Novel multifunctional biomimetic injectable hybrid systems were synthesized. The physicochemical as well as biological in vitro and in vivo tests demonstrated that they are promising candidates for bone tissue regeneration. The hybrids are composed of a biopolymeric collagen/chitosan/hyaluronic acid matrix and amine group-functionalized silica particles decorated with apatite to which the alendronate molecules were coordinated. The components of these systems were integrated and stabilized by cross-linking with genipin, a compound of natural origin. They can be precisely injected into the diseased tissue in the form of a viscous sol or a partially cross-linked hydrogel, where they can serve as scaffolds for locally controlled bone tissue regeneration/remodeling by supporting the osteoblast formation/proliferation and maintaining the optimal osteoclast level. These materials lack systemic toxicity. They can be particularly useful for the repair of small osteoporotic bone defects.
Purpose The zoonotic opportunistic pathogen Staphylococcus pseudintermedius 222 produces BacSp222 – an atypical peptide exhibiting the features of a bacteriocin, a virulence factor, and a molecule modulating the host inflammatory reaction. The peptide is secreted in an unmodified form and, additionally, two forms modified posttranslationally by succinylation. This study is a comprehensive report focusing on the proinflammatory properties of such molecules. Methods The study was performed on mouse monocyte/macrophage-like and endothelial cell lines as well as human neutrophils. The following peptides were studied: BacSp222, its succinylated forms, the form deprived of formylated methionine, and a reference bacteriocin – nisin. The measurements of the nitric oxide (NO) level, induced NO synthase (iNOS) expression, the profile of secreted cytokines, NF-kappa-B activation, reactive oxygen species (ROS) biosynthesis, and the formation of extracellular traps were conducted to evaluate the proinflammatory activity of the studied peptides. Results BacSp222 and its succinylated forms effectively induced NO production and iNOS expression when combined with IFN-gamma in macrophage-like cells. All natural BacSp222 forms used alone or with IFN-gamma stimulated the production of TNF-alpha, MCP-1, and IL-1-alpha, while the co-stimulation with IFN-gamma increased IL-10 and IL-27. Upregulated TNF-alpha secretion observed after BacSp222 exposition resulted from increased expression but not from membrane TNF-alpha proteolysis. In neutrophils, all forms of bacteriocin upregulated IL-8, but did not induce ROS production or NETs formation. In all experiments, the activities of deformylated bacteriocin were lower or unequivocal in comparison to other forms of the peptide. Conclusion All naturally secreted forms of BacSp222 exhibit proinflammatory activity against monocyte-macrophage cells and neutrophils, confirming that the biological role of BacSp222 goes beyond bactericidal and cytotoxic effects. The atypical posttranslational modification (succinylation) does not diminish its immunomodulatory activity in contrast to the lower antibacterial potential or cytotoxicity of such modified form established in previous studies.
Cancer is one of the most important health problems of our population, and one of the common anticancer treatments is chemotherapy. The disadvantages of chemotherapy are related to the drug’s toxic effects, which act on cancer cells and the healthy part of the body. The solution of the problem is drug encapsulation and drug targeting. The present study aimed to develop a novel method of preparing multifunctional 5-Fluorouracil (5-FU) nanocarriers and their in vitro characterization. 5-FU polyaminoacid-based core@shell nanocarriers were formed by encapsulation drug-loaded nanocores with polyaminoacids multilayer shell via layer-by-layer method. The size of prepared nanocarriers ranged between 80–200 nm. Biocompatibility of our nanocarriers as well as activity of the encapsulated drug were confirmed by MTT tests. Moreover, the ability to the real-time observation of developed nanocarriers and drug accumulation inside the target was confirmed by fluorine magnetic resonance imaging (19F-MRI).
Control of nonspecific/specific protein adsorption is the main goal in the design of novel biomaterials, implants, drug delivery systems, and sensors. The specific functionalization of biomaterials can be achieved by proper surface modification. One of the important strategies is covering the materials with functional coatings. Therefore, our work aimed to functionalize multilayer coating to control nonspecific/specific protein adsorption. The polyelectrolyte coating was formed using a layer-by-layer technique (LbL) with biocompatible polyelectrolytes poly-L-lysine hydrobromide (PLL) and poly-L-glutamic acid (PGA). Nonspecific protein adsorption was minimized/eliminated by pegylation of multilayer films, which was achieved by adsorption of pegylated polycations (PLL-g-PEG). The influence of poly (ethylene glycol) chain length on eliminating nonspecific protein adsorption was confirmed. Moreover, to achieve specific protein adsorption, the multilayer film was also functionalized by immobilization of antibodies via a streptavidin bridge. The functional coatings were tested, and the adsorption of the following proteins confirmed the ability to control nonspecific/specific adsorption: human serum albumin (HSA), fibrinogen (FIB), fetal bovine serum (FBS), carcinoembryonic antigen human (CEA) monitored by quartz crystal microbalance with dissipation (QCM-D). AFM imaging of unmodified and modified multilayer surfaces was also performed. Functional multilayer films are believed to have the potential as a novel platform for biotechnological applications, such as biosensors and nanocarriers for drug delivery systems.
Introduction: Biodistribution of nanocarriers with a structure consisting of core and shell is most often analyzed using methods based on labeling subsequent compartments of nanocarriers. This approach may have serious limitations due to the instability of such complex systems under in vivo conditions. Methods: The core-shell polyelectrolyte nanocarriers were intravenously administered to healthy BALB/c mice with breast cancer. Next, biodistribution profiles and elimination routes were determined post mortem based on fluorescence measurements performed for isolated blood, tissue homogenates, collected urine, and feces. Results: Despite the surface PEGylation with PLL-g-PEG, multilayer polyelectrolyte nanocarriers undergo rapid degradation after intravenous administration. This process releases the shell components but not free Rhodamine B. Elements of polyelectrolyte shells are removed by hepatobiliary and renal clearance. Conclusion: Multilayer polyelectrolyte nanocarriers are prone to rapid degradation after intravenous administration. Fluorophore localization determines the obtained results of biodistribution and elimination routes of core-shell nanomaterials. Therefore, precise and reliable analysis of in vivo stability and biodistribution of nanomaterials composed of several compartments requires nanomaterials labeled within each compartment.
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