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ACS Biomaterials Science & Engineering May 2024Blood-contacting catheters play a pivotal role in contemporary medical treatments, particularly in the management of cardiovascular diseases. However, these catheters...
Blood-contacting catheters play a pivotal role in contemporary medical treatments, particularly in the management of cardiovascular diseases. However, these catheters exhibit inappropriate wettability and lack antimicrobial characteristics, which often lead to catheter-related infections and thrombosis. Therefore, there is an urgent need for blood contact catheters with antimicrobial and anticoagulant properties. In this study, we employed tannic acid (TA) and 3-aminopropyltriethoxysilane (APTES) to create a stable hydrophilic coating under mild conditions. Heparin (Hep) and poly(lysine) (PL) were then modified on the TA-APTES coating surface using the layer-by-layer (LBL) technique to create a superhydrophilic TA/APTES/(LBL) coating on silicone rubber (SR) catheters. Leveraging the superhydrophilic nature of this coating, it can be effectively applied to blood-contacting catheters to impart antibacterial, antiprotein adsorption, and anticoagulant properties. Due to Hep's anticoagulant attributes, the activated partial thromboplastin time and thrombin time tests conducted on SR/TA-APTES/(LBL) catheters revealed remarkable extensions of 276 and 103%, respectively, when compared to uncoated commercial SR catheters. Furthermore, the synergistic interaction between PL and TA serves to enhance the resistance of SR/TA-APTES/(LBL) catheters against bacterial adherence, reducing it by up to 99.9% compared to uncoated commercial SR catheters. Remarkably, the SR/TA-APTES/(LBL) catheter exhibits good biocompatibility with human umbilical vein endothelial cells in culture, positioning it as a promising solution to address the current challenges associated with blood-contact catheters.
Topics: Coated Materials, Biocompatible; Humans; Catheters; Polyphenols; Heparin; Tannins; Silanes; Anticoagulants; Propylamines; Amines; Anti-Bacterial Agents; Polylysine; Surface Properties; Hydrophobic and Hydrophilic Interactions; Human Umbilical Vein Endothelial Cells; Silicone Elastomers; Adsorption; Escherichia coli
PubMed: 38641433
DOI: 10.1021/acsbiomaterials.4c00578 -
International Journal of Biological... May 2024MicroRNAs (miRNAs) play important roles in plant defense against various pathogens. ε-poly-l-lysine (ε-PL), a natural anti-microbial peptide produced by...
MicroRNAs (miRNAs) play important roles in plant defense against various pathogens. ε-poly-l-lysine (ε-PL), a natural anti-microbial peptide produced by microorganisms, effectively suppresses tobacco mosaic virus (TMV) infection. To investigate the anti-viral mechanism of ε-PL, the expression profiles of miRNAs in TMV-infected Nicotiana tabacum after ε-PL treatment were analyzed. The results showed that the expression levels of 328 miRNAs were significantly altered by ε-PL. Degradome sequencing was used to identify their target genes. Integrative analysis of miRNAs target genes and gene-enriched GO/KEGG pathways indicated that ε-PL regulates the expression of miRNAs involved in critical pathways of plant hormone signal transduction, host defense response, and plant pathogen interaction. Subsequently, virus induced gene silencing combined with the short tandem targets mimic technology was used to analyze the function of these miRNAs and their target genes. The results indicated that silencing miR319 and miR164 reduced TMV accumulation in N. benthamiana, indicating the essential roles of these miRNAs and their target genes during ε-PL-mediated anti-viral responses. Collectively, this study reveals that microbial source metabolites can inhibit plant viruses by regulating crucial host miRNAs and further elucidate anti-viral mechanisms of ε-PL.
Topics: Nicotiana; Tobacco Mosaic Virus; MicroRNAs; Polylysine; Gene Expression Regulation, Plant; Transcriptome; Plant Diseases; Antiviral Agents; Gene Expression Profiling
PubMed: 38631577
DOI: 10.1016/j.ijbiomac.2024.131628 -
ACS Applied Materials & Interfaces Apr 2024Recently, paclitaxel (PTX) was reported to increase intracellular lipid reactive oxygen species (ROS) levels, triggering cancer cell ferroptosis. Based on this, some...
Recently, paclitaxel (PTX) was reported to increase intracellular lipid reactive oxygen species (ROS) levels, triggering cancer cell ferroptosis. Based on this, some efforts had been made to improve PTX treatment for non-small-cell lung cancer (NSCLC). Our previous studies demonstrated that triptolide (TPL) could improve the antitumor effect of PTX. Nevertheless, the poor solubility and side effects often limit the application of chemotherapy drugs. In this paper, we constructed a novel nanodrug delivery system (NDDS) chemosynthesis by PEGylated generation 3 (G3) dendritic polylysine coloaded with PTX and TPL (PTX-TPL-PEG-PLL, PTPP), which was endowed with the ability of tumor targeting and favorable solubility. In addition, we demonstrated that TPL could induce ROS generation by regulating the NF-κB signaling pathway to enhance the ferroptosis-induced effect of PTX. Besides, ferroptosis induced by PTPP could improve chemoresistance through inhibiting the level of P-gp, GPX4, and SLC7A11. Furthermore, we determined that ferroptosis may strengthen the immune response by increasing the expression of CD8 T cells and IFN-γ cells while decreasing Treg cells. In general, PTPP may be a potential system for NSCLC treatment.
PubMed: 38597227
DOI: 10.1021/acsami.4c00558 -
International Journal of Biological... May 2024Diabetic wounds are a significant clinical challenge. Developing effective antibacterial dressings is crucial for preventing wound ulcers caused by bacterial infections....
Diabetic wounds are a significant clinical challenge. Developing effective antibacterial dressings is crucial for preventing wound ulcers caused by bacterial infections. In this study, a self-healing antibacterial hydrogel (polyvinyl alcohol (PVA)-polylysine-gum arabic, PLG hydrogels) with near-infrared photothermal response was prepared by linking PVA and a novel polysaccharide-amino acid compound (PG) through borate bonding combined with freeze-thaw cycling. Subsequently, the hydrogel was modified by incorporating inorganic nanoparticles (modified graphene oxide (GM)). The experimental results showed that the PLGM hydrogels (PLG@GM hydrogels, 3.0 wt%) could effectively kill bacteria and promote diabetic wound tissue healing under 808-nm near-infrared laser irradiation. Therefore, this hydrogel system provides a new idea for developing novel dressings for treating diabetic wounds.
Topics: Wound Healing; Polyvinyl Alcohol; Hydrogels; Animals; Polylysine; Gum Arabic; Anti-Bacterial Agents; Diabetes Mellitus, Experimental; Rats; Sterilization; Male; Mice; Graphite
PubMed: 38582460
DOI: 10.1016/j.ijbiomac.2024.131395 -
International Journal of Biological... May 2024The development of antibiotic-loaded microneedles has been hindered for years by limited excipient options, restricted drug-loading space, poor microneedle formability,...
The development of antibiotic-loaded microneedles has been hindered for years by limited excipient options, restricted drug-loading space, poor microneedle formability, and short-term drug retention. Therefore, this study proposes a dissolving microneedle fabricated from the host-defense peptide ε-poly-l-lysine (EPL) as an antibacterial adjuvant system for delivering antibiotics. EPL serves not only as a major matrix material for the microneedle tips, but also as a broad-spectrum antibacterial agent that facilitates the intracellular accumulation of the antibiotic doxycycline (DOX) by increasing bacterial cell membrane permeability. Furthermore, the formation of physically crosslinked networks of EPL affords microneedle tips with improved formability, good mechanical properties, and amorphous nanoparticles (approximately 7.2 nm) of encapsulated DOX. As a result, a high total loading content of both antimicrobials up to 2319.1 μg/patch is achieved for efficient transdermal drug delivery. In a Pseudomonas aeruginosa-induced deep cutaneous infection model, the EPL microneedles demonstrates potent and long-term effects by synergistically enhancing antibiotic activities and prolonging drug retention in infected lesions, resulting in remarkable therapeutic efficacy with 99.91 % (3.04 log) reduction in skin bacterial burden after a single administration. Overall, our study highlights the distinct advantages of EPL microneedles and their potential in clinical antibacterial practice when loaded with amorphous DOX nanoparticles.
Topics: Polylysine; Doxycycline; Nanoparticles; Anti-Bacterial Agents; Animals; Needles; Pseudomonas aeruginosa; Mice; Drug Delivery Systems; Administration, Cutaneous; Skin; Pseudomonas Infections
PubMed: 38580030
DOI: 10.1016/j.ijbiomac.2024.131383 -
Biomaterials Advances Jun 2024Combating antimicrobial resistance is one of the biggest health challenges because of the ineffectiveness of standard biocide treatments. This challenge could be...
Remarkable enhancement of cinnamaldehyde antimicrobial activity encapsulated in capped mesoporous nanoparticles: A new "nanokiller" approach in the era of antimicrobial resistance.
Combating antimicrobial resistance is one of the biggest health challenges because of the ineffectiveness of standard biocide treatments. This challenge could be approached using natural products, which have demonstrated powerful therapeutics against multidrug-resistant microbes. In the present work, a nanodevice consisting of mesoporous silica nanoparticles loaded with an essential oil component (cinnamaldehyde) and functionalized with the polypeptide ε-poly-l-lysine is developed and used as an antimicrobial agent. In the presence of the corresponding stimuli (i.e., exogenous proteolytic enzymes from bacteria or fungi), the polypeptide is hydrolyzed, and the cinnamaldehyde delivery is enhanced. The nanodevice's release mechanism and efficacy are evaluated in vitro against the pathogenic microorganisms Escherichia coli, Staphylococcus aureus, and Candida albicans. The results demonstrate that the new device increases the delivery of the cinnamaldehyde via a biocontrolled uncapping mechanism triggered by proteolytic enzymes. Moreover, the nanodevice notably improves the antimicrobial efficacy of cinnamaldehyde when compared to the free compound, ca. 52-fold for E. coli, ca. 60-fold for S. aureus, and ca. 7-fold for C. albicans. The enhancement of the antimicrobial activity of the essential oil component is attributed to the decrease of its volatility due to its encapsulation in the porous silica matrix and the increase of its local concentration when released due to the presence of microorganisms.
Topics: Acrolein; Nanoparticles; Escherichia coli; Candida albicans; Silicon Dioxide; Staphylococcus aureus; Anti-Infective Agents; Porosity; Microbial Sensitivity Tests; Polylysine
PubMed: 38579520
DOI: 10.1016/j.bioadv.2024.213840 -
International Journal of Biological... May 2024
PubMed: 38579410
DOI: 10.1016/j.ijbiomac.2024.131302 -
Journal of Controlled Release :... May 2024Wound healing involves distinct phases, including hemostasis, inflammation, proliferation, and remodeling, which is a complex and dynamic process. Conventional...
Wound healing involves distinct phases, including hemostasis, inflammation, proliferation, and remodeling, which is a complex and dynamic process. Conventional preparations often fail to meet multiple demands and provide prompt information about wound status. Here, a pH/ROS dual-responsive hydrogel (OHA-PP@Z-CA@EGF) was constructed based on oxidized hyaluronic acid (OHA), phenylboronic acid-grafted ε-polylysine (PP), chlorogenic acid (CA)-loaded ZIF-8 (Z-CA), and epidermal growth factor (EGF), which possesses intrinsic antibacterial, antioxidant, and angiogenic capacities. Due to the Schiff base and Phenylboronate ester bonds, the hydrogel exhibited excellent mechanical properties, strong adhesion, good biodegradability, high biocompatibility, stable rheological properties, and self-healing ability. Moreover, introducing Z-CA as an initiator and nanofiller led to the additional cross-linking of hydrogel through coordination bonds, which further improved the mechanical properties and antioxidant capabilities. Bleeding models of liver and tail amputations demonstrated rapid hemostatic properties of the hydrogel. Besides, the hydrogel regulated macrophage phenotypes via the NF-κB/JAK-STAT pathways, relieved oxidative stress, promoted cell migration and angiogenesis, and accelerated diabetic wound healing. The hydrogel also enabled real-time monitoring of the wound healing stages by colorimetric detection. This multifunctional hydrogel opens new avenues for the treatment and management of full-thickness diabetic wounds.
Topics: Wound Healing; Animals; Chlorogenic Acid; Hydrogels; Nanocomposites; RAW 264.7 Cells; Mice; Macrophages; Antioxidants; Male; Phenotype; Rats, Sprague-Dawley; Polylysine; Hyaluronic Acid
PubMed: 38575075
DOI: 10.1016/j.jconrel.2024.03.054 -
International Journal of Biological... May 2024The challenge of drug resistance in bacteria caused by the over use of biotics is increasing during the therapy process, which has attracted great attentions of the...
The challenge of drug resistance in bacteria caused by the over use of biotics is increasing during the therapy process, which has attracted great attentions of the clinicians and scientists around the world. Recently, photodynamic therapy (PDT) triggered by photosensitizer (PS) has become a promising treatment method because of its high efficacy, easy operation, and low side effect. Herein, the poly-l-lysine (PLL) modified metal-organic framework (MOF) nanoparticles, ZIF/PLL-CIP/CUR, were synthesized to allow both reactive oxygen species (ROS) responsive drug release and photodynamic effect for synergistic therapy against drug resistant bacterial infections. The PLL was modified on the shell of the zeolite imidazole framework (ZIF) by the ROS-responsive thioketal linker for controllable CIP release. CUR were encapsulated in ZIF as the photosensitizer for blue light mediated photodynamic effect to produce singlet oxygen (O) and superoxide anion radical (O) for efficient inhibition towards methicillin-resistant Staphylococcus aureus (MRSA). The charge conversion from negative charge (-4.6 mV) to positive charge (2.6 mV) was observed at pH 7.4 and pH 5.5, and 70.9 % CIP was found released at pH 5.5 in the presence of HO, which suggests the good biosafety at physiological pH and ROS-responsive drug release of the as-prepared nanoparticle in the bacterial microenvironment. The as-prepared nanoparticles could effectively kill MRSA and disrupt bacterial biofilm by combination of chemo- and photodynamic therapy. In mice model, the as-prepared nanoparticles exhibited excellent biosafety and synergistic effect with 98.81 % healing rate in treatment of MRSA infection, which is considered as a promising candidate in combating drug resistant bacterial infection.
Topics: Polylysine; Photochemotherapy; Metal-Organic Frameworks; Nanoparticles; Animals; Mice; Reactive Oxygen Species; Hydrogen-Ion Concentration; Photosensitizing Agents; Methicillin-Resistant Staphylococcus aureus; Anti-Bacterial Agents; Drug Liberation; Curcumin; Staphylococcal Infections
PubMed: 38570003
DOI: 10.1016/j.ijbiomac.2024.131330 -
Journal of Agricultural and Food... Apr 2024Traditional petroleum-based food-packaging materials have poor permeability, limited active packaging properties, and difficulty in biodegradation, limiting their...
Characterization and Antioxidant and Antibacterial Activities of Carboxymethylated Tamarind Seed Polysaccharide Composite Films Incorporated with ε-Polylysine and Their Application in Fresh-Cut Green Bell Pepper Preservation.
Traditional petroleum-based food-packaging materials have poor permeability, limited active packaging properties, and difficulty in biodegradation, limiting their application. We developed a carboxymethylated tamarind seed polysaccharide composite film incorporated with ε-polylysine (CTPε) for better application in fresh-cut agricultural products. The CTPε films exhibit excellent water vapor barrier properties, but the mechanical properties are slightly reduced. Fourier transform infrared spectroscopy and X-ray diffraction spectra indicate the formation of hydrogen bonds between ε-PL and CTP, leading to their internal reorganization and dense network structure. With the increase of ε-PL concentration, composite films showed notable inhibition of postharvest pathogenic fungi and bacteria, a significant enhancement of 2,2'- azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) radical-scavenging activity, and gradual improvement of wettability performance. Cytotoxicity experiments confirmed the favorable biocompatibility when ε-PL was added at 0.3% (CTPε). In fresh-cut bell pepper preservation experiments, the CTPε coating effectively delayed weight loss and malondialdehyde increase preserved the hardness, color, and nutrients of fresh-cut peppers and prolonged the shelf life of the fresh-cut peppers, as compared with the control group. Therefore, CTPε composite films are expected to be a valuable packaging material for extending the shelf life of freshly cut agricultural products.
Topics: Antioxidants; Polylysine; Capsicum; Tamarindus; Anti-Bacterial Agents; Food Packaging; Polysaccharides; Seeds; Chitosan
PubMed: 38566515
DOI: 10.1021/acs.jafc.4c00092