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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 -
International Journal of Biological... Jun 2024The mass proliferation of seed cells and imitation of meat structures remain challenging for cell-cultured meat production. With excellent biocompatibility, high water...
The mass proliferation of seed cells and imitation of meat structures remain challenging for cell-cultured meat production. With excellent biocompatibility, high water content and porosity, hydrogels are frequently-studied materials for anchorage-dependent cell scaffolds in biotechnology applications. Herein, a scaffold based on gelatin/alginate/ε-Poly-l-lysine (GAL) hydrogel is developed for skeletal muscle cells, which has a great prospect in cell-cultured meat production. In this work, the hydrogel GAL-4:1, composed of gelatin (5 %, w/v), alginate (5 %, w/v) and ε-Poly-l-lysine (molar ratio vs. alginate: 4:1) is selected as cell scaffold based on Young's modulus of 11.29 ± 1.94 kPa, satisfactory shear-thinning property and suitable porous organized structure. The commercially available C2C12 mouse skeletal myoblasts and porcine muscle stem cells (PMuSCs), are cultured in the 3D-printed scaffold. The cells show strong ability of attachment, proliferation and differentiation after induction, showing high biocompatibility. Furthermore, the cellular bioprinting is performed with GAL-4:1 hydrogel and freshly extracted PMuSCs. The extracted PMuSCs exhibit high viability and display early myogenesis (desmin) on the 3D scaffold, suggesting the great potential of GAL hydrogel as 3D cellular constructs scaffolds. Overall, we develop a novel GAL hydrogel as a 3D-printed bioactive platform for cultured meat research.
Topics: Animals; Alginates; Gelatin; Polylysine; Cell Differentiation; Tissue Scaffolds; Swine; Printing, Three-Dimensional; Cell Proliferation; Mice; Hydrogels; Stem Cells; Meat; Muscle Development; Tissue Engineering; Cell Line; Bioprinting; In Vitro Meat
PubMed: 38821790
DOI: 10.1016/j.ijbiomac.2024.131980 -
Water Research Aug 2024Widespread outbreaks of threatening infections caused by unknown pathogens and water transmission have spawned the development of adsorption methods for pathogen...
Widespread outbreaks of threatening infections caused by unknown pathogens and water transmission have spawned the development of adsorption methods for pathogen elimination. We proposed a biochar functionalization strategy involving ε-polylysine (PLL), a bio-macromolecular poly(amino acid)s with variable folding conformations, as a "pathogen gripper" on biochar. PLL was successfully bridged onto biochar via polydopamine (PDA) crosslinking. The extension of electropositive side chains within PLL enables the capture of both nanoscale viruses and micrometer-scale bacteria in water, achieving excellent removal performances. This functionalized biochar was tentatively incorporated into ultrafiltration (UF) system, to achieve effective and controllable adsorption and retention of pathogens, and to realize the transfer of pathogens from membrane surface/pore to biochar surface as well as flushing water. The biochar-amended UF systems presents complete retention (∼7 LRV) and hydraulic elution of pathogens into membrane flushing water. Improvements in removal of organics and anti-fouling capability were observed, indicating the broken trade-off in UF pathogen removal dependent on irreversible fouling. Chemical characterizations revealed adsorption mechanisms encompassing electrostatic/hydrophobic interactions, pore filling, electron transfer, chemical bonding and secondary structure transitions. Microscopic and mechanical analyses validated the mechanisms for rapid adsorption and pathogen lysis. Low-concentration alkaline solution for used biochar regeneration, facilitated the deprotonation and transformation of PLL side chain to folded structures (α-helix/β-sheet). Biochar regeneration process also promoted the effective detachment/inactivation of pathogens and protection of functional groups on biochar, corroborated by physicochemical inspection and molecular dynamics simulation. The foldability of poly(amino acid)s acting like dynamic arms, significantly contributed to pathogen capture/desorption/inactivation and biochar regeneration. This study also inspires future investigation for performances of UF systems amended by poly(amino acid)s-functionalized biochar under diverse pressure, temperature, reactive oxygen species of feeds and chemical cleaning solutions, with far-reaching implications for public health, environmental applications of biochar, and UF process improvement.
Topics: Polylysine; Charcoal; Ultrafiltration; Adsorption; Water Purification; Polymers; Indoles
PubMed: 38820729
DOI: 10.1016/j.watres.2024.121834 -
Bioengineering & Translational Medicine May 2024Joint diseases, such as osteoarthritis, often require delivery of drugs to chondrocytes residing within the cartilage. However, intra-articular delivery of drugs to...
Joint diseases, such as osteoarthritis, often require delivery of drugs to chondrocytes residing within the cartilage. However, intra-articular delivery of drugs to cartilage remains a challenge due to their rapid clearance within the joint. This problem is further exacerbated by the dense and negatively charged cartilage extracellular matrix (ECM). Cationic nanocarriers that form reversible electrostatic interactions with the anionic ECM can be an effective approach to overcome the electrostatic barrier presented by cartilage tissue. For an effective therapeutic outcome, the nanocarriers need to penetrate, accumulate, and be retained within the cartilage tissue. Nanocarriers that adhere quickly to cartilage tissue after intra-articular administration, transport through cartilage, and remain within its full thickness are crucial to the therapeutic outcome. To this end, we used ring-opening polymerization to synthesize branched poly(l-lysine) (BPL) cationic nanocarriers with varying numbers of poly(lysine) branches, surface charge, and functional groups, while maintaining similar hydrodynamic diameters. Our results show that the multivalent BPL molecules, including those that are highly branched (i.e., generation two), can readily adhere and transport through the full thickness of cartilage, healthy and degenerated, with prolonged intra-cartilage retention. Intra-articular injection of the BPL molecules in mouse knee joint explants and rat knee joints showed their localization and retention. In summary, this study describes an approach to design nanocarriers with varying charge and abundant functional groups while maintaining similar hydrodynamic diameters to aid the delivery of macromolecules to negatively charged tissues.
PubMed: 38818117
DOI: 10.1002/btm2.10612 -
Analytical Chemistry Jun 2024Ion mobility mass spectrometry (IM-MS) measures the mass, size, and shape of ions in the same experiment, and structural information is provided via collision...
Ion mobility mass spectrometry (IM-MS) measures the mass, size, and shape of ions in the same experiment, and structural information is provided via collision cross-section (CCS) values. The majority of commercially available IM-MS instrumentation relies on the use of CCS calibrants, and here, we present data from a family of poly(l-lysine) dendrimers and explore their suitability for this purpose. In order to test these compounds, we employed three different IM-MS platforms (Agilent 6560 IM-QToF, Waters Synapt G2, and a home-built variable temperature drift tube IM-MS) and used them to investigate six different generations of dendrimers in two buffer gases (helium and nitrogen). Each molecule gives a highly discrete CCS distribution suggestive of single conformers for each / value. The CCS values of this series of molecules (molecular weight: 330-16,214 Da) range from 182 to 2941 Å, which spans the CCS range that would be found by many synthetic molecules including supramolecular compounds and many biopolymers. The CCS values for each charge state were highly reproducible in day-to-day analysis on each instrument, although we found small variations in the absolute CCS values between instruments. The rigidity of each dendrimer was probed using collisionally activated and high-temperature IM-MS experiments, where no evidence for a significant CCS change ensued. Taken together, this data indicates that these polymers are candidates for CCS calibration and could also help to reconcile differences found in CCS measurements on different instrument geometries.
Topics: Dendrimers; Polylysine; Ion Mobility Spectrometry; Mass Spectrometry; Molecular Conformation
PubMed: 38812282
DOI: 10.1021/acs.analchem.4c00099 -
ACS Applied Materials & Interfaces Jun 2024Biomaterial properties have recently been shown to modulate extracellular vesicle (EV) secretion and cargo; however, the effects of substrate composition on EV...
Biomaterial properties have recently been shown to modulate extracellular vesicle (EV) secretion and cargo; however, the effects of substrate composition on EV production remain underexplored. This study investigates the impacts of surface coatings composed of collagen I (COLI), fibronectin (FN), and poly l-lysine (PLL) on EV secretion for applications in therapeutic EV production and to further understanding of how changes in the extracellular matrix microenvironment affect EVs. EV secretion from primary bone marrow-derived mesenchymal stromal cells (BMSCs), primary adipose-derived stem cells (ASCs), HEK293 cells, NIH3T3 cells, and RAW264.7 cells was characterized on the different coatings. Expression of EV biogenesis genes and cellular adhesion genes was also analyzed. COLI coatings significantly decreased EV secretion in RAW264.7 cells, with associated decreases in cell viability and changes in EV biogenesis-related and cell adhesion genes at day 4. FN coatings increased EV secretion in NIH3T3 cells, while PLL coatings increased EV secretion in ASCs. Surface coatings had significant effects on the capacity of EVs derived from RAW264.7 and NIH3T3 cells to impact in vitro macrophage proliferation. Overall, surface coatings had different cell-specific effects on EV secretion and in vitro functional capacity, thus highlighting the potential of substrate coatings to further the development of clinical EV production systems.
Topics: Mice; Animals; Humans; Extracellular Vesicles; NIH 3T3 Cells; RAW 264.7 Cells; Mesenchymal Stem Cells; Fibronectins; Surface Properties; Polylysine; Coated Materials, Biocompatible; HEK293 Cells; Cell Proliferation; Cell Adhesion; Cell Survival; Collagen Type I
PubMed: 38805212
DOI: 10.1021/acsami.4c03213 -
Colloids and Surfaces. B, Biointerfaces Aug 2024Dental Implants are expected to possess both excellent osteointegration and antibacterial activity because poor osseointegration and infection are two major causes of...
Dental Implants are expected to possess both excellent osteointegration and antibacterial activity because poor osseointegration and infection are two major causes of titanium implant failure. In this study, we constructed layer-by-layer self-assembly films consisting of anionic casein phosphopeptides-amorphous calcium phosphate (CPP-ACP) and cationic poly (L-lysine) (PLL) on sandblasted and acid etched (SLA) titanium surfaces and evaluated their osseointegration and antibacterial performance in vitro and in vivo. The surface properties were examined, including microstructure, elemental composition, wettability, and Ca ion release. The impact the surfaces had on the adhesion, proliferation and differentiation abilities of MC3T3-E1 cells were investigated, as well as the material's antibacterial performance after exposure to the oral microorganisms such as Porphyromonas gingivalis (P. g) and Actinobacillus actinomycetemcomitans (A. a). For the in vivo studies, SLA and Ti (PLL/CA-3.0) implants were inserted into the extraction socket immediately after extracting the rabbit mandibular anterior teeth with or without exposure to mixed bacteria solution (P. g & A. a). Three rabbits in each group were sacrificed to collect samples at 2, 4, and 6 weeks of post-implantation, respectively. Radiographic and histomorphometry examinations were performed to evaluate the implant osseointegration. The modified titanium surfaces were successfully prepared and appeared as a compact nano-structure with high hydrophilicity. In particular, the Ti (PLL/CA-3.0) surface was able to continuously release Ca ions. From the in vitro and in vivo studies, the modified titanium surfaces expressed enhanced osteogenic and antibacterial properties. Hence, the PLL/CPP-ACP multilayer coating on titanium surfaces was constructed via a layer-by-layer self-assembly technology, possibly improving the biofunctionalization of Ti-based dental implants.
Topics: Titanium; Osseointegration; Animals; Polylysine; Surface Properties; Anti-Bacterial Agents; Mice; Dental Implants; Rabbits; Porphyromonas gingivalis; Caseins; Cell Proliferation; Aggregatibacter actinomycetemcomitans; Microbial Sensitivity Tests; Cell Adhesion; Cell Differentiation; Calcium Phosphates
PubMed: 38781846
DOI: 10.1016/j.colsurfb.2024.113966 -
Biomedical Physics & Engineering Express Jun 2024Lentiviral transduction is widely used in research, has shown promise in clinical trials involving gene therapy and has been approved for CAR-T cell immunotherapy....
Lentiviral transduction is widely used in research, has shown promise in clinical trials involving gene therapy and has been approved for CAR-T cell immunotherapy. However, most modifications are doneand rely on systemic administration of large numbers of transduced cells for clinical applications. A novel approach utilizingbiomaterial-based gene delivery can reduce off-target side effects while enhancing effectiveness of the manipulation process. In this study, poly(ethylene glycol) diacrylate (PEGDA)-based scaffolds were developed to enablelentivirus-mediated transduction. Compared to other widely popular biomaterials, PEGDA stands out due to its robustness and cost-effectiveness. These scaffolds, prepared via cryogelation, are capable of flowing through surgical needles in bothandconditions, and promptly regain their original shape. Modification with poly(L-lysine) (PLL) enables lentivirus immobilization while interconnected macroporous structure allows cell infiltration into these matrices, thereby facilitating cell-virus interaction over a large surface area for efficient transduction. Notably, these preformed injectable scaffolds demonstrate hemocompatibility, cell viability and minimally inflammatory response as shown by ourandstudies involving histology and immunophenotyping of infiltrating cells. This study marks the first instance of using preformed injectable scaffolds for delivery of lentivectors, which offers a non-invasive and localized approach for delivery of factors enablinglentiviral transduction suitable for both tissue engineering and immunotherapeutic applications.
Topics: Polyethylene Glycols; Cryogels; Humans; Gene Transfer Techniques; Lentivirus; Animals; Cell Survival; Tissue Scaffolds; Transduction, Genetic; Mice; Biocompatible Materials; Genetic Therapy; Surface Properties; Injections; Polylysine
PubMed: 38772344
DOI: 10.1088/2057-1976/ad4e3a -
Biomacromolecules Jun 2024Peptide-based supramolecular hydrogels are an attractive class of soft materials for biomedical applications when biocompatibility is a key requirement as they exploit...
Peptide-based supramolecular hydrogels are an attractive class of soft materials for biomedical applications when biocompatibility is a key requirement as they exploit the physical self-assembly of short self-assembling peptides avoiding the need for chemical cross-linking. Based on the knowledge developed through our previous work, we designed two novel peptides, (FKFE) and (FEFK), that form transparent hydrogels at pH 7. We characterized the phase behavior of these peptides and showed the clear link that exists between the charge carried by the peptides and the physical state of the samples. We subsequently demonstrate the cytocompatibility of the hydrogel and its suitability for 3D cell culture using 3T3 fibroblasts and human mesenchymal stem cells. We then loaded the hydrogels with two polymers, poly-l-lysine and dextran. When polymer and peptide fibers carry opposite charges, the size of the elemental fibril formed decreases, while the overall level of fiber aggregation and fiber bundle formation increases. This overall network topology change, and increase in cross-link stability and density, leads to an overall increase in the hydrogel mechanical properties and stability, i.e., resistance to swelling when placed in excess media. Finally, we investigate the diffusion of the polymers out of the hydrogels and show how electrostatic interactions can be used to control the release of large molecules. The work clearly shows how polymers can be used to tailor the properties of peptide hydrogels through guided intermolecular interactions and demonstrates the potential of these new soft hydrogels for use in the biomedical field in particular for delivery or large molecular payloads and cells as well as scaffolds for 3D cell culture.
Topics: Hydrogels; Humans; Mice; Static Electricity; Animals; Peptides; Mesenchymal Stem Cells; Polylysine; Biocompatible Materials; Dextrans; 3T3 Cells
PubMed: 38771115
DOI: 10.1021/acs.biomac.4c00232 -
Food Research International (Ottawa,... Jul 2024In light of the commendable advantages inherent in natural polymers such as biocompatibility, biodegradability, and cost-effectiveness, researchers are actively engaged... (Review)
Review
In light of the commendable advantages inherent in natural polymers such as biocompatibility, biodegradability, and cost-effectiveness, researchers are actively engaged in the development of biopolymer-based biodegradable food packaging films (BFPF). However, a notable limitation is that most biopolymers lack intrinsic antimicrobial activity, thereby restricting their efficacy in food preservation. To address this challenge, various active substances with antibacterial properties have been explored as additives to BFPF. Among these, ε-polylysine has garnered significant attention in BFPF applications owing to its outstanding antibacterial properties. This study provides a brief overview of the synthesis method and chemical properties of ε-polylysine, and comprehensively examines its impact as an additive on the properties of BFPF derived from diverse biopolymers, including polysaccharides, proteins, aliphatic polyesters, etc. Furthermore, the practical applications of various BFPF functionalized with ε-polylysine in different food preservation scenarios are summarized. The findings underscore that ε-polylysine, functioning as an antibacterial agent, not only directly enhances the antimicrobial activity of BFPF but also serves as a cross-linking agent, interacting with biopolymer molecules to influence the physical and mechanical properties of BFPF, thereby enhancing their efficacy in food preservation.
Topics: Polylysine; Food Packaging; Biopolymers; Food Preservation; Anti-Bacterial Agents; Edible Films
PubMed: 38763652
DOI: 10.1016/j.foodres.2024.114390