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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 -
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 -
Biomedicine & Pharmacotherapy =... Jun 2023Drug delivery systems require that carrier materials have good biocompatibility, degradability, and constructability. Poly(amino acids), a substance with a distinctive...
Drug delivery systems require that carrier materials have good biocompatibility, degradability, and constructability. Poly(amino acids), a substance with a distinctive secondary structure, not only have the basic features of the carrier materials but also have several reactive functional groups in the side chain, which can be employed as drug carriers to deliver anticancer drugs. The conformation of isomers of drug carriers has some influence on the preparation, morphology, and efficacy of nanoparticles. In this study, two isomers of polylysine, including ε-polylysine (ε-PL) and α-polylysine (α-PL), were used as drug carriers to entrap methotrexate (MTX) and construct nano-drug delivery systems. ε-PL/MTX nanoparticles with the morphology of helical nanorods presented a small particle size (115.0 nm), and relative high drug loading content (57.8 %). The anticancer effect of ε-PL/MTX nanoparticles was 1.3-fold and 2.6-fold stronger than that of α-PL/MTX nanoparticles in vivo and in vitro, respectively. ε-PL is an ideal drug carrier with potential clinical application prospects.
Topics: Methotrexate; Polylysine; Antineoplastic Agents; Drug Carriers; Nanoparticles
PubMed: 37037095
DOI: 10.1016/j.biopha.2023.114662 -
Journal of Nanobiotechnology Aug 2022Developing highly efficient pharmaceuticals to eradicate pathogens and facilitate wound healing is of great concern. Despite some cationic carbon dots (CDs) have been...
Developing highly efficient pharmaceuticals to eradicate pathogens and facilitate wound healing is of great concern. Despite some cationic carbon dots (CDs) have been used for sterilization, hardly any anionic CDs with antimicrobial activity have appeared. In the present work, we engineered a string of anionic CDs (especially CD31) as valid broad-spectrum bactericides to kill bacteria. Furthermore, CD31 conjugated with ɛ-polylysine (Plys) to construct injectable, and self-healing hydrogel (CD-Plys) that possess the advantages of remarkable broad spectrum antibacterial activity, excellent wound healing ability and satisfied biocompatibility. CD-Plys could dramatically accelerate wound healing with epithelization and enhanced angiogenesis. Taken together, this work provides a two-pronged strategy to explore CDs-based antimicrobial agents for disease therapy and tissue engineering.
Topics: Anti-Bacterial Agents; Bacteria; Carbon; Hydrogels; Polylysine; Wound Healing
PubMed: 35953858
DOI: 10.1186/s12951-022-01572-w -
Medical Science Monitor : International... Sep 2017BACKGROUND The antimicrobial mechanisms of ε-polylysine (EPL) against Pseudomonas aeruginosa and Aspergillus fumigatus biofilm were investigated. MATERIAL AND METHODS...
BACKGROUND The antimicrobial mechanisms of ε-polylysine (EPL) against Pseudomonas aeruginosa and Aspergillus fumigatus biofilm were investigated. MATERIAL AND METHODS We assessed the changes in electric conductivity of broth and total sugar concentration, as well as changes in phosphorous metabolism and protein expression, of the 2 organisms before and after treatment with EPL. RESULTS The experimental results showed that EPL has antimicrobial activity against Pseudomonas aeruginosa and Aspergillus fumigatus, but the activity was much stronger for the former. After treatment with EPL, the electric conductivity and total sugar concentration of microbial broth increased, suggesting that EPL damages the cell membrane structure, which increases permeability of the cell membrane and release of cell components. CONCLUSIONS The consumption of phosphorous decreased in the EPL-treated organisms, which seriously affected the synthesis of important cell components such as nucleic acid and phospholipid, as well as energy metabolism.
Topics: Anti-Bacterial Agents; Anti-Infective Agents; Aspergillus fumigatus; Biofilms; Microbial Sensitivity Tests; Polylysine; Pseudomonas aeruginosa
PubMed: 28863128
DOI: 10.12659/msm.903145 -
Cells Jun 2021In human sperm cryopreservation, test yolk buffer and human serum albumin have been used as permeating macromolecular-weight cryoprotectants. In clinical reproductive...
In human sperm cryopreservation, test yolk buffer and human serum albumin have been used as permeating macromolecular-weight cryoprotectants. In clinical reproductive medicine, human serum albumin is frequently used because of low risks of zoonoses and allergic reactions. However, the risk of allogeneic infectious diseases exists, and the supply may be unstable because human serum albumin is derived from human blood. Therefore, the development of xeno-free human sperm cryopreservative reagents that could overcome the aforementioned problems is warranted. We succeeded in developing a new xeno-free and defined sperm cryopreservation reagent containing glycerol, carboxylated poly-l-lysine, and raffinose. The cryopreservation reagent was not significantly different in terms of sperm motility, viability, and DNA fragmentation and was comparable in performance to a commercial cryopreservation reagent containing human serum albumin. Moreover, the addition of saccharides was essential for its long-term storage. These results may help elucidate the unknown function of macromolecular-weight permeating cryoprotective agents.
Topics: Cryopreservation; Cryoprotective Agents; Glycerol; Humans; Male; Polylysine; Raffinose; Specimen Handling; Spermatozoa
PubMed: 34201225
DOI: 10.3390/cells10061435 -
Molecules (Basel, Switzerland) Oct 2019ε-Polylysine (ε-PL) was studied for the growth inhibition of (). The minimal inhibitory concentration (MIC) of ε-PL against was measured by the broth dilution...
ε-Polylysine (ε-PL) was studied for the growth inhibition of (). The minimal inhibitory concentration (MIC) of ε-PL against was measured by the broth dilution method, while the membrane permeability and metabolism of were assessed after ε-PL treatment. Additionally, growth curves, the content of alkaline phosphatase (AKP), the electrical conductivity (EC), the UV absorbance and scanning electron microscope (SEM) data were used to study cellular morphology. The impact of ε-PL on cell metabolism was also investigated by different methods, such as enzyme activity (peroxidase [POD], catalase [CAT], succinodehydrogenase [SDH] and malic dehydrogenase [MDH]) and cell metabolic activity. The results showed that the MIC of ε-PL against was 1.0 mg/mL. When was treated with ε-PL, the growth of the bacteria was inhibited and the AKP content, electrical conductivity and UV absorbance were increased, which demonstrated that ε-PL could damage the cell structure. The enzyme activities of POD, CAT, SDH, and MDH in the bacterial solution with ε-PL were decreased compared to those in the ordinary bacterial solution. As the concentration of ε-PL was increased, the enzyme activity decreased further. The respiratory activity of was also inhibited by ε-PL. The results suggest that ε-PL acts on the cell membrane of , thereby increasing membrane permeability and inhibiting enzyme activity in relation to respiratory metabolism and cell metabolism. This leads to inhibition of cell growth, and eventually cell death.
Topics: Anti-Bacterial Agents; Cell Membrane; Energy Metabolism; Microbial Sensitivity Tests; Microbial Viability; Models, Molecular; Polylysine; Shewanella putrefaciens
PubMed: 31623152
DOI: 10.3390/molecules24203727 -
Scientific Reports Oct 2023The design of biomaterials able to facilitate cell adhesion is critical in the field of tissue engineering. Precise control of surface chemistry at the material/tissue...
The design of biomaterials able to facilitate cell adhesion is critical in the field of tissue engineering. Precise control of surface chemistry at the material/tissue interface plays a major role in enhancing the interactions between a biomaterial and living cells. Bio-integration is particularly important in case of various electrotherapies, since a close contact between tissue and electrode's surface facilitates treatment. A promising approach towards surface biofunctionalization involves the electrografting of diazonium salts followed by the modification of organic layer with pro-adhesive polypeptides. This study focuses on the modification of platinum electrodes with a 4-nitrobenzenediazonium layer, which is then converted to the aminobenzene moiety. The electrodes are further biofunctionalized with polypeptides (polylysine and polylysine/laminin) to enhance cell adhesion. This study also explores the differences between physical and chemical coupling of selected polypeptides to modulate pro-adhesive nature of Pt electrodes with respect to human neuroblastoma SH-SY5Y cells and U87 astrocytes. Our results demonstrate the significant enhancement in cell adhesion for biofunctionalized electrodes, with more amplified adhesion noted for covalently coupled polypeptides. The implications of this research are crucial for the development of more effective and functional biomaterials, particularly biomedical electrodes, which have the potential to advance the field of bioelectronics and improve patients' outcomes.
Topics: Humans; Polylysine; Adhesives; Neuroblastoma; Biocompatible Materials; Peptides; Cell Adhesion; Surface Properties
PubMed: 37884622
DOI: 10.1038/s41598-023-45694-z -
Journal of Proteome Research May 2018C-terminal polylysine (PL) can be synthesized from the polyadenine tail of prematurely cleaved mRNAs or when a read-though of a stop codon happens. Due to the highly...
C-terminal polylysine (PL) can be synthesized from the polyadenine tail of prematurely cleaved mRNAs or when a read-though of a stop codon happens. Due to the highly positive charge, PL stalls in the electrostatically negative ribosomal exit channel. The stalled polypeptide recruits the Ribosome-associated quality control (RQC) complex which processes and extracts the nascent chain. Dysfunction of the RQC leads to the accumulation of PL-tagged proteins, induction of a stress response, and cellular toxicity. Not much is known about the PL-specific aspect of protein quality control. Using quantitative mass spectrometry, we uncovered the post-ribosomal PL-processing machinery in human cytosol. It encompasses key cytosolic complexes of the proteostasis network, such as chaperonin TCP-1 ring complexes (TRiC) and half-capped 19S-20S proteasomes. Furthermore, we found that the nuclear transport machinery associates with PL, which suggests a novel mechanism by which faulty proteins can be compartmentalized in the cell. The enhanced nuclear import of a PL-tagged polypeptide confirmed this implication, which leads to questions regarding the biological rationale behind it.
Topics: Active Transport, Cell Nucleus; Chaperonin Containing TCP-1; Cytosol; HEK293 Cells; Humans; Mass Spectrometry; Polylysine; Proteasome Endopeptidase Complex; Proteolysis; Proteostasis; Ribosomes; Static Electricity
PubMed: 29634277
DOI: 10.1021/acs.jproteome.8b00108 -
Amino Acids Apr 2021α-Poly-L-lysine (PLL) has been used for various purposes such as cell attachment, immunization, and molecular delivery, and is known to be cytotoxic to several cell...
α-Poly-L-lysine (PLL) has been used for various purposes such as cell attachment, immunization, and molecular delivery, and is known to be cytotoxic to several cell lines. Here, we studied the effect of PLL on the adipogenesis of 3T3-L1 cells and investigated the underlying mechanism. Differentiation media containing PLL with a molecular weight (MW) greater than 4 kDa enhanced lipid droplet formation and increased adipogenic marker levels, indicating an increase in adipocyte differentiation. PLL with a molecular weight between 30 and 70 kDa was more effective than PLL of other sizes in 3T3-L1 cell differentiation. Moreover, PLL induced 3T3-L1 adipogenesis in insulin-free adipocyte differentiation medium. Incubation with insulin and PLL exhibited greater adipogenesis than insulin treatment only even at a high concentration. PLL stimulated insulin signaling and augmented the signaling pathway when it was added with insulin. While PLL did not activate the glucocorticoid receptor, which is phosphorylated by dexamethasone (DEX), it showed a positive effect on the cAMP signal pathway when preadipocytes were treated with PLL and 3-isobutyl-1-methylxanthine (IBMX). Consistent with these results, incubation with PLL and DEX without IBMX induced adipocyte differentiation. We also observed that the mitotic clonal expansion phase was the critical stage in adipogenesis for inducing the effects of PLL. These results suggest that PLL functions as an adipogenic inducer in 3T3-L1 preadipocytes and PLL has a direct effect on insulin signaling, one of the main regulatory pathways.
Topics: 1-Methyl-3-isobutylxanthine; 3T3-L1 Cells; Adipogenesis; Animals; Cell Differentiation; Cyclic AMP; Dexamethasone; Insulin; Mice; Molecular Weight; Polylysine; Signal Transduction
PubMed: 33743070
DOI: 10.1007/s00726-020-02932-2