-
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 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 -
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 -
Applied Microbiology and Biotechnology Aug 2016Poly(ɛ-L-lysine) (ɛ-PL) is an unusual biopolymer composed of L-lysine connected between α-carboxyl and ɛ-amino groups. It has been used as a preservative in food and... (Review)
Review
Poly(ɛ-L-lysine) (ɛ-PL) is an unusual biopolymer composed of L-lysine connected between α-carboxyl and ɛ-amino groups. It has been used as a preservative in food and cosmetics industries, drug carrier in medicines, and gene carrier in gene therapy. Modern biotechnology has significantly improved the synthetic efficiency of this novel homopoly(amino acid) on an industrial scale and has expanded its industrial applications. In the latest years, studies have focused on the biotechnological production and understanding the biosynthetic mechanism of microbial ɛ-PL. Herein, this review focuses on the current trends and future perspectives of microbial ɛ-PL. Information on the screening of ɛ-PL-producing strains, fermentative production of ɛ-PL, breeding of high-ɛ-PL-producing strains, genomic data of ɛ-PL-producing strains, biosynthetic mechanism of microbial ɛ-PL, and the control of molecular weight of microbial ɛ-PL is included. This review will contribute to the development of this novel homopoly(amino acid) and serve as a basis of studies on other biopolymers.
Topics: Biopolymers; Bioreactors; Biotechnology; Cosmetics; Drug Carriers; Fermentation; Food Preservatives; Polylysine; Streptomyces
PubMed: 27333910
DOI: 10.1007/s00253-016-7677-3 -
Biomaterials Science Dec 2020Infections related to implanted medical devices have placed a heavy burden on public health and require feasible solutions. In this study, a simple approach is reported...
Infections related to implanted medical devices have placed a heavy burden on public health and require feasible solutions. In this study, a simple approach is reported to fabricate an antifouling and antibacterial dual-functional coating. One-step aqueous supramolecular assembly of bovine serum albumin (BSA) is employed to immobilize ε-polylysine (ε-PL) and form a coating (PTB@ε-PL). Based on amyloid-like protein aggregation through the rapid reduction of the intramolecular disulfide bonds of BSA by tris(2-carboxyethyl) phosphine, a dense PTB@ε-PL nanofilm with controllable thickness and ε-PL loading density can be covered on virtually arbitrary material surfaces by simple aqueous dipping. In vitro and in vivo experiments show that this coating not only exhibits effective antibacterial activity against Gram-positive/Gram-negative bacteria, but also imparts excellent antifouling property to the surface. As a pure biopolymer coating, the PTB@ε-PL nanofilm shows negligible cytotoxicity and hemolysis. In addition, due to the various functional groups exposed on the surface of the nanofilm, the coating shows excellent interfacial bonding stability and can maintain bactericidal and antifouling properties under harsh conditions including ultrasound, autoclaving, organic solvents, and physiological body fluids.
Topics: Anti-Bacterial Agents; Anti-Infective Agents; Polylysine; Protein Aggregates; Serum Albumin, Bovine
PubMed: 32691767
DOI: 10.1039/d0bm00760a -
International Journal of Biological... Mar 2024ε-Poly-l-lysine (ε-PL) is a natural homo-poly(amino acid) which can be produced by microorganisms. With the advantages in broad-spectrum antimicrobial activity,... (Review)
Review
ε-Poly-l-lysine (ε-PL) is a natural homo-poly(amino acid) which can be produced by microorganisms. With the advantages in broad-spectrum antimicrobial activity, biodegradability, and biocompatibility, ε-PL has been widely used as a preservative in the food industry. Different molecular architectures endow ε-PL and ε-PL-based materials with versatile applications. However, the microbial synthesis of ε-PL is currently limited by low efficiencies in genetic engineering and molecular architecture modification. This review presents recent advances in ε-PL production and molecular architecture modification of microbial ε-PL, with a focus on the current challenges and solutions for the improvement of the productivity and diversity of ε-PL. In addition, we highlight recent examples where ε-PL has been applied to expand the versability of edible films and nanoparticles in various applications. Commercial production and the challenges and future research directions in ε-PL biosynthesis are also discussed. Currently, although the main use of ε-PL is as a food preservative, ε-PL and ε-PL-based polymers have shown excellent application potential in biomedical fields. With the development of synthetic biology, the design and synthesis of ε-PL with a customized molecular architecture are possible in the near future. ε-PL-based polymers with specific functions will be a new trend in biopolymer manufacturing.
Topics: Polylysine; Streptomyces; Fermentation; Amino Acids; Polymers
PubMed: 38262828
DOI: 10.1016/j.ijbiomac.2024.129513 -
Biomacromolecules Aug 2017After more than 20 years of intensive investigations, gene therapy has become one of the most promising strategies for treating genetic diseases. However, the lack of... (Review)
Review
After more than 20 years of intensive investigations, gene therapy has become one of the most promising strategies for treating genetic diseases. However, the lack of ideal delivery systems has limited the clinical realization of gene therapy's tremendous potential, especially for DNA-based gene therapy. Over the past decade, considerable advances have been made in the application of polymer-based DNA delivery systems for gene therapy, especially through multifunctional systems. The core concept behind multifunctional polymeric DNA delivery systems is to endow one single DNA carrier, via materials engineering and surface modification, with several active functions, e.g., good cargo DNA protection, excellent colloidal stability, high cellular uptake efficiency, efficient endo/lysosome escape, effective import into the nucleus, and DNA unpacking. Such specially developed vectors would be capable of overcoming multiple barriers to the successful delivery of DNA. In this review, we first provide a comprehensive overview of the interactions between the protein corona and DNA vectors, the mechanisms and challenges of nonviral DNA vectors, and important concepts in the design of DNA carriers identified via past reports on DNA delivery systems. Finally, we highlight and discuss recent advances in multifunctional polymeric DNA delivery systems based on "off-the-shelf" polycations including polyethylenimine (PEI), poly-l-lysine (PLL), and chitosan and offer perspectives on future developments.
Topics: Animals; DNA; Drug Carriers; Gene Transfer Techniques; Humans; Polyethyleneimine; Polylysine
PubMed: 28661127
DOI: 10.1021/acs.biomac.7b00803 -
Journal of Food Protection Jul 2023The purpose of the study was to investigate the mechanism of inactivation of Serratia liquefaciens by different treatments, namely corona discharge plasma (CDP),...
The purpose of the study was to investigate the mechanism of inactivation of Serratia liquefaciens by different treatments, namely corona discharge plasma (CDP), ε-polylysine (ε-PL), and corona discharge plasma combined with ε-polylysine (CDP plus ε-PL). The results showed that the combined treatment of CDP and ε-PL exhibited significant antibacterial effects. The total number of colonies of S. liquefaciens dropped by 0.49 log CFU/mL following 4 min of CDP treatment, 4MIC ε-PL treatment for 6 h alone decreased the amounts of colonies by 2.11 log CFU/mL, and 6 h of treatment with 4MIC ε-PL after the bacterium was treated with CDP could decrease the number of colonies by 6.77 log CFU/mL. Scanning electron microscopy images showed that the combined treatment of CDP and ε-PL caused the most serious damage to the cell morphology. Electrical conductivity, nucleic acid, and PI staining indicated that the combined treatment dramatically enhanced the permeability of the cell membrane. In addition, the combined treatment led to a significant decrease in SOD and POD enzyme activities in S. liquefaciens, which prevented energy metabolism. Finally, the determination of free and intracellular ε-PL concentrations confirmed that the treatment of CDP could cause the bacteria to bind more ε-PL and exert more significant bacterial inhibition. Therefore, CDP and ε-PL had a synergistic effect in the inhibition of S. liquefaciens.
Topics: Polylysine; Serratia liquefaciens; Anti-Bacterial Agents; Cell Membrane; Microscopy, Electron, Scanning
PubMed: 37295216
DOI: 10.1016/j.jfp.2023.100078 -
Stem Cell Reports Nov 2017Engineering of biomaterials with specific biological properties has gained momentum as a means to control stem cell behavior. Here, we address the effect of...
Engineering of biomaterials with specific biological properties has gained momentum as a means to control stem cell behavior. Here, we address the effect of bifunctionalized hydrogels comprising polylysine (PL) and a 19-mer peptide containing the laminin motif IKVAV (IKVAV) on embryonic and adult neuronal progenitor cells under different stiffness regimes. Neuronal differentiation of embryonic and adult neural progenitors was accelerated by adjusting the gel stiffness to 2 kPa and 20 kPa, respectively. While gels containing IKVAV or PL alone failed to support long-term cell adhesion, in bifunctional gels, IKVAV synergized with PL to promote differentiation and formation of focal adhesions containing β-integrin in embryonic cortical neurons. Furthermore, in adult neural stem cell culture, bifunctionalized gels promoted neurogenesis via the expansion of neurogenic clones. These data highlight the potential of synthetic matrices to steer stem and progenitor cell behavior via defined mechano-adhesive properties.
Topics: Animals; Cells, Cultured; Elasticity; Focal Adhesions; Hydrogels; Laminin; Mice; Mice, Inbred C57BL; Mouse Embryonic Stem Cells; Neural Stem Cells; Neurogenesis; Peptide Fragments; Polylysine; Tissue Engineering
PubMed: 28988991
DOI: 10.1016/j.stemcr.2017.09.002 -
ACS Applied Materials & Interfaces Oct 2023The choice of the antimicrobial agent and finishing process is very important for the activity, durability, and safety of antimicrobial fabrics. Here, a novel...
The choice of the antimicrobial agent and finishing process is very important for the activity, durability, and safety of antimicrobial fabrics. Here, a novel antimicrobial cotton fabric (HPL-CF) was constructed by covalently bonding an antimicrobial agent, hyperbranched polylysine (HPL), onto the surface of a cotton fabric (CF) pretreated with a silane coupling agent, 3-chloropropyltrimethoxysilane (CPTMS). The multiple amino groups contained in the periphery of HPL make it possible to react with the CF to form multiple bonds, which is beneficial to improve the durability and safety of HPL-CFs. The obtained HPL-CFs exhibited excellent antimicrobial activities against (, Gram-negative bacteria), (, Gram-positive bacteria), and (, fungi) even when the CF was treated with HPL solution at the concentration of 0.5 wt %. HPL-CFs maintained 98, >99, and >99% of antimicrobial ratios for , , and , respectively, after 50 equiv of domestic laundering cycles, surpassing the requirements of the AAA class. The halo method, cell compatibility, and skin irritation assays all prove the fine safety of HPL-CFs. This work demonstrates the great advantages of applying HPL in the antimicrobial finishing of fabrics.
Topics: Polylysine; Cotton Fiber; Escherichia coli; Staphylococcus aureus; Metal Nanoparticles; Anti-Infective Agents; Candida albicans; Anti-Bacterial Agents
PubMed: 37792694
DOI: 10.1021/acsami.3c10587