrophilic drug (cisplatin) and a hydrophobic drug (curcumin) towards a breast cancer cell line (MDA-MB-231). The MTT assay and flow cytometry data for MDA-MB-231 cells suggested that the coacervate carrying dual drugs effectively transported anticancer drugs to the cancer cells, thereby arresting their cell cycle in the S phase (by neutral coacervates, X1) and in the G2/M phase (by charged coacervates, X2). Further, it is also revealed that the amount of cisplatin needed to achieve half maximal inhibitory concentration (IC50) was reduced by a maximum of 70% when flavonoid (curcumin) was used in combination with cisplatin due to synergistic effect.

The precipitate and the coacervate are two aggregated states in the polyelectrolyte complexes (PECs). The precipitate‐to‐coacervate transition and glass transition in PECs have been widely reported in the past. In many cases, the two phenomena are studied independently, although both of them are apparently affected by water and small ions. Here, utilizing a PEC system consisting of poly(acrylic acid) (PAA) and a cationic bolaamphiphile (DBON), we explore the states of PECs as a function of salt, temperature, and the molecular weight of PAAs. By a combination of microscopic observation, time‐resolved fluorescence measurements, and differential scanning calorimetry, we identify salt/temperature driven precipitate‐to‐coacervate transitions of the complexes. The thermally induced morphology transformation from the precipitate to coacervate occurs around the glass transition temperature, indicating a strong correlation between the two processes. As the molecular weight of the PAA increases, the thermal transition temperature becomes higher. This finding offers new insights on the mechanistic interactions that dictate the aggregated states of PECs. Based on the photothermal effect of DBON, we also develop a UV light‐induced strategy to mediate the precipitate‐to‐coacervate transition, providing a fantastic platform to create functional PEC materials. [ABSTRACT FROM AUTHOR]

The freezing of biological fluids is intensively studied but remains elusive as it is affected not only by the various components but also by the crowding nature of the biological fluids. Herein, we constructed spherical crowders, fibrous crowders, and coacervates by various components ranging from surfactants to polymers and proteins, to mimic three typical crowders in biological fluids, i.e. globular proteins, fibrous networks, and condensates of biomolecules. It is elucidated that the three crowders exhibit low, moderate, and strong ice growth inhibition activity, respectively, resulting from their different abilities in slowing down water dynamics. Intriguingly, the coacervate consisting of molecules without obvious ice growth inhibition activity strongly inhibits ice growth, which is firstly employed as a highly‐potent cryoprotectant. This work provides new insights into the survival of freezing‐tolerant organisms and opens an avenue for the design of ice‐controlling materials. [ABSTRACT FROM AUTHOR]

[Display omitted] Marine organisms, such as mussels and sandcastle worms, can master rapid and robust adhesion in turbulent seawater, becoming leading archetypes for the design of underwater adhesives. The adhesive proteins secreted by the organisms are rich in catecholic amino acids along with ionic and amphiphilic moieties, which mediate the adaptive adhesion mainly through catechol chemistry and coacervation process. Catechol allows a broad range of molecular interactions both at the adhesive-substrate interface and within the adhesive matrix, while coacervation promotes the delivery and surface spreading of the adhesive proteins. These natural design principles have been translated to synthetic systems toward the development of biomimetic adhesives with water-resist adhesion and cohesion. This review provides an overview of the recent progress in bio-inspired wet adhesives, focusing on two aspects: (1) the elucidation of the versatile molecular interactions (e.g., electrostatic interactions, metal coordination, hydrogen bonding, and cation-π/anion-π interactions) used by natural adhesives, mainly through nanomechanical characterizations; and (2) the rational designs of wet adhesives based on these biomimetic strategies, which involve catechol-functionalized, coacervation-induced, and hydrogen bond-based approaches. The emerging applications (e.g., tissue glues, surgical implants, electrode binders) of the developed biomimetic adhesives in biomedical, energy, and environmental fields are also discussed, with future research directions proposed. [ABSTRACT FROM AUTHOR]

Abstract The precipitate and the coacervate are two aggregated states in the polyelectrolyte complexes (PECs). The precipitate‐to‐coacervate transition and glass transition in PECs have been widely reported in the past. In many cases, the two phenomena are studied independently, although both of them are apparently affected by water and small ions. Here, utilizing a PEC system consisting of poly(acrylic acid) (PAA) and a cationic bolaamphiphile (DBON), we explore the states of PECs as a function of salt, temperature, and the molecular weight of PAAs. By a combination of microscopic observation, time‐resolved fluorescence measurements, and differential scanning calorimetry, we identify salt/temperature driven precipitate‐to‐coacervate transitions of the complexes. The thermally induced morphology transformation from the precipitate to coacervate occurs around the glass transition temperature, indicating a strong correlation between the two processes. As the molecular weight of the PAA increases, the thermal transition temperature becomes higher. This finding offers new insights on the mechanistic interactions that dictate the aggregated states of PECs. Based on the photothermal effect of DBON, we also develop a UV light‐induced strategy to mediate the precipitate‐to‐coacervate transition, providing a fantastic platform to create functional PEC materials.

Preparation of nitrogen-doped porous activated carbon materials gained much importance in recent years due to their enhanced CO2 adsorption properties and CO2/N2 selectivity as against undoped counterparts. In this study, N-doped activated carbon macrospheres were prepared by carbonization of casein-coated chitosan macrospheres obtained by coacervation method, where chitosan serves as a nitrogen containing carbon (C/N) precursor and casein serves as an additional polymeric nitrogen source. Uncoated chitosan macrospheres were also prepared in NaOH solution for comparative studies. SEM–EDS, CHN analysis, BET surface area analysis, Raman, FTIR, XRD and XPS were performed on both samples to compare the textural characteristics of the activated carbons prepared. Thermal analysis using TGA and DTG revealed that coacervated sample possessed improved thermal stability. The CO2 adsorption studies showed an enhanced adsorption capacity for the activated carbon prepared from chitosan/casein macrospheres (123.57 mg/g) than for the activated carbon from chitosan/NaOH macrospheres (97.98 mg/g) at 25 °C and 1 bar. The activated carbon prepared from chitosan/casein macrospheres exhibited an excellent CO2/N2 selectivity. Furthermore, a steady CO2 uptake studied up to 5 cycles indicates the material is thermally stable and reusable without deterioration in CO2 adsorption capacity. [ABSTRACT FROM AUTHOR]

The counterion effect of nano-ion is recognized as the key to tune the hierarchical structure of its coacervate with polyelectrolyte, and the mechanism is confirmed to be the association of the counterions of nano-ions with the carbonyl groups of the polyelectrolyte, which strengthens the attraction between nano-ions and polyelectrolytes. [Display omitted] Nano-ions can complex with polyelectrolytes for coacervates with hierarchical structures; however, the rational design of functional coacervations is still rare due to the poor understanding of their structure–property relationship from their complex interaction. Herein, 1 nm anionic metal oxide clusters, PW 12 O 40 3-, with well-defined, mono-disperse structures are applied to complex with cationic polyelectrolyte and the system shows tunable coacervation via the alternation of counterions (H+ and Na+) of PW 12 O 40 3-. Suggested from Fourier transform infrared spectroscopy (FT-IR) and isothermal titration studies, the interaction between PW 12 O 40 3- and cationic polyelectrolytes can be modulated by the bridging effect of counterions via hydrogen bonding or ion–dipole interaction to carbonyl groups of polyelectrolytes. The condensed structures of the complexed coacervates are explored by small angle X-ray and neutron scattering techniques, respectively. The coacervate with H+ as counterions shows both crystallized and discrete PW 12 O 40 3- clusters, with a loose polymer-cluster network in comparison to the system of Na+ which shows a dense packing structure with aggregated nano-ions filling the meshes of polyelectrolyte networks. The bridging effect of counterions helps understand the super-chaotropic effect observed in nano-ion system and provides avenues for the design of metal oxide cluster-based functional coacervates. [ABSTRACT FROM AUTHOR]

Biomolecules can undergo liquid-liquid phase separation (LLPS), forming dense droplets that are increasingly understood to be important for cellular function. Analogous systems are studied as early-life compartmentalization mechanisms, for applications as protocells, or as drug-delivery vehicles. In many of these situations, interactions between the droplet and enzymatic solutes are important to achieve certain functions. To explore this, we carried out experiments in which a model LLPS system, formed from DNA "nanostar" particles, interacted with a DNA-cleaving restriction enzyme, SmaI, whose activity degraded the droplets, causing them to shrink with time. By controlling adhesion of the DNA droplet to a glass surface, we were able to carry out time-resolved imaging of this "active dissolution" process. We found that the scaling properties of droplet shrinking were sensitive to the proximity to the dissolution ("boiling") temperature of the dense liquid: For systems far from the boiling point, enzymes acted only on the droplet surface, while systems poised near the boiling point permitted enzyme penetration. This was corroborated by the observation of enzyme-induced vacuole-formation ("bubbling") events, which can only occur through enzyme internalization, and which occurred only in systems poised near the boiling point. Overall, our results demonstrate a mechanism through which the phase stability of a liquid affects its enzymatic degradation through modulation of enzyme transport properties.

Peptide-based biomimetic underwater adhesives are emerging candidates for understanding the adhesion mechanism of natural proteins secreted by sessile organisms. However, there is a grand challenge in the functional recapitulation of the on-site interfacial spreading, adhesion and spontaneous solidification of native proteins in water using peptide adhesives without applied compressing pressure. Here, a solvent-exchange strategy was utilized to exert the underwater injection, on-site spreading, adhesion and sequential solidification of a series of peptide/polyoxometalate coacervates. The coacervates were first prepared in a mixed solution of water and organic solvents by rationally suppressing the non-covalent interactions. After switching to a water environment, the solvent exchange between bulk water and the organic solvent embedded in the matrix of the peptide/polyoxometalate coacervates recovered the hydrophobic effect by increasing the dielectric constant, resulting in a phase transition from soft coacervates to hard solid with enhanced bulk cohesion and thus compelling underwater adhesive performance. The key to this approach is the introduction of suitable organic solvents, which facilitate the control of the intermolecular interactions and the cross-linking density of the peptide/polyoxometalate adhesives in the course of solidification under the water line. The solvent-exchange method displays fascinating universality and compatibility with different peptide segments.

Abstract Background Pancreatic cancer, one of the cancers with the highest mortality rate, has very limited clinical treatment. Cancer cells express abnormal glycans on the surface, and some lectins with a high affinity for the glycans induce apoptosis in cancer. In this study, the efficacy of Aleuria Aurantia lectin (AAL) for the treatment of pancreatic cancer was evaluated and the efficacy improvement through AAL delivery with mPEGylated coacervate (mPEG-Coa) was investigated. Methods AAL was treated with pancreatic cancer cells, PANC-1, and the expression level of caspase-3 and subsequent apoptosis was analyzed. In particular, the anticancer efficacy of AAL was compared with that of concanavalin A, one of the representative anticancer lectins. Then, methoxypolyethylene glycol-poly(ethylene arginylaspartate diglyceride), a polycation, was synthesized, and an mPEG-Coa complex was prepared with polyanion heparin. The AAL was incorporated into the mPEG-Coa and the release kinetics of the AAL from the mPEG-Coa and the cargo protection capacity of the mPEG-Coa were evaluated. Finally, improved anticancer ability through Coa-mediated AAL delivery was assessed. Results These results indicated that AAL is a potential effective pancreatic cancer treatment. Moreover, mPEG-Coa rapidly released AAL at pH 6.5, an acidic condition in the cancer microenvironment. The initial rapid release of AAL effectively suppressed pancreatic cancer cells, and the continuous supply of AAL through the Coa transporter effectively inhibited proliferation recurrence of cancer cells. Conclusion AAL is a potential novel drug for the treatment of pancreatic cancer therapeutic agent. In addition, a continuous supply of drugs above the therapeutic threshold using mPEG-Coa could improve therapeutic efficacy.

To date, it has been shown that the phenomenon of liquid–liquid phase separation (LLPS) underlies many seemingly completely different cellular processes. This provided a new idea of the spatiotemporal organization of the cell. The new paradigm makes it possible to provide answers to many long-standing, but still unresolved questions facing the researcher. In particular, spatiotemporal regulation of the assembly/disassembly of the cytoskeleton, including the formation of actin filaments, becomes clearer. To date, it has been shown that coacervates of actin-binding proteins that arise during the phase separation of the liquid–liquid type can integrate G-actin and thereby increase its concentration to initiate polymerization. It has also been shown that the activity intensification of actin-binding proteins that control actin polymerization, such as N-WASP and Arp2/3, can be caused by their integration into liquid droplet coacervates formed by signaling proteins on the inner side of the cell membrane. [ABSTRACT FROM AUTHOR]

Diabetic wounds are challenging to heal due to complex pathogenic abnormalities. Routine treatment with acid fibroblast growth factor (aFGF) is widely used for diabetic wounds but hardly offers a satisfying outcome due to its instability. Despite the emergence of various nanoparticle-based protein delivery approaches, it remains challenging to engineer a versatile delivery system capable of enhancing protein stability without the need for complex preparation. Herein, a polyphenol-driven facile assembly of nanosized coacervates (AE-NPs) composed of aFGF and Epigallocatechin-3-gallate (EGCG) was constructed and applied in the healing of diabetic wounds. First, the binding patterns of EGCG and aFGF were predicted by molecular docking analysis. Then, the characterizations demonstrated that AE-NPs displayed higher stability in hostile conditions than free aFGF by enhancing the binding activity of aFGF to cell surface receptors. Meanwhile, the AE-NPs also had a powerful ability to scavenge reactive oxygen species (ROS) and promote angiogenesis, which significantly accelerated full-thickness excisional wound healing in diabetic mice. Besides, the AE-NPs suppressed the early scar formation by improving collagen remodeling and the mechanism was associated with the TGF-β/Smad signaling pathway. Conclusively, AE-NPs might be a potential and facile strategy for stabilizing protein drugs and achieving the scar-free healing of diabetic wounds. Diabetic chronic wound is among the serious complications of diabetes that eventually cause the amputation of limbs. Herein, a polyphenol-driven facile assembly of nanosized coacervates (AE-NPs) composed of aFGF and EGCG was constructed. The EGCG not only acted as a carrier but also possessed a therapeutic effect of ROS scavenging. The AE-NPs enhanced the binding activity of aFGF to cell surface receptors on the cell surface, which improved the stability of aFGF in hostile conditions. Moreover, AE-NPs significantly accelerated wound healing and improved collagen remodeling by regulating the TGF-β/Smad signaling pathway. Our results bring new insights into the field of polyphenol-containing nanoparticles, showing their potential as drug delivery systems of macromolecules to treat diabetic wounds. [Display omitted] [ABSTRACT FROM AUTHOR]

[Display omitted] Colloidosomes made of stimuli-responsive microgels offer the opportunity to design polymeric capsules with a hierarchical and tunable pore distribution. Coacervates stabilized by a microgel monolayer represent a unique strategy to build colloidosomes from all-aqueous emulsion drops, while exploiting the sequestration and dissolution properties of the coacervates. Methacrylated poly(N -isopropylacrylamide) (pNIPAM) microgels are used to stabilize coacervates made of an ampholyte polymer at a pH close to its isoelectric point. They are further cross-linked under UV-irradiation. The resulting assemblies are studied by means of confocal microscopy. Their permeability towards dextrans and nanoparticles is studied before and after dissolution of the coacervate. PNIPAM microgels are found to stabilize the coacervates by adsorbing at their surface. Inter cross-linking the microgels results in the formation of an elastic colloidosome that persists after the coacervate dissolution and withstands surface deformations up to about 200%. The coacervate is exploited as a sequestrating core to entrap a water-soluble payload, which can be further released upon coacervate dissolution, while the membrane exhibits a size-selecting permeability. The membrane properties can also be switched by the volume phase transition of the microgels. Coacervate-embedded colloidosomes open new perspectives in the area of encapsulation/extraction and controlled transport of water-soluble/dispersed species. [ABSTRACT FROM AUTHOR]

Coacervates are droplets formed by liquid‒liquid phase separation. An increasing number of studies have reported that coacervates play an important role in living cells, such as in the generation of membraneless organelles, and peptides contribute to condensate droplet formation. Peptides with versatile functional groups and special secondary structures, including α-helices, β-sheets and intrinsically disordered regions, provide novel insights into coacervation, such as biomimetic protocells, neurodegenerative diseases, modulations of signal transmission, and drug delivery systems. In this review, we introduce different types of peptide-based coacervates and the principles of their interactions. Additionally, we summarize the thermodynamic and kinetic mechanisms of peptide-based coacervates and the associated factors, including salt, pH, and temperature, affecting the phase separation process. We illustrate recent studies on modulating the functions of peptide-based coacervates applied in biological diseases. Finally, we propose their promising broad applications and describe the challenges of peptide-based coacervates in the future.

The origin of life on Earth remains one of the biggest open questions in science. Despite recent advances in molecular mechanism of cell biology, a large blind spot still exists between non-living matter and the emergence of life which cannot be filled by biology alone. The quest to comprehend the cell origin inspires the construction of synthetic analogs (protocells) to mimic their life-like functionality and structural complexity. Among all kinds, coacervates formed by liquid-liquid phase separation featured by their dynamic structure, molecularly crowded interior and molecular sequestration capability, have been regarded as a protocell model for exploring the origin of life. Their biological counterparts in natural cells are also found to facilitate subcellular organization and spatiotemporal regulation of biological molecules. In this tutorial review, we summarize the recent progress on engineering coacervate protocells to potentially reproduce the function and structure of primitive life by multiphase organization, membranization and structural hybridization. Routes to high-ordered protocellular system comprising spatially arranged coacervates, as well as to the construction of tissue-like structures are also described. Finally, we deduce some perspectives of coacervate engineering in the direction of the emergence of life, from molecular scale to the emergence of integrated multicellular system.

Inorganic polyphosphates (polyP) are of increasing medical interest due to their unprecedented ability to exhibit both morphogenetic and ATP-delivering properties. However, these polymers are only physiologically active in the coacervate state, but not as amorphous nanoparticles (NP), the storage form of the polymer. Little is known about the mechanism of formation and interconversion of these two distinct polyP phases in the presence of metal ions. Based on in silico simulation studies, showing a differential clustering of polyP and calcium ions, the pH-dependent NP and coacervate formation of polyP was examined experimentally. Turbidimetric studies showed that Ca-polyP coacervate formation at pH 7 is a slow process compared to NP formation at pH 10. In FTIR spectra, the asymmetric stretching vibration signal of the internal (PO2)− units, which is present in the Ca-polyP coacervate formed at pH 7, disappears in the NP formed at pH 10 using the conventional method (dropping of a CaCl2 solution into a Na-polyP solution). Surprisingly, when reversing the procedure, adding Na-polyP to CaCl2, a coacervate is obtained at both pH 7 and pH 10, as confirmed by SEM and FTIR analyses. The (PO2)− signal also disappears when Ca-polyP-NP are exposed to peptides, leading to the transformation of the NP into the coacervate phase. From these results, a mechanistic model of pH-dependent coacervate and NP formation is proposed that considers not only electrostatic ion-ion but also ion-dipole interactions. Functional studies revealed a delayed polyP release kinetics for Ca-polyP-NP embedded in a hydrogel due to NP/coacervate conversion. Human A549 epithelial cells grown on the coacervate show increased proliferation and ATP production compared to cells cultured on particulate polyP. Ca-polyP NP taken up by endocytosis undergo intracellular coacervate transformation. Understanding the differential expression of the two polyP phases is of functional importance for the potential therapeutic application of this physiological, regeneratively active polymer.

Achieving robust underwater adhesion by bioadhesives remains a challenge due to interfacial water. Herein a coacervate‐to‐hydrogel strategy to enhance interfacial water repulsion and bulk adhesion of bioadhesives is reported. The polyethyleneimine/thioctic acid (PEI/TA) coacervate is deposited onto underwater substrates, which can effectively repel interfacial water and completely spread into substrate surface irregularities due to its liquid and water‐immiscible nature. The physical interactions between coacervate and substrate can further enhance interfacial adhesion. Furthermore, driven by the spontaneous hydrophobic aggregation of TA molecules and strong electrostatic interaction between PEI and TA, the coacervate can turn into a hydrogel in situ within minutes without additional stimuli to develop enhanced matrix cohesion and robust bulk adhesion on diverse underwater substrates. Molecular dynamics simulations further reveal atomistic details of the formation and wet adhesion of the PEI/TA coacervate via multimode physical interactions. Lastly, it is demonstrated that the PEI/TA coacervate‐derived hydrogel can effectively repel blood and therefore efficiently deliver the carried growth factors at wound sites, thereby enhancing wound healing in an animal model. The advantages of the PEI/TA coacervate‐derived hydrogel including body fluid‐immiscibility, strong underwater adhesion, adaptability to fit irregular target sites, and excellent biocompatibility make it a promising bioadhesive for diverse biomedical applications. [ABSTRACT FROM AUTHOR]

Abstract Achieving robust underwater adhesion by bioadhesives remains a challenge due to interfacial water. Herein a coacervate‐to‐hydrogel strategy to enhance interfacial water repulsion and bulk adhesion of bioadhesives is reported. The polyethyleneimine/thioctic acid (PEI/TA) coacervate is deposited onto underwater substrates, which can effectively repel interfacial water and completely spread into substrate surface irregularities due to its liquid and water‐immiscible nature. The physical interactions between coacervate and substrate can further enhance interfacial adhesion. Furthermore, driven by the spontaneous hydrophobic aggregation of TA molecules and strong electrostatic interaction between PEI and TA, the coacervate can turn into a hydrogel in situ within minutes without additional stimuli to develop enhanced matrix cohesion and robust bulk adhesion on diverse underwater substrates. Molecular dynamics simulations further reveal atomistic details of the formation and wet adhesion of the PEI/TA coacervate via multimode physical interactions. Lastly, it is demonstrated that the PEI/TA coacervate‐derived hydrogel can effectively repel blood and therefore efficiently deliver the carried growth factors at wound sites, thereby enhancing wound healing in an animal model. The advantages of the PEI/TA coacervate‐derived hydrogel including body fluid‐immiscibility, strong underwater adhesion, adaptability to fit irregular target sites, and excellent biocompatibility make it a promising bioadhesive for diverse biomedical applications.

Colon cancer (CC) belongs to the three major malignancies with a high recurrence rate. Therefore, a novel drug delivery system that can prevent CC recurrence while minimizing side effects is needed. Tumor-necrosis-factor-related apoptosis-inducing ligand (TRAIL) has recently been spotlighted as a protein drug that can induce apoptosis of cancer cells specifically. However, its short in vivo half-life is still a challenge to overcome. Hence, in this study, a gel-like mPEGylated coacervate (mPEG-Coa) delivery platform was developed through electrostatic interaction of mPEG-poly(ethylene arginylaspartate diglyceride) (mPEG-PEAD) and heparin for effective protection of cargo TRAIL, subsequently preserving its bioactivity. mPEG-Coa could protect cargo TRAIL against protease. Sustained release was observed for a long-term (14 days). In addition, recurrence of HCT-116 cells was suppressed when cells were treated with TRAIL-loaded mPEG-Coa for 7 days through long-term continuous supply of active TRAIL, whereas re-proliferation occurred in the bolus TRAIL-treated group. Taken together, these results suggest that our gel-like mPEG-Coa could be utilized as a functional delivery platform to suppress CC recurrence by exogenously supplying TRAIL for a long time with a single administration. [ABSTRACT FROM AUTHOR]

[Display omitted] The liquid-liquid phase separation (LLPS) of amphiphilic thermoresponsive copolymers can lead to the formation of micron-sized domains, known as simple coacervates. Due to their potential to confine active principles, these copolymer-rich droplets have gained interest as encapsulating agents. Understanding and controlling the conditions inducing this LLPS is therefore essential for applicative purposes and requires thorough fundamental studies on self-coacervation. In this work, we investigate the LLPS of a comb-like graft copolymer (PEG-g-PVAc) consisting of a poly(ethylene glycol) backbone (6 kDa) with ∼2–3 grafted poly(vinyl acetate) chains, and a PEG/PVAc weight ratio of 40/60. Specifically, we report the effect of various water-soluble additives on its phase separation behavior. Kosmotropes and non-ionic surfactants were found to decrease the phase separation temperature of the copolymer, while chaotropes and, above all, ionic surfactants increased it. We then focus on the phase behavior of PEG-g-PVAc in the presence of sodium citrate and a C 14-15 E 7 non-ionic surfactant (N45-7), defining the compositional range for the generation of LLPS microdomains at room temperature and monitoring their formation with fluorescence confocal microscopy. Finally, we determine the composition of the microdomains through confocal Raman microscopy, demonstrating the presence of PEG-g-PVAc, N45-7, and water. These results expand our knowledge on polymeric self-coacervation, clarifying the optimal conditions and composition needed to obtain LLPS microdomains with encapsulation potential at room temperature in surfactant-rich formulations. [ABSTRACT FROM AUTHOR]

Heart disease is still the leading killer all around the world, and its incidence is expected to increase over the next decade. Previous reports have already shown the role of fibroblast growth factor10 (FGF10) in alleviating heart diseases. However, FGF10 has not been used to treat heart diseases because the free protein has short half-life and low bioactivity. Here, an injectable coacervate was designed to protect growth factor from degradation during delivery and the effects of the FGF10 coacervate were studied using a mice acute myocardial infarction (MI) model. As shown in our echocardiographic results, a single injection of FGF10 coacervate effectively inhibited preserved cardiac contractibility and ventricular dilation when compared with free FGF10 and the saline treatment 6 weeks after MI. It is revealed in histological results that the MI induced myocardial inflammation and fibrosis was reduced after FGF10 coacervate treatment. Furthermore, FGF10 coacervate treatment could improve arterioles and capillaries stabilization through increasing the proliferation of endothelial and mural cells. However, with the same dosage, no statistically significant difference was shown between free FGF10, heparin+FGF10 and saline treatment, especially in long term. On another hand, FGF10 coacervate also increased the expression of cardiac-associated the mRNA (cTnT, Cx43 and α-SMA), angiogenic factors (Ang-1 and VEGFA) and decreased the level of inflammatory factor (tumor necrosis factor-α). The downstream signaling of the FGF10 was also investigated, with the western blot results showing that FGF10 coacervate activated the p-FGFR, PI3K/Akt and ERK1/2 pathways to a more proper level than free FGF10 or heparin+FGF10. In general, it is revealed in this research that one-time injection of FGF10 coacervate sufficiently attenuated MI induced injury when compared with an equal dose of free FGF10 or heparin+FGF10 injection.

Chronic stress promotes TNBC metastasis by nerve-tumor-immune interaction loop. Propranolol-loaded coacervate (Pro@Coa) exhibits favorable intratumoral enrichment and sustained release of propranolol. Pro@Coa can not only inhibit TNBC metastasis by disrupting the nerve-tumor-immune loop but also suppress distant tumor growth by inducing systemic immunity. [Display omitted] • Chronic stress promotes TNBC metastasis by nerve-tumor-immune interaction loop. • Coacervate shows favorable sustained drug release ability, biosafety, and easy synthetic transformation. • Pro@Coa can block the nerve-tumor-immune loop to inhibit TNBC metastasis. • Pro@Coa can induce systemic immunity to suppress TNBC distant tumor growth. Chronic stress, a common comorbidity of breast cancer, is shown to promote tumor progression by affecting tumor microenvironment. Metastasis is the leading cause of death in triple-negative breast cancer (TNBC), and clarifying the specific role of chronic stress on TNBC metastasis will facilitate the development of new targets and improve its prognosis. In this study, a reciprocal nerve-tumor-immune loop is firstly depicted to promote TNBC metastasis under chronic stress and can be interrupted by propranolol (Pro), which shows rapid clinical translation potential due to "new uses for old drugs". However, low bioavailability and insufficient efficacy of Pro when applied systemically may hinder its clinical translation in cancer patients. Based on this, an injectable and pH-responsive Pro-loaded coacervate (Pro@Coa) is further developed, which can accumulate and sustainably release Pro within the tumor. For the first time, the study demonstrates that Pro@Coa not only inhibits TNBC metastasis by interrupting the reciprocal loop but also suppresses distant tumor growth by inducing systemic immunity. Compared to traditional free Pro administration, Pro@Coa improves treatment efficiency and has no side effects on normal tissues. Overall, this work delineates a nerve-tumor-immune loop that promotes TNBC metastasis under chronic stress and provides a reference for applying Pro@Coa for safer and more effective treatment of TNBC metastasis, which is more promising for clinical translation. [ABSTRACT FROM AUTHOR]

The delivery of functional proteins, including antibodies, into cells opens up many opportunities to regulate cellular events, with significant implications for studies in chemical biology and therapeutics. The inside of cells is isolated from the outside by the cell membrane. The hydrophilic nature of proteins prevents direct permeation of proteins through the cell membrane by passive diffusion. Therefore, delivery routes using endocytic uptake followed by endosomal escape have been explored. Alternatively, delivery concepts using transient permeabilization of cell membranes or effective promotion of endocytic uptake and endosomal escape using modified membrane-lytic peptides have been reported in recent years. Non-canonical protein delivery concepts, such as the use of liquid droplets or coacervates, have also been proposed. This review highlights some of the topics in peptide-mediated intracellular protein delivery. [ABSTRACT FROM AUTHOR]

The transition from soluble to colloidal polyelectrolyte complex normally occurs at a critical non‐stoichiometric charge ratio. Here, it is demonstrated that the conventional batch mixing produces heterogeneous binding and complexation, which can easily mask this soluble‐colloidal complex transition (sol‐col transition) even for weakly binding polyelectrolytes like polyacrylic acid (PAA) and poly(diallyldimethylammonium chloride) (PDADMAC). When mixed efficiently using multi‐inlet vortex mixer (MIVM), the sol‐col transition occurs beyond a critical charge ratio (n−/n+) and the large colloidal complexes are formed through the aggregation of small primary complexes (as revealed by atomic force microscopy). Moreover, the sol‐col transition occurs at a constant charge ratio below the overlapping concentration (c*) of the long host polyelectrolyte, but at lower charge ratios above c* due to chain entanglement. When adding NaCl to the solution, the sol‐col transition charge ratio first decreases, then remained stable for a period, and finally increased and vanished at high ionic strength. When replacing NaCl with chaotropic salts, the sol‐col transition occurs at lower charge ratios, while kosmotropes has little impact. The solvent quality and polymer hydrophobicity effects are also discussed. With the assistance of rapid mixing, this study provides a more reliable way of studying the sol‐col transition of polyelectrolyte complexes. [ABSTRACT FROM AUTHOR]

Two coacervate phases with different microstructures were constructed with cationic quaternary ammonium gemini surfactant hexamethylene-1,6-bis(dodecyldimethylammonium bromide) (12-6-12), sodium benzoate (NaBz) and sodium carboxymethylcellulose (NaCMC), and the anionic dye methyl orange (MO) was extracted from aqueous solution. The experiments results showed that the coacervate phases of 12-6-12/ NaBz and 12-6-12/NaBz/NaCMC were respectively worm-like micelle entanglement and three-dimensional network structure, and they had great efficiency in the extraction of MO from water. Moreover, the two coacervate phases could selectively extract anionic dye MO in the presence of cationic dye methylene blue. The possible extraction mechanism could be that after adding MO into the coacervate phase, some MO molecules were embedded into the 12-6-12 micellar core through the benzene ring structure, and some MO molecules were adsorbed on the 12-6-12 micellar surface, which participated in the formation of the coacervate phase with network structure. [ABSTRACT FROM AUTHOR]

Two biocatalytically produced inorganic biomaterials show great potential for use in regenerative medicine but also other medical applications: bio-silica and bio-polyphosphate (bio-polyP or polyP). Biosilica is synthesized by a group of enzymes called silicateins, which mediate the formation of amorphous hydrated silica from monomeric precursors. The polymeric silicic acid formed by these enzymes, which have been cloned from various siliceous sponge species, then undergoes a maturation process to form a solid biosilica material. The second biomaterial, polyP, has the extraordinary property that it not only has morphogenetic activity similar to biosilica, i.e., can induce cell differentiation through specific gene expression, but also provides metabolic energy through enzymatic cleavage of its high-energy phosphoanhydride bonds. This reaction is catalyzed by alkaline phosphatase, a ubiquitous enzyme that, in combination with adenylate kinase, forms adenosine triphosphate (ATP) from polyP. This article attempts to highlight the biomedical importance of the inorganic polymeric materials biosilica and polyP as well as the enzymes silicatein and alkaline phosphatase, which are involved in their metabolism or mediate their biological activity. [ABSTRACT FROM AUTHOR]

To date, it has been shown that the phenomenon of liquid–liquid phase separation (LLPS) underlies many seemingly completely different cellular processes. This provided a new idea of the spatiotemporal organization of the cell. The new paradigm makes it possible to provide answers to many long-standing, but still unresolved questions facing the researcher. In particular, spatiotemporal regulation of the assembly/disassembly of the cytoskeleton, including the formation of actin filaments, becomes clearer. To date, it has been shown that coacervates of actin-binding proteins that arise during the phase separation of the liquid–liquid type can integrate G-actin and thereby increase its concentration to initiate polymerization. It has also been shown that the activity intensification of actin-binding proteins that control actin polymerization, such as N-WASP and Arp2/3, can be caused by their integration into liquid droplet coacervates formed by signaling proteins on the inner side of the cell membrane.

Excessive usage of biologically toxic fungicides and their matrix materials poses a serious threat to public health. Leveraging fungicide carriers with inherent pathogen inhibition properties is highly promising for enhancing fungicide efficacy and reducing required dosage. Herein, a series of coacervates have been crafted with lignin and surfactin, both of which are naturally derived and demonstrate substantial antifungal properties. This hierarchically assembled carrier not only effectively loads fungicides with a maximum encapsulation efficiency of 95% but also stably deposits on hydrophobic leaves for high-speed impacting droplets. Intriguingly, these coacervates exhibit broad spectrum fungicidal activity against eight ubiquitous phytopathogens and even act as a standalone biofungicide to replace fungicides. This performance can significantly reduce the fungicide usage and be further strengthened by an encapsulated fungicide. The inhibition rate reaches 87.0% when 0.30 mM pyraclostrobin (Pyr) is encapsulated within this coacervate, comparable to the effectiveness of 0.80 mM Pyr alone. Additionally, the preventive effects against tomato gray mold reached 53%, significantly surpassing those of commercial adjuvants. Thus, it demonstrates that utilizing biosurfactants and biomass with intrinsic antifungal activity to fabricate fully biobased coacervates can synergistically combine the functions of a fungicide carrier and antifungal agent against phytopathogens and guarantee environmental friendliness. This pioneering approach provides deeper insights into synergistically enhancing the effectiveness of agrochemicals from multiple aspects, including fungicide encapsulation, cooperative antifungal action, and droplet deposition.

Objective . Macrophages and astrocytes play a crucial role in the aftermath of a traumatic spinal cord injury (SCI). Infiltrating macrophages adopt a pro-inflammatory phenotype while resident astrocytes adopt a neurotoxic phenotype at the injury site, both of which contribute to neuronal death and inhibit axonal regeneration. The cytokine interleukin-4 (IL-4) has shown significant promise in preclinical models of SCI by alleviating the macrophage-mediated inflammation and promoting functional recovery. However, its effect on neurotoxic reactive astrocytes remains to be elucidated, which we explored in this study. We also studied the beneficial effects of a sustained release of IL-4 from an injectable biomaterial compared to bolus administration of IL-4. Approach . We fabricated a heparin-based coacervate capable of anchoring and releasing bioactive IL-4 and tested its efficacy in vitro and in vivo. Main results . We show that IL-4 coacervate is biocompatible and drives a robust anti-inflammatory macrophage phenotype in culture. We also show that IL-4 and IL-4 coacervate can alleviate the reactive neurotoxic phenotype of astrocytes in culture. Finally, using a murine model of contusion SCI, we show that IL-4 and IL-4 coacervate, injected intraspinally 2 d post-injury, can reduce macrophage-mediated inflammation, and alleviate neurotoxic astrocyte phenotype, acutely and chronically, while also promoting neuroprotection with significant improvements in hindlimb locomotor recovery. We observed that IL-4 coacervate can promote a more robust regenerative macrophage phenotype in vitro , as well as match its efficacy in vivo, compared to bolus IL-4. Significance . Our work shows the promise of coacervate as a great choice for local and prolonged delivery of cytokines like IL-4. We support this by showing that the coacervate can release bioactive IL-4, which acts on macrophages and astrocytes to promote a pro-regenerative environment following a SCI leading to robust neuroprotective and functional outcomes., (© 2024 IOP Publishing Ltd.)

Nanoparticles of a particular, evolutionarily old inorganic polymer found across the biological kingdoms have attracted increasing interest in recent years not only because of their crucial role in metabolism but also their potential medical applicability: it is inorganic polyphosphate (polyP). This ubiquitous linear polymer is composed of 10-1000 phosphate residues linked by high-energy anhydride bonds. PolyP causes induction of gene activity, provides phosphate for bone mineralization, and serves as an energy supplier through enzymatic cleavage of its acid anhydride bonds and subsequent ATP formation. The biomedical breakthrough of polyP came with the development of a successful fabrication process, in depot form, as Ca- or Mg-polyP nanoparticles, or as the directly effective polymer, as soluble Na-polyP, for regenerative repair and healing processes, especially in tissue areas with insufficient blood supply. Physiologically, the platelets are the main vehicles for polyP nanoparticles in the circulating blood. To be biomedically active, these particles undergo coacervation. This review provides an overview of the properties of polyP and polyP nanoparticles for applications in the regeneration and repair of bone, cartilage, and skin. In addition to studies on animal models, the first successful proof-of-concept studies on humans for the healing of chronic wounds are outlined., (© 2024 The Authors. Small published by Wiley‐VCH GmbH.)

Transcatheter arterial chemoembolization (TACE) has proven effective in blocking tumor-supplied arteries and delivering localized chemotherapeutic treatment to combat tumors. However, traditional embolic TACE agents exhibit certain limitations, including insufficient chemotherapeutic drug-loading and sustained-release capabilities, non-biodegradability, susceptibility to aggregation, and unstable mechanical properties. This study introduces a novel approach to address these shortcomings by utilizing a complex coacervate as a liquid embolic agent for tumor chemoembolization. By mixing oppositely charged quaternized chitosan (QCS) and gum arabic (GA), a QCS/GA polymer complex coacervate with shear-thinning property is obtained. Furthermore, the incorporation of the contrast agent Iohexol (I) and the chemotherapeutic doxorubicin (DOX) into the coacervate leads to the development of an X-ray-opaque QCS/GA/I/DOX coacervate embolic agent capable of carrying drugs. This innovative formulation effectively embolizes the renal arteries without recanalization. More importantly, the QCS/GA/I/DOX coacervate can successfully embolize the supplying arteries of the VX2 tumors in rabbit ear and liver. Coacervates can locally release DOX to enhance its therapeutic effects, resulting in excellent antitumor efficacy. This coacervate embolic agent exhibits substantial potential for tumor chemoembolization due to its shear-thinning performance, excellent drug-loading and sustained-release capabilities, good biocompatibility, thrombogenicity, biodegradability, safe and effective embolic performance, and user-friendly application., (© 2024 Wiley‐VCH GmbH.)