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Pharmaceutics May 2024Dendrimers are potent nanocarriers in drug delivery systems because their structure can be precisely controlled. We previously reported that polyamidoamine (PAMAM)...
Dendrimers are potent nanocarriers in drug delivery systems because their structure can be precisely controlled. We previously reported that polyamidoamine (PAMAM) dendrimers that were modified with 1,2-cyclohexanedicarboxylic acid (CHex) and phenylalanine (Phe), PAMAM-CHex-Phe, exhibited an effective association with various immune cells, including T-cells. In this study, we synthesized various carboxy-terminal Phe-modified dendrimers with different linkers using phthalic acid and linear dicarboxylic acids to determine the association of these dendrimers with Jurkat cells, a T-cell model. PAMAM--hexyl-Phe demonstrated the highest association with Jurkat T-cells. In addition, dendri-graft polylysine (DGL) with CHex and Phe, DGL-CHex-Phe, was synthesized, and its association with Jurkat cells was investigated. The association of DGL-CHex-Phe with T-cells was higher than that of PAMAM-CHex-Phe. However, it was insoluble in water and thus it is unsuitable as a drug carrier. Model drugs, such as protoporphyrin IX and paclitaxel, were loaded onto these dendrimers, and the most model drug molecules could be loaded into PAMAM-CHex-Phe. PTX-loaded PAMAM-CHex-Phe exhibited cytotoxicity against Jurkat cells at a similar level to free PTX. These results suggest that PAMAM-CHex-Phe exhibited both efficient T-cell association and drug loading properties.
PubMed: 38931839
DOI: 10.3390/pharmaceutics16060715 -
International Journal of Nanomedicine 2024Persistent endodontic infections (PEIs) mediated by bacterial biofilm mainly cause persistent periapical inflammation, resulting in recurrent periapical abscesses and...
INTRODUCTION
Persistent endodontic infections (PEIs) mediated by bacterial biofilm mainly cause persistent periapical inflammation, resulting in recurrent periapical abscesses and progressive bone destruction. However, conventional root canal disinfectants are highly damaging to the tooth and periodontal tissue and ineffective in treating persistent root canal infections. Antimicrobial materials that are biocompatible with apical tissues and can eliminate PEIs-associated bacteria are urgently needed.
METHODS
Here, ε-poly (L-lysine) derived carbon quantum dots (PL-CQDs) are fabricated using pyrolysis to remove PEIs-associated bacterial biofilms.
RESULTS
Due to their ultra-small size, high positive charge, and active reactive oxygen species (ROS) generation capacity, PL-CQDs exhibit highly effective antibacterial activity against (), which is greatly dependent on PL-CQDs concentrations. 100 µg/mL PL-CQDs could kill in 5 min. Importantly, PL-CQDs effectively achieved a reduction of biofilms in the isolated teeth model, disrupting the dense structure of biofilms. PL-CQDs have acceptable cytocompatibility and hemocompatibility in vitro and good biosafety in vivo.
DISCUSSION
Thus, PL-CQDs provide a new strategy for treating -associated PEIs.
Topics: Enterococcus faecalis; Quantum Dots; Biofilms; Polylysine; Carbon; Animals; Gram-Positive Bacterial Infections; Anti-Bacterial Agents; Humans; Reactive Oxygen Species; Mice
PubMed: 38895145
DOI: 10.2147/IJN.S453385 -
Journal of Nanobiotechnology Jun 2024Osteoarthritis (OA) is a common degenerative joint disease which currently lacks of effective agents. It is therefore urgent and necessary to seek an effective approach...
Cartilage progenitor cells derived extracellular vesicles-based cell-free strategy for osteoarthritis treatment by efficient inflammation inhibition and extracellular matrix homeostasis restoration.
Osteoarthritis (OA) is a common degenerative joint disease which currently lacks of effective agents. It is therefore urgent and necessary to seek an effective approach that can inhibit inflammation and promote cartilage matrix homeostasis. Cartilage progenitor cells (CPCs) are identified as a cell population of superficial zone in articular cartilage which possess strong migration ability, proliferative capacity, and chondrogenic potential. Recently, the application of CPCs may represent a novel cell therapy strategy for OA treatment. There is growing evidence that extracellular vesicles (EVs) are primary mediators of the benefits of stem cell-based therapy. In this study, we explored the protective effects of CPCs-derived EVs (CPCs-EVs) on IL-1β-induced chondrocytes. We found CPCs-EVs exhibited chondro-protective effects in vitro. Furthermore, our study demonstrated that CPCs-EVs promoted matrix anabolism and inhibited inflammatory response at least partially via blocking STAT3 activation. In addition, liquid chromatography-tandem mass spectrometry analysis identified 991 proteins encapsulated in CPCs-EVs. By bioinformatics analysis, we showed that STAT3 regulatory proteins were enriched in CPCs-EVs and could be transported to chondrocytes. To promoting the protective function of CPCs-EVs in vivo, CPCs-EVs were modified with cationic peptide ε-polylysine-polyethylene-distearyl phosphatidylethanolamine (PPD) for surface charge reverse. In posttraumatic OA mice, our results showed PPD modified CPCs-EVs (PPD-EVs) effectively inhibited extracellular matrix catabolism and attenuated cartilage degeneration. Moreover, PPD-EVs down-regulated inflammatory factors expressions and reduced OA-related pain in OA mice. In ex-vivo cultured OA cartilage explants, PPD-EVs successfully promoted matrix anabolism and inhibited inflammation. Collectively, CPCs-EVs-based cell-free therapy is a promising strategy for OA treatment.
Topics: Extracellular Vesicles; Animals; Osteoarthritis; Extracellular Matrix; Mice; Chondrocytes; Inflammation; Cartilage, Articular; Stem Cells; Homeostasis; Mice, Inbred C57BL; Male; STAT3 Transcription Factor; Cells, Cultured; Interleukin-1beta
PubMed: 38890638
DOI: 10.1186/s12951-024-02632-z -
International Journal of Biological... Jun 2024Practical employment of silicon (Si) electrodes in lithium-ion batteries (LIBs) is limited due to the severe volume changes suffered during charging-discharging process,...
Practical employment of silicon (Si) electrodes in lithium-ion batteries (LIBs) is limited due to the severe volume changes suffered during charging-discharging process, causing serious capacity fading. Here, a composite polymer (CP-10) containing sodium carboxymethyl cellulose (CMC-Na) and poly-lysine (PL) is proposed for the binder of Si-based anodes, and a multifunctional strategy of "in-situ crosslinking" is achieved to alleviate the severe capacity degradation effectively. A cross-linked three-dimensional (3D) network is established through the strong hydrogen bonding interaction and reversible electrostatic interactions within CP-10, offering favorable mechanical tolerance for the extreme volume expansion of Si. Moreover, hydrogen bonding interaction along with ion-dipole interaction formed between CP-10 and Si surface enhance the bonding capability of Si-based anodes, promoting the maintenance of anodes' integrity. Consequently, over 800 cycles are achieved for the Si@CP-10 at 0.5C while maintaining a fixed discharge specific capacity of 1000 mAh g. Moreover, the Si/C@CP-10 can stably operate over 500 cycles with a capacity retention of 77.12 % at 1C. The prolonged cycling lifetime of Si/C and Si anodes suggests great potential for this strategy in promoting the implementation of high-capacity LIBs.
PubMed: 38880451
DOI: 10.1016/j.ijbiomac.2024.133050 -
Pesticide Biochemistry and Physiology Jun 2024ε-Poly-l-lysine (ε-PL) is an effective antimicrobial peptide for controlling fungal plant diseases, exhibiting significant antifungal activity and safety. Despite its...
ε-Poly-l-lysine (ε-PL) is an effective antimicrobial peptide for controlling fungal plant diseases, exhibiting significant antifungal activity and safety. Despite its known efficacy, the potential of ε-PL in combating plant bacterial diseases remains underexplored. This study evaluated the effectiveness of ε-PL and its nanomaterial derivative in managing tomato bacterial spot disease caused by Pseudomonas syringae pv. tomato. Results indicated that ε-PL substantially inhibited the growth of Pseudomonas syringae pv. tomato. Additionally, when ε-PL was loaded onto attapulgite (encoded as ATT@PL), its antibacterial effect was significantly enhanced. Notably, the antibacterial efficiency of ATT@PL containing 18.80 μg/mL ε-PL was even close to that of 100 μg/mL pure ε-PL. Further molecular study results showed that, ATT@PL stimulated the antioxidant system and the salicylic acid signaling pathway in tomatoes, bolstering the plants disease resistance. Importantly, the nanocomposite demonstrated no negative effects on both seed germination and plant growth, indicating its safety and aligning with sustainable agricultural practices. This study not only confirmed the effectiveness of ε-PL in controlling tomato bacterial spot disease, but also introduced an innovative high antibacterial efficiency ε-PL composite with good bio-safety. This strategy we believe can also be used in improving other bio-pesticides, and has high applicability in agriculture practice.
Topics: Pseudomonas syringae; Solanum lycopersicum; Polylysine; Anti-Bacterial Agents; Plant Diseases; Silicon Compounds; Magnesium Compounds
PubMed: 38879341
DOI: 10.1016/j.pestbp.2024.105959 -
Advanced Materials (Deerfield Beach,... Jun 2024Uncontrolled bleeding and wound infections following severe trauma pose significant challenges for existing tissue adhesives, primarily due to their weak wet adhesion,...
Uncontrolled bleeding and wound infections following severe trauma pose significant challenges for existing tissue adhesives, primarily due to their weak wet adhesion, slow adhesion formation, cytotoxicity concerns, and lack of antibacterial properties. Herein, an injectable hydrogel (denoted as ES gel) with rapid, robust adhesive sealing and inherent antibacterial activity based on ε-polylysine and a poly(ethylene glycol) derivative is developed. The engineered hydrogel exhibits rapid gelation behavior, high mechanical strength, strong adhesion to various tissues, and can sustain an ultrahigh burst pressure of 450 mmHg. It also presents excellent biocompatibility, biodegradability, antibacterial properties, and on-demand removability. Significantly improved hemostatic efficacy of ES gel compared to fibrin glue is demonstrated using various injury models in rats and rabbits. Remarkably, the adhesive hydrogel can effectively halt lethal non-compressible hemorrhages in visceral organs (liver, spleen, and heart) and femoral artery injury models in fully anticoagulated pigs. Furthermore, the hydrogel outperforms commercial products in sutureless wound closure and repair in the rat liver defect, skin incision, and infected full-thickness skin wound models. Overall, this study highlights the promising clinical applications of ES gel for managing uncontrolled hemorrhage, sutureless wound closure, and infected wound repair. This article is protected by copyright. All rights reserved.
PubMed: 38875445
DOI: 10.1002/adma.202404811 -
ACS Applied Materials & Interfaces Jun 2024Poly-l-lysine (PLL) and Matrigel, both classical coating materials for culture substrates in neural stem cell (NSC) research, present distinct interfaces whose effect on...
Poly-l-lysine (PLL) and Matrigel, both classical coating materials for culture substrates in neural stem cell (NSC) research, present distinct interfaces whose effect on NSC behavior at cellular and molecular levels remains ambiguous. Our investigation reveals intriguing disparities: although both PLL and Matrigel interfaces are hydrophilic and feature amine functional groups, Matrigel stands out with lower stiffness and higher roughness. Based on this diversity, Matrigel surpasses PLL, driving NSC adhesion, migration, and proliferation. Intriguingly, PLL promotes NSC differentiation into astrocytes, whereas Matrigel favors neural differentiation and the physiological maturation of neurons. At the molecular level, Matrigel showcases a wider upregulation of genes linked to NSC behavior. Specifically, it enhances ECM-receptor interaction, activates the YAP transcription factor, and heightens glycerophospholipid metabolism, steering NSC proliferation and neural differentiation. Conversely, PLL upregulates genes associated with glial cell differentiation and amino acid metabolism and elevates various amino acid levels, potentially linked to its support for astrocyte differentiation. These distinct transcriptional and metabolic activities jointly shape the divergent NSC behavior on these substrates. This study significantly advances our understanding of substrate regulation on NSC behavior, offering novel insights into optimizing and targeting the application of these surface coating materials in NSC research.
Topics: Polylysine; Neural Stem Cells; Laminin; Drug Combinations; Collagen; Cell Differentiation; Cell Proliferation; Proteoglycans; Animals; Cell Adhesion; Cell Movement; Mice
PubMed: 38874539
DOI: 10.1021/acsami.4c02575 -
International Journal of Nanomedicine 2024The emergence and rapid spread of multidrug-resistant bacteria (MRB) caused by the excessive use of antibiotics and the development of biofilms have been a growing...
INTRODUCTION
The emergence and rapid spread of multidrug-resistant bacteria (MRB) caused by the excessive use of antibiotics and the development of biofilms have been a growing threat to global public health. Nanoparticles as substitutes for antibiotics were proven to possess substantial abilities for tackling MRB infections via new antimicrobial mechanisms. Particularly, carbon dots (CDs) with unique (bio)physicochemical characteristics have been receiving considerable attention in combating MRB by damaging the bacterial wall, binding to DNA or enzymes, inducing hyperthermia locally, or forming reactive oxygen species.
METHODS
Herein, how the physicochemical features of various CDs affect their antimicrobial capacity is investigated with the assistance of machine learning (ML) tools.
RESULTS
The synthetic conditions and intrinsic properties of CDs from 121 samples are initially gathered to form the raw dataset, with Minimum inhibitory concentration (MIC) being the output. Four classification algorithms (KNN, SVM, RF, and XGBoost) are trained and validated with the input data. It is found that the ensemble learning methods turn out to be the best on our data. Also, ε-poly(L-lysine) CDs (PL-CDs) were developed to validate the practical application ability of the well-trained ML models in a laboratory with two ensemble models managing the prediction.
DISCUSSION
Thus, our results demonstrate that ML-based high-throughput theoretical calculation could be used to predict and decode the relationship between CD properties and the anti-bacterial effect, accelerating the development of high-performance nanoparticles and potential clinical translation.
Topics: Anti-Bacterial Agents; Machine Learning; Carbon; Microbial Sensitivity Tests; Quantum Dots; Humans; Polylysine; Algorithms
PubMed: 38855729
DOI: 10.2147/IJN.S451680 -
Journal of Colloid and Interface Science Jun 2024To overcome the biological barriers in the journey of systemic gene delivery, a multifaceted genomic synthetic nanomedicine was elaborated and strategically equipped...
To overcome the biological barriers in the journey of systemic gene delivery, a multifaceted genomic synthetic nanomedicine was elaborated and strategically equipped with a multiple of intriguing responsiveness. Particularly, core-shell plasmid DNA condensates were created based on polyionic complexation with block copolymer of polyethylene glycol (PEG)-polylysine (PLys), namely, the nanoscaled PLys&pDNA nanoparticle tethered with the biocompatible PEG surroundings. Furthermore, redox-reversible disulfide crosslinking was introduced into PLys&pDNA nanoparticle to accomplish adequate structural stabilities, and thermal-responsive polypropylacrylamide (PNIPAM) was introduced as the secondary intermediate surroundings onto the pre-formulated PLys&pDNA nanoparticle with the aim of preventing the potential enzymatic degradation from the environmental nucleases. Hence, hundreds of times prolonged survival and retention was determined in pertinent to the blood circulation properties. Additionally, the installation of a guide ligand at the distal end of PEG segments was proposed to encourage selective tumor uptake. A linear peptide of GPLGVRG, which is selectively susceptible to digestion by the tumor-enriched matrix metalloproteinase 2 (MMP-2), was used as the linkage between the shell and core. This peptide has been shown to detach the bio-inert PEGylation, resulting in further facilitated cell endocytosis and intracellular trafficking activities. Hence, the precisely defined synthetic nanomedicine, which exhibits desirable characteristics, efficient expression of the therapeutic gene in the affected cells, and contributed to potent therapeutic efficacy in systemic treatment of intractable tumors by encapsulating the anti-angiogenic gene.
PubMed: 38850862
DOI: 10.1016/j.jcis.2024.06.010 -
Acta Pharmaceutica Sinica. B Jun 2024Circular RNAs (circRNAs) are ideal biomarkers of oral squamous cell carcinoma (OSCC) because of their highly stable closed-loop structure, and they can act as microRNA...
Circular RNAs (circRNAs) are ideal biomarkers of oral squamous cell carcinoma (OSCC) because of their highly stable closed-loop structure, and they can act as microRNA (miRNA) sponges to regulate OSCC progression. By analyzing clinical samples, we identified circCPNE1, a dysregulated circRNA in OSCC, and its expression level was negatively correlated with the clinical stage of OSCC patients. Gain-of-function assays revealed the tumor-suppressive effect of circCPNE1, which was then identified as a miR-330-3p sponge. MiR-330-3p was recognized as a tumor promoter in multiple studies, consistent with our finding that it could promote the proliferation, migration, and invasion of OSCC cells. These results indicated that selective inhibition of miR-330-3p could be an effective strategy to inhibit OSCC progression. Therefore, we designed cationic polylysine-cisplatin prodrugs to deliver antagomiR-330-3p (a miRNA inhibitory analog) electrostatic interactions to form PP@miR nanoparticles (NPs). Paratumoral administration results revealed that PP@miR NPs effectively inhibited subcutaneous tumor progression and achieved partial tumor elimination (2/5), which confirmed the critical role of miR-330-3p in OSCC development. These findings provide a new perspective for the development of OSCC treatments.
PubMed: 38828155
DOI: 10.1016/j.apsb.2024.02.009