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Advanced Science (Weinheim,... Aug 2023Gene therapy that employs therapeutic nucleic acids to modulate gene expression has shown great promise for diseases therapy, and its clinical application relies on the...
Gene therapy that employs therapeutic nucleic acids to modulate gene expression has shown great promise for diseases therapy, and its clinical application relies on the development of effective gene vector. Herein a novel gene delivery strategy by just using natural polyphenol (-)-epigallocatechin-3-O-gallate (EGCG) as raw material is reported. EGCG first intercalates into nucleic acids to yield a complex, which then oxidizes and self-polymerizes to form tea polyphenols nanoparticles (TPNs) for effective nucleic acids encapsulation. This is a general method to load any types of nucleic acids with single or double strands and short or long sequences. Such TPNs-based vector achieves comparable gene loading capacity to commonly used cationic materials, but showing lower cytotoxicity. TPNs can effectively penetrate inside cells, escape from endo/lysosomes, and release nucleic acids in response to intracellular glutathione to exert biological functions. To demonstrate the in vivo application, an anti-caspase-3 small interfering ribonucleic acid is loaded into TPNs to treat concanavalin A-induced acute hepatitis, and excellent therapeutic efficacy is obtained in combination with the intrinsic activities of TPNs vector. This work provides a simple, versatile, and cost-effective gene delivery strategy. Given the biocompatibility and intrinsic biofunctions, this TPNs-based gene vector holds great potential to treat various diseases.
Topics: Polyphenols; Tea; Polymerization; Genetic Therapy; Nucleic Acids
PubMed: 37349886
DOI: 10.1002/advs.202302620 -
Acta Biomaterialia Nov 2023Biodegradable polymer-based therapeutics have recently become essential drug delivery biomaterials for various bioactive compounds. Biodegradable and biocompatible...
Biodegradable polymer-based therapeutics have recently become essential drug delivery biomaterials for various bioactive compounds. Biodegradable and biocompatible polymer-based biomaterials fulfill the requirements of these therapeutics because they enable to obtain polymer biomaterials with optimized blood circulation, pharmacokinetics, biodegradability, and renal excretion. Herein, we describe an adaptable polymerization platform employed for the synthesis of long-circulating, stimulus-sensitive and biodegradable biomaterials, therapeutics, or theranostics. Four chain transfer agents (CTA) were designed and successfully synthesized for the reversible addition-fragmentation chain transfer polymerization, allowing the straightforward synthesis of hydrolytically biodegradable structures of block copolymers-based biomaterials. The controlled polymerization using the CTAs enables controlling the half-life of the hydrolytic degradation of polymer precursors in a wide range from 5 h to 21 days. Moreover, the antitumor drug pirarubicin (THP) was successfully conjugated to the polymer biomaterials via a pH-sensitive hydrazone bond for in vitro and in vivo experiments. Polymer conjugates demonstrated superior antitumor efficacy compared to basic linear polymer-based conjugates. Notably, the biodegradable systems, even though those with degradation in the order of hours were selected, increased the half-life of THP in the bloodstream almost two-fold. Indeed, the presented platform design enables the main chain-end specific attachment of targeting ligands or diagnostic molecules. The adaptable polymerization platform design allows tuning of the biodegradability rate, stimuli-sensitive drug bonding, and optimized pharmacokinetics to increase the therapy outcome and system targeting, thus allowing the preparation of targeted or theranostic polymer conjugates. STATEMENT OF SIGNIFICANCE: Biodegradable and biocompatible polymer-based biomaterials are recognized as potential future bioactive nanomedicines. To advance the development of such biomaterials, we developed polymerization platforms utilizing tailored chain transfer agents allowing the straightforward synthesis of hydrolytically degradable polymer biomaterials with tuned biodegradability from hours to several days. The platform allows for the synthesis of long-circulating, stimulus-sensitive and biodegradable biomaterial serving as drug carriers or theranostics. The therapeutic potential was validated by preparation of polymer biomaterials containing pirarubicin, anticancer drug, bound via pH sensitive bond and by showing prolonged blood circulation and increased antitumor activity while keeping the drug side effects low. This work paves the way for future development of biodegradable polymer biomaterials with advanced properties in drug delivery.
Topics: Polymerization; Doxorubicin; Antineoplastic Agents; Drug Carriers; Polymers; Biocompatible Materials
PubMed: 37696413
DOI: 10.1016/j.actbio.2023.09.004 -
Nature Communications Dec 2023Migration of T cells is essential for their ability to mount immune responses. Chemokine-induced T cell migration requires WNK1, a kinase that regulates ion influx into...
Migration of T cells is essential for their ability to mount immune responses. Chemokine-induced T cell migration requires WNK1, a kinase that regulates ion influx into the cell. However, it is not known why ion entry is necessary for T cell movement. Here we show that signaling from the chemokine receptor CCR7 leads to activation of WNK1 and its downstream pathway at the leading edge of migrating CD4 T cells, resulting in ion influx and water entry by osmosis. We propose that WNK1-induced water entry is required to swell the membrane at the leading edge, generating space into which actin filaments can polymerize, thereby facilitating forward movement of the cell. Given the broad expression of WNK1 pathway proteins, our study suggests that ion and water influx are likely to be essential for migration in many cell types, including leukocytes and metastatic tumor cells.
Topics: Actins; Polymerization; Cell Movement; Actin Cytoskeleton; Signal Transduction
PubMed: 38057317
DOI: 10.1038/s41467-023-43423-8 -
The Science of the Total Environment Oct 2023Plastic pollution is a critical problem that has the potential for long-lasting impact. While all plastics eventually break down to at least some degree, they can remain... (Review)
Review
Plastic pollution is a critical problem that has the potential for long-lasting impact. While all plastics eventually break down to at least some degree, they can remain in different transition states, such as microplastics and nanoplastics, for extended periods of time before reaching complete mineralisation to non-hazardous end products. Each of the transition states represents different types of hazards, so it is critical to understand the factors driving the lifetimes of plastics within these states. To do this, we propose a framework for assessing plastic lifetimes in natural environments based on the flow of material through potentially hazardous states: macroplastic and mesoplastic, microplastic, nanoplastic and soluble products. State changes within this framework are underpinned by three key processes: fragmentation, depolymerisation, and bioassimilation, with the pathways for generation of the different plastic states, and the lifetimes within these states, varying widely for individual materials in different environments due to their dependence on polymer material type, form and properties, and environmental factors. The critical factors driving these processes can therefore appear complex, but molecular weight, crystallinity, oxygen and water diffusivity, and inherent polymer chain reactivity (including to enzymes) are key to our understanding. By analysing currently available data that take factors such as these into consideration, we have generated information on the most likely states in which a range of plastics with different environmental degradation behaviour may exist over time in natural environments. Polyethylene (PE), for example, should be expected to fragment and accumulate in the environment as microplastic and nanoplastic. Interestingly, the state-profile for the biodegradable plastic polylactic acid (PLA) is similar, albeit over shorter timeframes. PLA also likely fragments, but then the relatively slow process of abiotic depolymerisation results in accumulation of microplastic and nanoplastic. By contrast, the state-profile for the biodegradable plastic polyhydroxyalkanoate (PHA) would be expected to be very different. The bulk material is less susceptible to embrittlement and fragmentation as a primary path to biodegradation, since the rapid enzyme catalysed depolymerisation of exposed surfaces proceeds in conjunction with bioassimilation.
Topics: Biodegradable Plastics; Plastics; Microplastics; Polyesters; Polymers; Biodegradation, Environmental; Water Pollutants, Chemical
PubMed: 37348710
DOI: 10.1016/j.scitotenv.2023.165025 -
Molecules (Basel, Switzerland) Jun 2023In this work, a novel bio-based high-performance bisbenzoxazine resin was synthesized from daidzein, 2-thiophenemethylamine and paraformaldehyde. The chemical structure...
In this work, a novel bio-based high-performance bisbenzoxazine resin was synthesized from daidzein, 2-thiophenemethylamine and paraformaldehyde. The chemical structure was confirmed using nuclear magnetic resonance spectroscopy (NMR) and Fourier-transform infrared spectroscopy (FT-IR). The polymerization process was systematically studied using differential scanning calorimetry (DSC) and in situ FT-IR spectra. It can be polymerized through multiple polymerization behaviors under the synergistic reaction of thiophene rings with benzopyrone rather than a single polymerization mechanism of traditional benzoxazines, as reported. In addition, thermogravimetric analysis (TGA) and a microscale combustion calorimeter (MCC) were used to study the thermal stability and flame retardancy of the resulting polybenzoxazine. The thermosetting material showed a high carbon residue rate of 62.8% and a low heat release capacity (HRC) value of 33 J/gK without adding any flame retardants. Based on its outstanding capability of carbon formation, this newly obtained benzoxazine resin was carbonized and activated to obtain a porous carbon material doped with both sulfur and nitrogen. The CO absorption of the carbon material at 0 °C and 25 °C at 1 bar was 3.64 mmol/g and 3.26 mmol/g, respectively. The above excellent comprehensive properties prove its potential applications in many advanced fields.
Topics: Benzoxazines; Spectroscopy, Fourier Transform Infrared; Carbon; Polymerization
PubMed: 37446739
DOI: 10.3390/molecules28135077 -
The Science of the Total Environment Dec 2023Membrane fouling is a major challenge which limits the sustainable application of membrane filtration-based microalgal harvesting at industrial level. Membrane fouling... (Review)
Review
Membrane fouling is a major challenge which limits the sustainable application of membrane filtration-based microalgal harvesting at industrial level. Membrane fouling leads to increased operational and maintenance costs and represents a major obstacle to microalgal downstream processing. Nano-clays are promising naturally occurring nanoparticles in membrane fabrication due to their low-cost, facile preparation, and their superior properties in terms of surface hydrophilicity, mechanical stability, and resistance against chemicals. The membrane surface modification using nano-clays is a sustainable promising approach to improve membranes mechanical properties and their fouling resistance. However, the positive effects of nano-clay particles on membrane fouling are often limited by aggregation and poor adhesion to the base polymeric matrix. This review surveys the recent efforts to achieve anti-fouling behavior using membrane surface modification with nano-clay fillers. Further, strategies to achieve a better incorporation of nano-clay in the polymer matrix of the membrane are summarised, and the factors that govern the membrane fouling, stability, adhesion, agglomeration and leaching are discussed in depth.
Topics: Clay; Microalgae; Biofouling; Membranes, Artificial; Filtration; Polymers
PubMed: 37611702
DOI: 10.1016/j.scitotenv.2023.166479 -
Molecules (Basel, Switzerland) Oct 2023Nucleoside analogs play a crucial role in the production of high-value antitumor and antimicrobial drugs. Currently, nucleoside analogs are mainly obtained through... (Review)
Review
Nucleoside analogs play a crucial role in the production of high-value antitumor and antimicrobial drugs. Currently, nucleoside analogs are mainly obtained through nucleic acid degradation, chemical synthesis, and biotransformation. However, these methods face several challenges, such as low concentration of the main product, the presence of complex matrices, and the generation of numerous by-products that significantly limit the development of new drugs and their pharmacological studies. Therefore, this work aims to summarize the universal separation methods of nucleoside analogs, including crystallization, high-performance liquid chromatography (HPLC), column chromatography, solvent extraction, and adsorption. The review also explores the application of molecular imprinting techniques (MITs) in enhancing the identification of the separation process. It compares existing studies reported on adsorbents of molecularly imprinted polymers (MIPs) for the separation of nucleoside analogs. The development of new methods for selective separation and purification of nucleosides is vital to improving the efficiency and quality of nucleoside production. It enables us to obtain nucleoside products that are essential for the development of antitumor and antiviral drugs. Additionally, these methods possess immense potential in the prevention and control of serious diseases, offering significant economic, social, and scientific benefits to the fields of environment, biomedical research, and clinical therapeutics.
Topics: Nucleosides; Polymers; Molecular Imprinting; Molecularly Imprinted Polymers; Chromatography, High Pressure Liquid; Adsorption; Solid Phase Extraction
PubMed: 37894522
DOI: 10.3390/molecules28207043 -
Biomaterials Science Nov 2023Fimbriae are long filamentous polymeric protein structures located upon the surface of bacteria. Often implicated in pathogenicity, the biosynthesis and function of... (Review)
Review
Fimbriae are long filamentous polymeric protein structures located upon the surface of bacteria. Often implicated in pathogenicity, the biosynthesis and function of fimbriae has been a productive topic of study for many decades. Evolutionary pressures have ensured that fimbriae possess unique structural and mechanical properties which are advantageous to bacteria. These properties are also difficult to engineer with well-known synthetic and natural fibres, and this has raised an intriguing question: can we exploit the unique properties of bacterial fimbriae in useful ways? Initial work has set out to explore this question by using Capsular antigen fragment 1 (Caf1), a fimbriae expressed naturally by . These fibres have evolved to 'shield' the bacterium from the immune system of an infected host, and thus are rather bioinert in nature. Caf1 is, however, very amenable to structural mutagenesis which allows the incorporation of useful bioactive functions and the modulation of the fibre's mechanical properties. Its high-yielding recombinant synthesis also ensures plentiful quantities of polymer are available to drive development. These advantageous features make Caf1 an archetype for the development of new polymers and materials based upon bacterial fimbriae. Here, we cover recent advances in this new field, and look to future possibilities of this promising biopolymer.
Topics: Antigens, Bacterial; Bacterial Proteins; Fimbriae, Bacterial; Polymers; Materials Science; Yersinia pestis
PubMed: 37791425
DOI: 10.1039/d3bm01075a -
The EMBO Journal Dec 2023Tunnelling nanotubes (TNTs) connect distant cells and mediate cargo transfer for intercellular communication in physiological and pathological contexts. How cells...
Tunnelling nanotubes (TNTs) connect distant cells and mediate cargo transfer for intercellular communication in physiological and pathological contexts. How cells generate these actin-mediated protrusions to span lengths beyond those attainable by canonical filopodia remains unknown. Through a combination of micropatterning, microscopy, and optical tweezer-based approaches, we demonstrate that TNTs formed through the outward extension of actin achieve distances greater than the mean length of filopodia and that branched Arp2/3-dependent pathways attenuate the extent to which actin polymerizes in nanotubes, thus limiting their occurrence. Proteomic analysis using epidermal growth factor receptor kinase substrate 8 (Eps8) as a positive effector of TNTs showed that, upon Arp2/3 inhibition, proteins enhancing filament turnover and depolymerization were reduced and Eps8 instead exhibited heightened interactions with the inverted Bin/Amphiphysin/Rvs (I-BAR) domain protein IRSp53 that provides a direct connection with linear actin polymerases. Our data reveals how common protrusion players (Eps8 and IRSp53) form tunnelling nanotubes, and that when competing pathways overutilizing such proteins and monomeric actin in Arp2/3 networks are inhibited, processes promoting linear actin growth dominate to favour tunnelling nanotube formation.
Topics: Actins; Polymerization; Proteomics; Nanotubes; Actin Cytoskeleton
PubMed: 38009333
DOI: 10.15252/embj.2023113761 -
International Journal of Molecular... Aug 2023Different techniques have been developed to overcome the recalcitrant nature of lignocellulosic biomass and extract lignin biopolymer. Lignin has gained considerable... (Review)
Review
Different techniques have been developed to overcome the recalcitrant nature of lignocellulosic biomass and extract lignin biopolymer. Lignin has gained considerable interest owing to its attractive properties. These properties may be more beneficial when including lignin in the preparation of highly desired value-added products, including hydrogels. Lignin biopolymer, as one of the three major components of lignocellulosic biomaterials, has attracted significant interest in the biomedical field due to its biocompatibility, biodegradability, and antioxidant and antimicrobial activities. Its valorization by developing new hydrogels has increased in recent years. Furthermore, lignin-based hydrogels have shown great potential for various biomedical applications, and their copolymerization with other polymers and biopolymers further expands their possibilities. In this regard, lignin-based hydrogels can be synthesized by a variety of methods, including but not limited to interpenetrating polymer networks and polymerization, crosslinking copolymerization, crosslinking grafted lignin and monomers, atom transfer radical polymerization, and reversible addition-fragmentation transfer polymerization. As an example, the crosslinking mechanism of lignin-chitosan-poly(vinyl alcohol) (PVA) hydrogel involves active groups of lignin such as hydroxyl, carboxyl, and sulfonic groups that can form hydrogen bonds (with groups in the chemical structures of chitosan and/or PVA) and ionic bonds (with groups in the chemical structures of chitosan and/or PVA). The aim of this review paper is to provide a comprehensive overview of lignin-based hydrogels and their applications, focusing on the preparation and properties of lignin-based hydrogels and the biomedical applications of these hydrogels. In addition, we explore their potential in wound healing, drug delivery systems, and 3D bioprinting, showcasing the unique properties of lignin-based hydrogels that enable their successful utilization in these areas. Finally, we discuss future trends in the field and draw conclusions based on the findings presented.
Topics: Lignin; Biomass; Chitosan; Antioxidants; Hydrogels; Polymers
PubMed: 37686299
DOI: 10.3390/ijms241713493