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International Journal of Biological... Nov 2023The ε-polylysine (ε-PL) is a food-grade antimicrobial substance. The cationic ε-PL molecules may interact with anionic components of food matrix causing turbidity,...
The ε-polylysine (ε-PL) is a food-grade antimicrobial substance. The cationic ε-PL molecules may interact with anionic components of food matrix causing turbidity, sedimentation, and hampering the antimicrobial activity. Herein, sodium alginate (SA) was used as wall material to encapsulate ε-PL, thereby to synthesize ε-PL-SA nanoparticles (ε-PL-SA-NPs). Monosaccharide composition and molecular weight of SA were characterized. The synthetic scheme is optimized and physicochemical characteristics and antimicrobial potential was investigated. Findings indicate that SA primarily consisted of mannuronic acid (95.25 %), weight average molecular weight (Mw) of SA was 176.464 kDa, and the molecular configuration of SA was irregular line clusters. The encapsulation efficiency (EE) of ε-PL in ε-PL-SA-NPs made under optimum strategy (at pH 6.0, mass ratio of ε-PL to SA is 0.14, and SA concentration is 6 mg/mL) is about 99.74 %. The particle size of ε-PL-SA-NPs is ∼541.86 nm. The SEM image showed that the ε-PL-SA-NPs had a nearly spherical morphology. Zeta-potential and FTIR data reveal the interaction between ε-PL and SA was electrostatic and the hydrogen bonding. Agar diffusion assay exhibit that ε-PL-SA-NPs had antimicrobial activity against Escherichia coli and Staphylococcus aureus. The salmon preservation experiments reveal sustained antimicrobial efficacy of ε-PL-SA-NPs.
Topics: Alginates; Polylysine; Nanoparticles; Particle Size; Anti-Infective Agents; Staphylococcus aureus; Molecular Weight; Escherichia coli; Anti-Bacterial Agents; Microbial Sensitivity Tests; Drug Carriers
PubMed: 37595718
DOI: 10.1016/j.ijbiomac.2023.126329 -
International Journal of Molecular... Jan 2022Liver cancer is currently regarded as the second leading cause of cancer-related mortality globally and is the sixth most diagnosed malignancy. Selenium nanoparticles...
Liver cancer is currently regarded as the second leading cause of cancer-related mortality globally and is the sixth most diagnosed malignancy. Selenium nanoparticles (SeNPs) have attracted favorable attention as nanocarriers for gene therapy, as they possess beneficial antioxidant and anticancer properties. This study aimed to design, functionalize and characterize SeNPs to efficiently bind, protect and deliver pCMV- DNA to hepatocellular carcinoma (HepG2) cells. The SeNPs were synthesized by ascorbic acid reduction and functionalized with poly-L-lysine (PLL) to stabilize and confer positive charges to the nanoparticles. The SeNPs were further decorated with lactobionic acid (LA) to target the asialoglycoprotein receptors abundantly expressed on the surface of the hepatocytes. All SeNPs were spherical, in the nanoscale range (<130 nm) and were capable of successfully binding, compacting and protecting the pDNA against nuclease degradation. The functionalized SeNP nanocomplexes exhibited minimal cytotoxicity (<30%) with enhanced transfection efficiency in the cell lines tested. Furthermore, the targeted SeNP (LA-PLL-SeNP) nanocomplex showed significant (* < 0.05, ** < 0.01, **** < 0.0001) transgene expression in the HepG2 cells compared to the receptor-negative embryonic kidney (HEK293) cells, confirming receptor-mediated endocytosis. Overall, these functionalized SeNPs exhibit favorable features of suitable gene nanocarriers for the treatment of liver cancer.
Topics: Disaccharides; Gene Transfer Techniques; HEK293 Cells; HeLa Cells; Hep G2 Cells; Humans; Liver; Metal Nanoparticles; Polylysine; Selenium
PubMed: 35163414
DOI: 10.3390/ijms23031492 -
Applied and Environmental Microbiology Oct 2022ε-Poly-l-lysine (ε-PL) is a wide-spectrum antimicrobial agent, while its biosynthesis-inducing signals are rarely reported. This study found that Botrytis cinerea...
ε-Poly-l-lysine (ε-PL) is a wide-spectrum antimicrobial agent, while its biosynthesis-inducing signals are rarely reported. This study found that Botrytis cinerea extracts could act as a microbial call to induce a physiological modification of Streptomyces albulus for ε-PL efficient biosynthesis and thereby resulted in ε-PL production (34.2 g/liter) 1.34-fold higher than control. The elicitors could be primary isolated by ethanol and butanol extraction, which resulted in more vibrant, aggregate and stronger mycelia. The elicitor-derived physiological changes focused on three aspects: ε-PL synthase, energy metabolism, and lysine biosynthesis. After elicitor addition, upregulated sigma factor and improved transcription and expression of directly contributed to the high ε-PL productivity; upregulated genes in tricarboxylic acid (TCA) cycle and energy metabolism promoted activities of citrate synthase and the electron transport system; in addition, pool enlargements of ATP, ADP, and NADH guaranteed the ATP provision for ε-PL assembly. Lysine biosynthesis was also increased based on enhancements of gene transcription, key enzyme activities, and intracellular metabolite pools related to carbon source utilization, the Embden-Meyerhof pathway (EMP), the diaminopimelic acid pathway (DAP), and the replenishment pathway. Interestingly, the elicitors stimulated the gene transcription for the quorum-sensing system and resulted in upregulation of genes for other antibiotic production. These results indicated that the Botrytis cinerea could produce inducing signals to change the Streptomyces mycelial physiology and accelerate the ε-PL biosynthesis. This work identified the role of microbial elicitors on ε-PL production and disclosed the underlying mechanism through analysis of gene transcription, key enzyme activities, and intracellular metabolite pools, including transcriptome and metabolome analysis. It was the first report for the inducing effects of the "microbial call" to Streptomyces albulus and ε-PL biosynthesis, and these elicitors could be potentially obtained from decayed fruits infected by Botrytis cinerea; hence, this may be a way of turning a biohazard into bioproduct wealth. This study provided a reference for application of microbial signals in secondary metabolite production, which is of theoretical and practical significance in industrial antibiotic production.
Topics: Adenosine Diphosphate; Adenosine Triphosphate; Anti-Bacterial Agents; Butanols; Carbon; Citrate (si)-Synthase; Diaminopimelic Acid; Ethanol; Fermentation; Hazardous Substances; Metabolome; NAD; Polylysine; Sigma Factor; Transcriptome; Tricarboxylic Acids
PubMed: 36190251
DOI: 10.1128/aem.00952-22 -
Science Bulletin May 2024Adequate drug delivery across the blood-brain barrier (BBB) is a critical factor in treating central nervous system (CNS) disorders. Inspired by swimming fish and the...
Adequate drug delivery across the blood-brain barrier (BBB) is a critical factor in treating central nervous system (CNS) disorders. Inspired by swimming fish and the microstructure of the nasal cavity, this study is the first to develop swimming short fibrous nasal drops that can directly target the nasal mucosa and swim in the nasal cavity, which can effectively deliver drugs to the brain. Briefly, swimming short fibrous nasal drops with charged controlled drug release were fabricated by electrospinning, homogenization, the π-π conjugation between indole group of fibers, the benzene ring of leucine-rich repeat kinase 2 (LRRK2) inhibitor along with charge-dipole interaction between positively charged poly-lysine (PLL) and negatively charged surface of fibers; this enabled these fibers to stick to nasal mucosa, prolonged the residence time on mucosa, and prevented rapid mucociliary clearance. In vitro, swimming short fibrous nasal drops were biocompatible and inhibited microglial activation by releasing an LRRK2 inhibitor. In vivo, luciferase-labelled swimming short fibrous nasal drops delivered an LRRK2 inhibitor to the brain through the nasal mucosa, alleviating cognitive dysfunction caused by sepsis-associated encephalopathy by inhibiting microglial inflammation and improving synaptic plasticity. Thus, swimming short fibrous nasal drops is a promising strategy for the treatment of CNS diseases.
Topics: Animals; Administration, Intranasal; Nasal Mucosa; Blood-Brain Barrier; Drug Delivery Systems; Mice; Nasal Cavity; Polylysine; Swimming; Male; Brain; Mucociliary Clearance; Microglia; Humans
PubMed: 38522998
DOI: 10.1016/j.scib.2024.03.013 -
Journal of Experimental & Clinical... Jun 2021Immunotherapy is currently under intensive investigation as a potential breakthrough treatment option for glioblastoma. Given the anatomical and immunological... (Review)
Review
Immunotherapy is currently under intensive investigation as a potential breakthrough treatment option for glioblastoma. Given the anatomical and immunological complexities surrounding glioblastoma, lymphocytes that infiltrate the brain to develop durable immunity with memory will be key. Polyinosinic:polycytidylic acid, or poly(I:C), and its derivative poly-ICLC could serve as a priming or boosting therapy to unleash lymphocytes and other factors in the (immuno)therapeutic armory against glioblastoma. Here, we present a systematic review on the effects and efficacy of poly(I:C)/poly-ICLC for glioblastoma treatment, ranging from preclinical work on cellular and murine glioblastoma models to reported and ongoing clinical studies. MEDLINE was searched until 15 May 2021 to identify preclinical (glioblastoma cells, murine models) and clinical studies that investigated poly(I:C) or poly-ICLC in glioblastoma. A systematic review approach was conducted according to PRISMA guidelines. ClinicalTrials.gov was queried for ongoing clinical studies. Direct pro-tumorigenic effects of poly(I:C) on glioblastoma cells have not been described. On the contrary, poly(I:C) changes the immunological profile of glioblastoma cells and can also kill them directly. In murine glioblastoma models, poly(I:C) has shown therapeutic relevance as an adjuvant therapy to several treatment modalities, including vaccination and immune checkpoint blockade. Clinically, mostly as an adjuvant to dendritic cell or peptide vaccines, poly-ICLC has been demonstrated to be safe and capable of eliciting immunological activity to boost therapeutic responses. Poly-ICLC could be a valuable tool to enhance immunotherapeutic approaches for glioblastoma. We conclude by proposing several promising combination strategies that might advance glioblastoma immunotherapy and discuss key pre-clinical aspects to improve clinical translation.
Topics: Animals; Brain Neoplasms; Cancer Vaccines; Carboxymethylcellulose Sodium; Clinical Trials as Topic; Glioblastoma; Humans; Immune Checkpoint Inhibitors; Immunotherapy; Mice; Poly I-C; Polylysine
PubMed: 34172082
DOI: 10.1186/s13046-021-02017-2 -
Scientific Reports Jul 2020Antimicrobial peptides (AMPs) are components of immune defense in many organisms, including plants. They combat pathogens due to their antiviral, antifungal and...
Antimicrobial peptides (AMPs) are components of immune defense in many organisms, including plants. They combat pathogens due to their antiviral, antifungal and antibacterial properties, and are considered potential therapeutic agents. An example of AMP is Epsilon-Poly-L-lysine (EPL), a polypeptide formed by ~ 25 lysine residues with known antimicrobial activity against several human microbial pathogens. EPL presents some advantages such as good water solubility, thermal stability, biodegradability, and low toxicity, being a candidate for the control of phytopathogens. Our aim was to evaluate the antimicrobial activity of EPL against four phytobacterial species spanning different classes within the Gram-negative phylum Proteobacteria: Agrobacterium tumefaciens (syn. Rhizobium radiobacter), Ralstonia solanacearum, Xanthomonas citri subsp. citri (X. citri), and Xanthomonas euvesicatoria. The minimum inhibitory concentration (MIC) of the peptide ranged from 80 μg/ml for X. citri to 600 μg/ml for R. solanacearum and X. euvesicatoria. Two hours of MIC exposure led to pathogen death due to cell lysis and was enough for pathogen clearance. The protective and curative effects of EPL were demonstrated on tomato plants inoculated with X. euvesicatoria. Plants showed less disease severity when sprayed with EPL solution, making it a promising natural product for the control of plant diseases caused by diverse Proteobacteria.
Topics: Anti-Bacterial Agents; Gram-Negative Bacteria; Solanum lycopersicum; Plant Diseases; Polylysine
PubMed: 32647256
DOI: 10.1038/s41598-020-68262-1 -
Food Chemistry Mar 2022Three edible food packaging films loaded with perillaldehyde (P), thymol (T), or ɛ-polylysine (ɛ-PL) in gelatin/zein (G/Z) nanofibers were prepared and characterized....
Preparation and characterization of gelatin/zein nanofiber films loaded with perillaldehyde, thymol, or ɛ-polylysine and evaluation of their effects on the preservation of chilled chicken breast.
Three edible food packaging films loaded with perillaldehyde (P), thymol (T), or ɛ-polylysine (ɛ-PL) in gelatin/zein (G/Z) nanofibers were prepared and characterized. Their effects on the preservation of chilled chicken breast were evaluated. Results showed that the addition of perillaldehyde, thymol, and ɛ-polylysine improved the morphology and diameter of the G/Z. Loading with perillaldehyde improved the elongation and tensile strength of the G/Z/P by 18% and 55%, respectively. The water vapor permeability and oxygen permeability of the G/Z/P were lower than those of the G/Z/T and G/Z/ɛ-PL. X-ray diffraction, differential scanning calorimetry suggested that perillaldehyde enhanced the thermal stability of the G/Z/P. Measurements of 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), total volatile basic nitrogen, and total viable bacterial counts demonstrated that the G/Z/P had good bio-compatibility and effectively prolonged the shelf life of chilled chicken breasts by over 6 days. Therefore, the G/Z/P developed herein has potential application in chilled meat packaging.
Topics: Animals; Chickens; Food Packaging; Food Preservation; Gelatin; Meat; Monoterpenes; Nanofibers; Permeability; Polylysine; Tensile Strength; Thymol; Zein
PubMed: 34717090
DOI: 10.1016/j.foodchem.2021.131439 -
Journal of the Mechanical Behavior of... Sep 2023The aim was to quantify effects of polylysine (PLS, 2 or 5 wt%) and monocalcium phosphate (MCP, 4 or 8 wt%) on properties of dental composites.
OBJECTIVES
The aim was to quantify effects of polylysine (PLS, 2 or 5 wt%) and monocalcium phosphate (MCP, 4 or 8 wt%) on properties of dental composites.
METHODS
Light-activated, lower surface polymerisation kinetics versus sample depth (1-4 mm) of 4 formulations were quantified using ATR-FTIR. Water sorption and solubility (at 1 week) were assessed following ISO/4049. PLS release (over 1 month) and biaxial flexural strength (over 6 months) of fully-cured, water-immersed, 1 mm thick discs were determined. Surface mineral precipitation, following immersion in simulated body fluid (SBF), was assessed by SEM. Z250 was used as a conventional composite comparator.
RESULTS
With 40s light exposure, increasing depth (from 1 to 4 mm) led to enhanced delay before polymerisation (from 3 to 17s) and decreased final conversion (72-66%) irrespective of PLS and MCP level. Increasing PLS and MCP raised solubility (4-13 μg/mm). Water sorption (between 32 and 55 μg/mm) and final PLS release (8-13% of disc content) were raised primarily by increasing PLS. Higher PLS also reduced strength. Strength reached minimum values (69-94 MPa) at 3 months. Surface mineral deposition was enhanced by increased MCP. For Z250, polymerisation delays (3-6s) and final conversions (55-54%) at 1-4 mm depth, solubility (0 μg/mm), water sorption (16 μg/mm) and strength (180 MPa) were all significantly different.
CONCLUSION
Delay time increased whilst final conversion decreased with thicker samples. Higher PLS enhances its percentage release, but lower level is required to keep water sorption, solubility and mechanical properties within ISO 4049 recommendations. Doubling MCP raises solubility and enhances minerals reprecipitation with minimal mechanical property compromise.
Topics: Polylysine; Composite Resins; Materials Testing; Solubility; Phosphates; Water; Surface Properties; Dental Materials
PubMed: 37499523
DOI: 10.1016/j.jmbbm.2023.106039 -
ACS Biomaterials Science & Engineering Feb 2022The steady development of bacterial resistance has become a global public health issue, and new antibacterial agents that are active against drug-resistant bacteria and...
The steady development of bacterial resistance has become a global public health issue, and new antibacterial agents that are active against drug-resistant bacteria and less susceptible to bacterial resistance are urgently needed. Here, a series of low-molecular-weight cationic polylysines (C-PLL) with different hydrophobic end groups (C) and degrees of polymerization (PLL) was synthesized and used in antibacterial applications. All the obtained C-PLL have antibacterial activity. Among them, C-PLL displays the best antibacterial effect for Gram-positive bacteria, that is, () and methicillin-resistant (MRSA), and highest selectivity against Gram-positive bacteria. A mechanistic study revealed that the C-PLL destroys the integrity of the bacterial cell membrane and causes effective bacterial death. Owing to this membrane-disrupting property, C-PLL showed rapid bacterial killing kinetics and was not likely to develop resistance after repeat treatment (up to 13 generations). Moreover, C-PLL demonstrated a significant therapeutic effect on an MRSA infection mouse model, which further proved that this synthetic polymer could be used as an effective weapon against bacterial infections.
Topics: Animals; Anti-Bacterial Agents; Hemolysis; Methicillin-Resistant Staphylococcus aureus; Mice; Microbial Sensitivity Tests; Polylysine; Staphylococcus aureus
PubMed: 35050580
DOI: 10.1021/acsbiomaterials.1c01527 -
International Journal of Biological... May 2022The design of multifunctional hydrogels based on bioactive hyaluronic acid (HA) and antibacterial cationic polymer ɛ-poly-l-lysine (ε-PL) is a promising tool in tissue...
The design of multifunctional hydrogels based on bioactive hyaluronic acid (HA) and antibacterial cationic polymer ɛ-poly-l-lysine (ε-PL) is a promising tool in tissue engineering applications. In the current study, we have designed hyaluronic acid and ɛ-polylysine composite hydrogel systems with antibacterial and cell attractive properties. Two distinct crosslinking approaches were used: the physical crosslinking based on electrostatic attractions and the chemical crosslinking of charged functional groups (-NH and -COOH). The impact of the crosslinking strategy on fabricated hydrogel molecular structure, swelling behavior, gel fraction, morphology, porosity, viscoelastic properties, antibacterial activity, and in vitro biocompatibility was evaluated. Both chemically and physically crosslinked HA/ԑ-PL hydrogels demonstrated fast swelling behavior and long-term stability for at least 28 days, as well as similar order of stiffness (10-30 kPa). We demonstrated that physically crosslinked hydrogels inhibited over 99.999% of Gram-negative E. coli, while chemically crosslinking strategy led to the antibacterial efficiency decrease. However, cell viability was significantly improved, confirming the importance of the applied crosslinking approach to the antibacterial activity and in vitro biocompatibility. The distinct differences in the physicochemical and biological properties of the developed materials provide new opportunities to design next-generation functional composite hydrogel systems.
Topics: Anti-Bacterial Agents; Escherichia coli; Hyaluronic Acid; Hydrogels; Polylysine
PubMed: 35378161
DOI: 10.1016/j.ijbiomac.2022.03.207