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Biomaterials Science Oct 2023The active transport of nanoparticles into solid tumors through transcytosis has been recognized as a promising way to enhance tumor accumulation and penetration, but...
The active transport of nanoparticles into solid tumors through transcytosis has been recognized as a promising way to enhance tumor accumulation and penetration, but the effect of the physicochemical properties of nanoparticles remains unclear. Herein, we develop a type of single-molecule dual imaging nanodot by divergent growth of perylenediimide (PDI)-dye-cored polylysine dendrimers and internal orthogonal conjugation of Gd(III)-based macrocyclic probes for fluorescence imaging and magnetic resonance imaging (MRI) of surface chemistry-dependent tumor entrance. The MRI and fluorescence imaging show that sixth-generation nanodots with acetylated (G6-Ac) and oligo ethylene glycol (G6-OEG) surfaces exhibit similar high tumor accumulation but different intratumor distribution. Cellular uptake and transport experiments suggest that G6-Ac nanodots have lower lysosomal entrapment (61% 83%) and a higher exocytotic rate (47% 29%) than G6-OEG. Therefore, G6-Ac is more likely to undergo intercellular transport through cell transcytosis, and is able to reach a tumor area distant from blood vessels, while G6-OEG mainly enters the tumor through enhanced permeability and retention (EPR) effect-based passive transport, and is not able to deliver to distant tumor areas. This study suggests that it is possible to boost the tumor entrance of nanoparticles by engineering surface chemistry for active transport.
PubMed: 37665277
DOI: 10.1039/d3bm01171b -
Bioactive Materials Jul 2023Native-like endothelium regeneration is a prerequisite for material-guided small-diameter vascular regeneration. In this study, a novel strategy is proposed to achieve...
Native-like endothelium regeneration is a prerequisite for material-guided small-diameter vascular regeneration. In this study, a novel strategy is proposed to achieve phase-adjusted endothelial healing by step-wise modification of parallel-microgroove-patterned (i.e., micropatterned) nanofibers with polydopamine-copper ion (PDA-Cu) complexes, polylysine (PLys) molecules, and Cys-Ala-Gly (CAG) peptides (CAG@PLys@PDA-Cu). Using electrospun poly(-lactide--caprolactone) random nanofibers as the demonstrating biomaterial, step-wise modification of CAG@PLys@PDA-Cu significantly enhanced substrate wettability and protein adsorption, exhibited an excellent antithrombotic surface and outstanding phase-adjusted capacity of endothelium regeneration involving cell adhesion, endothelial monolayer formation, and the regenerated endothelium maturation. Upon implantation for segmental replacement of rabbit carotid arteries, CAG@PLys@PDA-Cu modified grafts (2 mm inner diameter) with micropatterns on inner surface effectively accelerated native-like endothelium regeneration within 1 week, with less platelet aggregates and inflammatory response compared to those on non-modified grafts. Prolonged observations at 6- and 12-weeks post-implantation demonstrated a positive vascular remodeling with almost fully covered endothelium and mature smooth muscle layer in the modified vascular grafts, accompanied with well-organized extracellular matrix. By contrast, non-modified vascular grafts induced a disorganized tissue formation with a high risk of thrombogenesis. In summary, step-wise modification of CAG@PLys@PDA-Cu on micropatterned nanofibers can significantly promote endothelial healing without inflicting thrombosis, thus confirming a novel strategy for developing functional vascular grafts or other blood-contacting materials/devices.
PubMed: 37056258
DOI: 10.1016/j.bioactmat.2022.07.010 -
International Journal of Biological... Dec 2023Cancer drugs usually have side effects in chemotherapy. Apoptin, a protein recognized by its good therapeutical effect on tumors and innocuous to body, is employed to...
Cancer drugs usually have side effects in chemotherapy. Apoptin, a protein recognized by its good therapeutical effect on tumors and innocuous to body, is employed to treat hepatocellular carcinoma (HCC). As our previous data shown, the efficiency of apoptin protein might be limited by the protein of apaf-1. Therefore, we designed the multi-functional nanoparticles (MFNPs) encapsulating apoptin and apaf-1 plasmids by layer-by layer assembly. The NPs could release drugs into tumor site specifically and had good compatibility to normal cells and tissues. The groups of biotin, ε-polylysine, and nuclear localization signal in MFNPs conferred NPs the capabilities to enter cancer cells specifically, escape lysosome and enter the nucleus, respectively. In vitro inhibition experiment and in vivo anti-tumor therapy confirmed MFNPs as an excellent carrier to treat HCC. In addition, the dual-drug system was superior to any of the single-drug system. The mechanism analysis proved that supplement of the protein of apaf-1 might enhance apoptosome formation, causing the increase of therapeutical efficacy.
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; Apoptotic Protease-Activating Factor 1; Capsid Proteins; Apoptosis; Plasmids; Nanoparticles
PubMed: 37703966
DOI: 10.1016/j.ijbiomac.2023.126870 -
Reproduction in Domestic Animals =... Jul 2023Carboxylated poly-l-lysine (CPLL) is an anti-freeze agent having pronounced non-permeating yet membrane stabilizing cryoprotective capabilities. The objective was to...
Carboxylated poly-l-lysine (CPLL) is an anti-freeze agent having pronounced non-permeating yet membrane stabilizing cryoprotective capabilities. The objective was to evaluate the CPLL supplementation in extender in terms of post-thaw quality (sperm), total anti-oxidant activity (milt) and fertilization potential of cryopreserved Labeo rohita sperm. For this purpose, male brood fish reared at a fish seed hatchery, Rawal Town Islamabad, Pakistan were captured from different rearing ponds and acclimatized in hatchery ponds for 6 h. The brooder was injected with Ovaprim (0.2 mL/kg), and milt was collected after 8 h in cooled sterilized falcon tubes, maintained at 4°C and evaluated for sperm motility. The milt collected from three brooders (n = 3) was diluted in extenders viz., modified Kurokura-2 extender having 10% methanol (control); experimental extenders with CPLL supplementation at the rate of 0.5%, 1% and 1.5%. Diluted milt was filled in 0.5 mL straws, exposed to liquid nitrogen vapours and cryopreserved. Cryopreserved milt was thawed at 25°C and assessed for post-thaw sperm quality. Sperm motility, motility duration, viability, total anti-oxidant capacity and DNA integrity was significantly higher (p < 0.05) in the extender having 1.5% CPLL than control. To evaluate the fertilization rates, male and female brooders were injected with Ovaprim at 0.2 mL/Kg and 0.5 mL/Kg body weight respectively. Fresh eggs and milt were collected through abdominal stripping. Batches of 10 g of eggs from each female (n = 2) were fertilized with one straw, each from frozen sperm with KE + methanol (control), KE + methanol + 1.5% CPLL and 50 μL fresh milt (negative control). After 1.5 h of fertilization, eggs were collected from all jars and a total of 200 eggs were counted. The fertilized eggs appeared clear and transparent while unfertilized eggs looked opaque with disintegrated nuclei. Sperm fertilization rate (%) was higher (p < 0.05) in extender KE + methanol + 1.5% CPLL (78.7 ± 0.5) compared to control (KE + methanol) (52.0 ± 0.4) however, it was lower compared to that of negative control, the fresh milt (85.2 ± 0.6). In conclusion, supplementation of carboxylated poly-l-lysine (1.5%) to modified Kurokura-2 extender having 10% methanol improves post-thaw motility, motility duration, viability, DNA integrity, anti-oxidant capacity (milt) and fertilizing ability of cryopreserved L. rohita sperm.
Topics: Male; Female; Animals; Polylysine; Sperm Motility; Methanol; Antioxidants; Semen Preservation; Cryoprotective Agents; Seeds; Spermatozoa; Cryopreservation
PubMed: 37191551
DOI: 10.1111/rda.14391 -
Food Chemistry Oct 2023PVA/CC/CUR/PL composite films containing curcumin (CUR) and ε-polylysine (PL) were prepared by casting and chemical grafting methods to address the threat to food...
PVA/CC/CUR/PL composite films containing curcumin (CUR) and ε-polylysine (PL) were prepared by casting and chemical grafting methods to address the threat to food spoilage. Morphological analysis showed that the grafting of CUR and PL resulted in a rough cross-section of the polymer matrix. Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD) analysis confirmed the grafting of CUR and PL into the polymer matrix via esterification and amidation reactions, respectively. Thermal weight loss analysis showed that grafting process positively improved the thermal stability. The PVA/CC/CUR/PL films exhibited strong bactericidal activity, reaching 99.0% and 99.8% for Pseudomonas lundensis and Shewanella putrefaciens, respectively. After 8 days of storage, the total number of colonies and the TVB-N content in the PVA/CC/CUR/PL group decreased by 1.51 lg CFU/g and 13.77 mg/100 g, respectively. Therefore, PVA/CC/CUR/PL films are considered as a promising bactericidal material with good mechanical properties, functionality, and other excellent characteristics.
Topics: Animals; Polylysine; Cellulose; Curcumin; Chickens; Hydrogels; Anti-Bacterial Agents
PubMed: 37224635
DOI: 10.1016/j.foodchem.2023.136345 -
Nature Communications May 2024In this randomized phase II clinical trial, we evaluated the effectiveness of adding the TLR agonists, poly-ICLC or resiquimod, to autologous tumor lysate-pulsed... (Randomized Controlled Trial)
Randomized Controlled Trial
In this randomized phase II clinical trial, we evaluated the effectiveness of adding the TLR agonists, poly-ICLC or resiquimod, to autologous tumor lysate-pulsed dendritic cell (ATL-DC) vaccination in patients with newly-diagnosed or recurrent WHO Grade III-IV malignant gliomas. The primary endpoints were to assess the most effective combination of vaccine and adjuvant in order to enhance the immune potency, along with safety. The combination of ATL-DC vaccination and TLR agonist was safe and found to enhance systemic immune responses, as indicated by increased interferon gene expression and changes in immune cell activation. Specifically, PD-1 expression increases on CD4+ T-cells, while CD38 and CD39 expression are reduced on CD8+ T cells, alongside an increase in monocytes. Poly-ICLC treatment amplifies the induction of interferon-induced genes in monocytes and T lymphocytes. Patients that exhibit higher interferon response gene expression demonstrate prolonged survival and delayed disease progression. These findings suggest that combining ATL-DC with poly-ICLC can induce a polarized interferon response in circulating monocytes and CD8+ T cells, which may represent an important blood biomarker for immunotherapy in this patient population.Trial Registration: ClinicalTrials.gov Identifier: NCT01204684.
Topics: Humans; Dendritic Cells; Glioma; Female; Male; Interferons; Middle Aged; Cancer Vaccines; CD8-Positive T-Lymphocytes; Poly I-C; Adult; Toll-Like Receptors; Imidazoles; Aged; Vaccination; Monocytes; Brain Neoplasms; CD4-Positive T-Lymphocytes; Immunotherapy; Toll-Like Receptor Agonists; Carboxymethylcellulose Sodium; Polylysine
PubMed: 38719809
DOI: 10.1038/s41467-024-48073-y -
Biomedical Materials (Bristol, England) Aug 2023An optimal wound-healing hydrogel requires effective antibacterial properties and a favorable cell adhesion and proliferation environment. Althoughsilk fibroin (SF)...
An optimal wound-healing hydrogel requires effective antibacterial properties and a favorable cell adhesion and proliferation environment. Althoughsilk fibroin (SF) possesses inherent wound-healing properties, it lacks these essential qualities. This study aimed to fabricate a novel photo-polymerizable hydrogel by utilizing SF's wound-healing efficiency and the epsilon-poly-L-lysine (EPL) antimicrobial activity. The SF was modified with three different concentrations of glycidyl methacrylate (GMA) to obtain SF-GMA(L), SF-GMA(M), and SF-GMA(H). A methacrylated EPL (EPL-GMA) was also produced. Then, SF-GMA was mixed with EPL-GMA to produce photo-crosslinkable SF-GMA-EPL hydrogels. The SF-GMA(L)-EPL, SF-GMA(M)-EPL, and SF-GMA(H)-EPL hydrogels, fabricated with 20% EPL-GMA, demonstrated maximum antimicrobial activity and mammalian cell adhesion ability. The hydroxyl radical (•OH) scavenging efficiency of the hydrogels was tested and shown to be between 69% and 74%. These hydrogels also exhibited 60% efficiency in removing bacterial lipopolysaccharides. The water absorption ability of the hydrogels was consistent with the size of their internal pores. The hydrogels exhibited a slow degradation fashion, and their degradation products appeared cytocompatible. Finally, the elastomeric properties of the hydrogels were determined, and a storage modulus (G') of 300-600 Pa was demonstrated. In conclusion, the hydrogels created in this study possess excellent biological and physical properties to support wound healing.
Topics: Animals; Fibroins; Polylysine; Hydrogels; Wound Healing; Anti-Infective Agents; Silk; Mammals
PubMed: 37567188
DOI: 10.1088/1748-605X/acef86 -
Journal of Materials Chemistry. B Oct 2023Uncontrollable bleeding is a crucial factor that can lead to fatality. Therefore, the development of hemostatic dressings that enable rapid hemostasis is of utmost...
Uncontrollable bleeding is a crucial factor that can lead to fatality. Therefore, the development of hemostatic dressings that enable rapid hemostasis is of utmost importance. Hydrogels with injectability, self-healing ability, and adhesiveness hold significant potential as effective hemostatic dressings. Herein, a composite hydrogel was fabricated by the oxidized Konjac glucomannan and ε-polylysine. After the encapsulation of a hemostatic drug, etamsylate, an oxidized Konjac glucomannan/ε-polylysine/etamsylate (OKGM/PL/E) composite hydrogel that possesses favorable properties including injectability, self-healing ability, tissue adhesiveness, hemocompatibility and cytocompatibility was fabricated. The OKGM/PL/E hydrogel demonstrated the ability to effectively adhere red blood cells and seal wounds, enabling rapid control of hemorrhaging. wound healing experiments confirmed the hemostatic and wound healing efficacy of the OKGM/PL/E hydrogel, highlighting its potential as a valuable hemostatic dressing.
Topics: Ethamsylate; Polylysine; Chitosan; Hydrogels; Wound Healing; Hemostasis; Hemostatics
PubMed: 37830374
DOI: 10.1039/d3tb01904g -
Food Chemistry: X Oct 2023For a long time, food spoilage posed a severe impairment on food safety and public health. Although chemical preservatives are commonly used to inhibit spoilage/...
For a long time, food spoilage posed a severe impairment on food safety and public health. Although chemical preservatives are commonly used to inhibit spoilage/ pathogenic microbial growth, the disadvantages of a single target, potential toxicity and high dose of use limit the better use of preservatives. In this research, the combination of natural preservatives: Natamycin (Nat), ε-polylysine (ε-PL), and Chitosan (CS) could achieve an excellent antimicrobial effect including bacteria and fungi, and reduce the usage of a single preservative. Compound preservatives could destroy microbial morphology and damage the integrity of the cell wall/membrane by leakage of protein and alkaline phosphatase (AKP). Besides, high-throughput sequencing revealed that compound preservatives could decrease microbial diversity and richness, especially, , , , and . Therefore, the combination of 1/8 × MIC CS, 1/4 × MIC ε-PL, and 1/2 × MIC Nat can achieve an excellent antibacterial effect, providing new ideas for food preservation.
PubMed: 37780335
DOI: 10.1016/j.fochx.2023.100872 -
Biomaterials Science Nov 2023The development of antibacterial dressings has attracted much attention to address the disordered wound healing caused by bacterial infection. Constructing dressings...
An antibacterial and healing-promoting collagen fibril constructed by the simultaneous strategy of fibril reconstitution and ε-polylysine anchoring for infected wound repair.
The development of antibacterial dressings has attracted much attention to address the disordered wound healing caused by bacterial infection. Constructing dressings that have desirable antibacterial activity and could promote wound healing is important for infected wound repair. Inspired by the role of the key regulator collagen fibrils with D-periodic functional domains in the physiological wound healing process, we developed an antibacterial and wound healing-promoting collagen fibril with a structure highly similar to natural collagen in ECM and inherent antibacterial activity by the simultaneous strategy of fibril reconstitution and the antibacterial agent ε-polylysine (ε-PL) anchoring. Accompanied by the fibrillogenesis of collagen molecules, the anchorage of ε-PL into collagen fibrils was actualized through the formation of the covalent bond catalyzed by transglutaminase (TGase) between ε-PL and collagen. The collagen fibril possessed natural D-periodicity and achieved 20% ε-PL graft yield by co-assembling collagen/ε-PL mediated by 25 U g TGase, which showed a satisfactory proliferation of L929 fibroblasts and sustained inhibition rates above 90% against and . The rat -infected dermal wound model further demonstrated that the reconstituted antibacterial collagen fibril visibly promoted re-epithelialization, new collagen deposition, and angiogenesis by down-regulating the inflammatory-relative gene IL-6 and up-regulating the relative activity factor expression of CD31, achieving accelerated infected wound healing with 61.89% ± 3.96% wound closure on postoperative day 7 and full closure on day 14.
Topics: Rats; Animals; Polylysine; Escherichia coli; Staphylococcus aureus; Collagen; Anti-Bacterial Agents; Hydrogels
PubMed: 37800173
DOI: 10.1039/d3bm01181j