RESUMO
Background: Inhibiting ROS overproduction is considered a very effective strategy for the treatment of peripheral nerve injuries, and Se has a remarkable antioxidant effect; however, since the difference between the effective concentration of Se and the toxic dose is not large, we synthesized a nanomaterial that can release Se slowly so that it can be used more effectively. Methods: Se@SiO2 NPs were synthesized using a mixture of Cu2-x Se nanocrystals, and the mechanism of action of Se@SiO2 NPs was initially explored by performing sequencing, immunofluorescence staining and Western blotting of cellular experiments. The mechanism of action of Se@SiO2 NPs was further determined by performing behavioral assays after animal experiments and by sampling the material for histological staining, immunofluorescence staining, and ELISA. The effects, mechanisms and biocompatibility of Se@SiO2 NPs for peripheral nerve regeneration were determined. Results: Porous Se@SiO2 was successfully synthesized, had good particle properties, and could release Se slowly. CCK-8 experiments revealed that the optimal experimental doses were 100 µM H2O2 and 200 µg/mL Se@SiO2, and RNA-seq revealed that porous Se@SiO2 was associated with cell proliferation, apoptosis, and the PI3K/AKT pathway. WB showed that porous Se@SiO2 could increase the expression of cell proliferation antigens (PCNA and S100) and antiapoptotic proteins (Bcl-2), decrease the expression of proapoptotic proteins (Bax), and increase the expression of antioxidative stress proteins (Nrf2, HO-1, and SOD2). EdU cell proliferation and ROS fluorescence assays showed that porous Se@SiO2 promoted cell proliferation and reduced ROS levels. The therapeutic effect of LY294002 (a PI3K/AKT pathway inhibitor) was decreased significantly and its effect was lost when it was added simultaneously with porous Se@SiO2. Animal experiments revealed that the regenerated nerve fiber density, myelin thickness, axon area, gastrocnemius muscle wet-to-weight ratio, myofiber area, sciatic nerve function index (SFI), CMAP, apoptotic cell ratio, and levels of antioxidative stress proteins and anti-inflammatory factors were increased following the administration of porous Se@SiO2. The levels of oxidative stress proteins and anti-inflammatory factors were significantly greater in the Se@SiO2 group than in the PNI group, and the effect of LY294002 was decreased significantly and was lost when it was added simultaneously with porous Se@SiO2. Conclusion: Se@SiO2 NPs are promising, economical and effective Se-releasing nanomaterials that can effectively reduce ROS production, inhibit apoptosis and promote cell proliferation after nerve injury via the PI3K/AKT pathway, ultimately accelerating nerve regeneration. These findings could be used to design new, promising drugs for the treatment of peripheral nerve injury.
Assuntos
Proliferação de Células , Regeneração Nervosa , Traumatismos dos Nervos Periféricos , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Selênio , Transdução de Sinais , Dióxido de Silício , Animais , Selênio/química , Selênio/farmacologia , Dióxido de Silício/química , Dióxido de Silício/farmacologia , Traumatismos dos Nervos Periféricos/tratamento farmacológico , Fosfatidilinositol 3-Quinases/metabolismo , Transdução de Sinais/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Regeneração Nervosa/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Ratos , Apoptose/efeitos dos fármacos , Antioxidantes/farmacologia , Antioxidantes/química , Nanopartículas/química , Masculino , Preparações de Ação Retardada/farmacologia , Preparações de Ação Retardada/química , Ratos Sprague-Dawley , Estresse Oxidativo/efeitos dos fármacos , Nervo Isquiático/efeitos dos fármacos , Nervo Isquiático/lesões , Células de Schwann/efeitos dos fármacos , Células de Schwann/metabolismoRESUMO
Lower back pain (LBP) is a common condition closely associated with intervertebral disc degeneration (IDD), causing a significant socioeconomic burden. Inflammatory activation in degenerated discs involves pro-inflammatory cytokines, dysregulated regulatory cytokines, and increased levels of nerve growth factor (NGF), leading to further intervertebral disc destruction and pain sensitization. Macrophage polarization is closely related to autophagy. Based on these pathological features, a structured biomimetic nanoparticle coated with TrkA-overexpressing macrophage membranes (TMNP@SR) with a rapamycin-loaded mesoporous silica core is developed. TMNP@SR acted like sponges to adsorbe inflammatory cytokines and NGF and delivers the autophagy regulator rapamycin (RAPA) into macrophages through homologous targeting effects of the outer engineered cell membrane. By regulating autophagy activation, TMNP@SR promoted the M1-to-M2 switch of macrophages to avoid continuous activation of inflammation within the degenerated disc, which prevented the apoptosis of nucleus pulposus cells. In addition, TMNP@SR relieved mechanical and thermal hyperalgesia, reduced calcitonin gene-related peptide (CGRP) and substance P (SP) expression in the dorsal root ganglion, and downregulated GFAP and c-FOS signaling in the spinal cord in the rat IDD model. In summary, TMNP@SR spontaneously inhibits the aggravation of disc inflammation to alleviate disc degeneration and reduce the ingress of sensory nerves, presenting a promising treatment strategy for LBP induced by disc degeneration.
Assuntos
Autofagia , Degeneração do Disco Intervertebral , Nanopartículas , Ratos Sprague-Dawley , Degeneração do Disco Intervertebral/tratamento farmacológico , Degeneração do Disco Intervertebral/metabolismo , Animais , Autofagia/efeitos dos fármacos , Nanopartículas/química , Ratos , Masculino , Camundongos , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Dor Lombar/tratamento farmacológico , Materiais Biomiméticos/química , Materiais Biomiméticos/farmacologia , Sirolimo/farmacologia , Dióxido de Silício/química , Dióxido de Silício/farmacologia , Núcleo Pulposo/metabolismo , Inflamação/tratamento farmacológico , Citocinas/metabolismo , Biomimética/métodos , Modelos Animais de Doenças , Fator de Crescimento Neural/metabolismo , Células RAW 264.7RESUMO
Purpose: In this study, wound dressings were designed using zinc-modified marine collagen porous scaffold as host for wild bilberry (WB) leaves extract immobilized in functionalized mesoporous silica nanoparticles (MSN). These new composites were developed as an alternative to conventional wound dressings. In addition to the antibacterial activity of classic antibiotics, a polyphenolic extract could act as an antioxidant and/or an anti-inflammatory agent as well. Methods: Wild bilberry leaves extract was prepared by ultrasound-assisted extraction in ethanol and its properties were evaluated by UV-Vis spectroscopy (radical scavenging activity, total amount of polyphenols, flavonoids, anthocyanins, and condensed tannins). The extract components were identified by HPLC, and the antidiabetic properties of the extract were evaluated via α-glucosidase inhibitory activity. Spherical MSN were modified with propionic acid or proline moieties by post-synthesis method and used as carriers for the WB leaves extract. The textural and structural features of functionalized MSN were assessed by nitrogen adsorption/desorption isotherms, small-angle XRD, SEM, TEM, and FTIR spectroscopy. The composite porous scaffolds were prepared by freeze drying of the zinc-modified collagen suspension containing WB extract loaded silica nanoparticles. Results: The properties of the new composites demonstrated enhanced properties in terms of thermal stability of the zinc-collagen scaffold, without altering the protein conformation, and stimulation of NCTC fibroblasts mobility. The results of the scratch assay showed contributions of both zinc ions from collagen and the polyphenolic extract incorporated in functionalized silica in the wound healing process. The extract encapsulated in functionalized MSN proved enhanced biological activities compared to the extract alone: better inhibition of P. aeruginosa and S. aureus strains, higher biocompatibility on HaCaT keratinocytes, and anti-inflammatory potential demonstrated by reduced IL-1ß and TNF-α levels. Conclusion: The experimental data shows that the novel composites can be used for the development of effective wound dressings.
Assuntos
Bandagens , Colágeno , Nanopartículas , Extratos Vegetais , Folhas de Planta , Dióxido de Silício , Cicatrização , Zinco , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Folhas de Planta/química , Dióxido de Silício/química , Dióxido de Silício/farmacologia , Colágeno/química , Colágeno/farmacologia , Zinco/química , Zinco/farmacologia , Nanopartículas/química , Cicatrização/efeitos dos fármacos , Antibacterianos/farmacologia , Antibacterianos/química , Humanos , Alicerces Teciduais/química , Animais , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química , Linhagem Celular , Porosidade , Fibroblastos/efeitos dos fármacos , Antioxidantes/farmacologia , Antioxidantes/químicaRESUMO
The current longevity of dental resins intraorally is limited by susceptibility to acidic attacks from bacterial metabolic byproducts and vulnerability to enzymatic or hydrolytic degradation. Here, we demonstrate synthesizing an ionic liquid-based antibiofilm silane effective against Streptococcus mutans, a major caries pathogen. Furthermore, we incorporate this silane into dental resins, creating antibiofilm- and degradation-resistant materials applicable across resin types. FTIR, UV-vis, and NMR spectroscopy confirmed the synthesis of the expected ionic liquid-based silane. The characterization of SiO2 after the silanization indicated the presence of the silane and how it interacted with the oxide. All groups achieved a degree of conversion similar to that found for commercial resin composites immediately and after two months of storage in water. The minimum of 2.5 wt % of silane led to lower softening in solvent than the control group (GCTRL) (p < 0.05). While the flexural strength indicated a lower value from 1 wt % of silane compared to GCTRL (p < 0.05), the ultimate tensile strength did not indicate differences among groups (p > 0.05). There was no difference within groups between the immediate and long-term tests of flexural strength (p > 0.05) or ultimate tensile strength (p > 0.05). The addition of at least 5 wt % of silane reduced the viability of S. mutans compared to GCTRL (p < 0.05). The fluorescence microscopy analysis suggested that the higher the silane concentration, the higher the amount of bacteria with membrane defects. There was no difference among groups in the cytotoxicity test (p > 0.05). Therefore, the developed dental resins displayed biocompatibility, proper degree of conversion, improved resistance against softening in solvent, and stability after 6 months of storage in water. This material could be further developed to produce polymeric antimicrobial layers for different surfaces, supporting various potential avenues in developing novel biomaterials with enhanced therapeutic characteristics using ionic liquid-based materials.
Assuntos
Líquidos Iônicos , Nanopartículas , Silanos , Dióxido de Silício , Streptococcus mutans , Silanos/química , Silanos/farmacologia , Streptococcus mutans/efeitos dos fármacos , Dióxido de Silício/química , Dióxido de Silício/farmacologia , Líquidos Iônicos/química , Líquidos Iônicos/farmacologia , Nanopartículas/química , Antibacterianos/farmacologia , Antibacterianos/química , Animais , Resinas Compostas/química , Resinas Compostas/farmacologia , Camundongos , Biofilmes/efeitos dos fármacos , Resistência à TraçãoRESUMO
Antimicrobial drug development faces challenges from bacterial resistance, biofilms, and excessive inflammation. Here, we design an intelligent nanoplatform utilizing mesoporous silica nanoparticles doped with copper ions for loading copper sulfide (DM/Cu2+-CuS). The mesoporous silica doped with tetrasulfide bonds responds to the biofilm microenvironment (BME), releasing Cu2+ions, CuS along with hydrogen sulfide (H2S) gas. The release of hydrogen sulfide within 72 h reached 793.5 µM, significantly higher than that observed with conventional small molecule donors. H2S induces macrophages polarization towards the M2 phenotype, reducing inflammation and synergistically accelerating endothelial cell proliferation and migration with Cu2+ions. In addition, H2S disrupts extracellular DNA within biofilms, synergistically photothermal enhanced peroxidase-like activity of CuS to effectively eradicate biofilms. Remarkably, DM-mediated consumption of endogenous glutathione enhances the anti-biofilm activity of H2S and improves oxygen species (ROS) destruction efficiency. The combination of photothermal therapy (PTT), chemodynamic therapy (CDT), and gas treatment achieves sterilization rates of 99.3 % and 99.6 % against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli), respectively, in vitro under 808 nm laser irradiation. Additionally, in vivo experiments demonstrate a significant biosafety and antibacterial potential. In summary, the H2S donor developed in this study exhibits enhanced biocompatibility and controlled release properties. By integrating BME-responsive gas therapy with antibacterial ions, PTT and CDT, a synergistic multimodal strategy is proposed to offer new therapeutic approaches for wound healing. STATEMENT OF SIGNIFICANCE: The advanced DMOS/Cu2+-CuS (DMCC) multimodal therapeutic nanoplatform has been developed for the treatment of drug-resistant bacterial wound infections and has exhibited enhanced therapeutic efficacy through the synergistic effects of photothermal therapy, chemodynamic therapy, Cu2+ions, and H2S. The DMCC exhibited exceptional biocompatibility and could release CuS, Cu2+, and H2S in response to elevated concentrations of glutathione within the biofilm microenvironment. H2S effectively disrupted the biofilm structure. Meanwhile, peroxidase activity of CuS combined with GSH-mediated reduction of Cu2+ to Cu+ generated abundant hydroxyl radicals under acidic conditions, leading to efficient eradication of pathogenic bacteria. Furthermore, both H2S and Cu2+ could modulate M2 macrophages polarization and regulate immune microenvironment dynamics. These strategies collectively provided a novel approach for developing antibacterial nanomedical platforms.
Assuntos
Antibacterianos , Biofilmes , Cobre , Staphylococcus aureus , Cicatrização , Biofilmes/efeitos dos fármacos , Antibacterianos/farmacologia , Antibacterianos/química , Cicatrização/efeitos dos fármacos , Animais , Camundongos , Staphylococcus aureus/efeitos dos fármacos , Cobre/química , Cobre/farmacologia , Nanopartículas/química , Escherichia coli/efeitos dos fármacos , Terapia Fototérmica , Humanos , Terapia Combinada , Sulfeto de Hidrogênio/farmacologia , Sulfeto de Hidrogênio/química , Dióxido de Silício/química , Dióxido de Silício/farmacologia , Microambiente Celular/efeitos dos fármacos , Células RAW 264.7 , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismoRESUMO
Nanomaterial-based synergistic antibacterial agents are considered as promising tools to combat infections caused by antibiotic-resistant bacteria. Herein, multifunctional mesoporous silica nanoparticle (MSN)-based nanocomposites were fabricated for synergistic photothermal/photodynamic/chemodynamic therapy against methicillin-resistant Staphylococcus aureus (MRSA). MSN loaded with indocyanine green (ICG) as a core, while Prussian blue (PB) nanostructure was decorated on MSN surface via in situ growth method to form a core-shell nanohybrid (MSN-ICG@PB). Upon a near infrared (NIR) laser excitation, MSN-ICG@PB (200⯵gâ¯mL-1) exhibited highly efficient singlet oxygen (1O2) generation and hyperthermia effect (48.7â). In the presence of exogenous H2O2, PB with peroxidase-like activity promoted the generation of toxic hydroxyl radicals (â¢OH) to achieve chemodynamic therapy (CDT). PTT can greatly increase the permeability of bacterial lipid membrane, facilitating the generated 1O2 and â¢OH to kill bacteria more efficiently. Under NIR irradiation and exogenous H2O2, MSN-ICG@PB (200⯵gâ¯mL-1) with good biocompatibility exhibited a synergistic antibacterial effect against MRSA with high bacterial killing efficiency (>98â¯%). Moreover, due to the synergistic bactericidal mechanism, MSN-ICG@PB with satisfactory biosafety makes it a promising antimicrobial agent to fight against MRSA.
Assuntos
Antibacterianos , Ferrocianetos , Verde de Indocianina , Staphylococcus aureus Resistente à Meticilina , Fotoquimioterapia , Dióxido de Silício , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Verde de Indocianina/química , Verde de Indocianina/farmacologia , Dióxido de Silício/química , Dióxido de Silício/farmacologia , Ferrocianetos/química , Ferrocianetos/farmacologia , Antibacterianos/farmacologia , Antibacterianos/química , Porosidade , Testes de Sensibilidade Microbiana , Terapia Fototérmica , Nanopartículas/química , Propriedades de Superfície , Tamanho da Partícula , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/química , Peróxido de Hidrogênio/farmacologia , Peróxido de Hidrogênio/química , Nanocompostos/química , Raios Infravermelhos , Humanos , AnimaisRESUMO
Intelligent shape memory polymer can be potentially used in manufacturing implantable devices that enables a benign variation of implant dimensions with the external stimuli, thus effectively lowering insertion forces and evading associated risks. However, in surgical implantation, biomaterials-associated infection has imposed a huge burden to healthcare system that urgently requires an efficacious replacement of antibiotic usages. Preventing the initial attachment and harvesting a biocidal function upon native surfaces may be deemed as a preferable strategy to tackle the issues of bacterial infection. Herein, a functionalized polylactic acid (PLA) composite membrane assembled with graphene (GE, a widely used photothermal agent) was fabricated through a blending process and then polydimethylsiloxane utilized as binders to pack hydrophobic SiO2 tightly onto polymer surface (denoted as PLA-GE/SiO2). Such an active platform exhibited a moderate shape-memory performance upon near-infrared (NIR) light stimulation, which was feasible for programmed deformation and shape recovery. Particularly stirring was that PLA-GE/SiO2 exerted a pronounced bacteria-killing effect under NIR illumination, 99.9 % of E. coli and 99.8 % of S. aureus were effectively eradicated in a lean period of 5 min. Furthermore, the obtained composite membrane manifested excellent antiadhesive properties, resulting in a bacteria-repelling efficacy of up to 99 % for both E. coli and S. aureus species. These findings demonstrated the potential value of PLA-GE/SiO2 as a shape-restorable platform in "kill&repel" integration strategy, further expanding its applications for clinical anti-infective treatment.
Assuntos
Antibacterianos , Escherichia coli , Grafite , Testes de Sensibilidade Microbiana , Poliésteres , Staphylococcus aureus , Antibacterianos/farmacologia , Antibacterianos/química , Escherichia coli/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Poliésteres/química , Poliésteres/farmacologia , Grafite/química , Grafite/farmacologia , Dióxido de Silício/química , Dióxido de Silício/farmacologia , Propriedades de Superfície , Membranas Artificiais , Tamanho da Partícula , Aderência Bacteriana/efeitos dos fármacos , Polímeros/química , Polímeros/farmacologia , Raios Infravermelhos , Dimetilpolisiloxanos/química , Dimetilpolisiloxanos/farmacologiaRESUMO
Mesoporous silica nanoparticles were synthesized using a microemulsion-assisted sol-gel method, and calcium, gallium or a combination of both, were used as dopants. The influence of these metallic ions on the physicochemical properties of the nanoparticles was investigated by scanning and transmission electron microscopy, as well as N2 adsorption-desorption methods. The presence of calcium had a significant impact on the morphology and textural features of the nanoparticles. The addition of calcium increased the average diameter of the nanoparticles from 80 nm to 150 nm, while decreasing their specific surface area from 972 m2/g to 344 m2/g. The nanoparticles of all compositions were spheroidal, with a disordered mesoporous structure. An ion release study in cell culture medium demonstrated that gallium was released from the nanoparticles in a sustained manner. In direct contact with concentrations of up to 100 µg/mL of the nanoparticles, gallium-containing nanoparticles did not exhibit cytotoxicity towards pre-osteoblast MC3T3-E1 cells. Moreover, in vitro cell culture tests revealed that the addition of gallium to the nanoparticles enhanced osteogenic activity. Simultaneously, the nanoparticles disrupted the osteoclast differentiation of RAW 264.7 macrophage cells. These findings suggest that gallium-containing nanoparticles possess favorable physicochemical properties and biological characteristics, making them promising candidates for applications in bone tissue regeneration, particularly for unphysiological or pathological conditions such as osteoporosis.
Assuntos
Gálio , Nanopartículas , Osteoclastos , Osteogênese , Gálio/química , Gálio/farmacologia , Animais , Camundongos , Osteoclastos/efeitos dos fármacos , Nanopartículas/química , Osteogênese/efeitos dos fármacos , Dióxido de Silício/química , Dióxido de Silício/farmacologia , Células RAW 264.7 , Porosidade , Diferenciação Celular/efeitos dos fármacosRESUMO
An estimated 1.7 million fatalities and 150 million cases worldwide are attributed to fungal infections annually, that are in rise due to immunocompromised patient population. The challenges posed by traditional treatments can be addressed with the help of nanotechnology advancements. In this study, Co, Cu, and Ag-were doped into silica nanoparticles. Then the synthesized monometallic silica nanohybrids were combined to formulate heterometallic silica nanohybrids, characterized structurally and morphologically, compared, and evaluated for antifungal activity based on their individual and synergistic activity. The antifungal assays were conducted by using ATCC cultures of Candida albicans and QC samples of Trichophyton rubrum, Microsporum gypseum, and Aspergillus niger. The MIC (ranging from 49.00 to 1560.00 µg/mL), MFC (ranging from 197.00 to 3125.00 µg/mL), IC50 values (ranging from 31.10 to 400.80 µg/mL), and FICI of nanohybrids were determined and compared. Moreover, well diffusion assay was performed. ABTS assay and DPPH assay were conducted to investigate the radical scavenging activity (RSA) of nanohybrids. SEM analysis clearly evidenced the structural deformations of each fungal cells and spores due to the treatment with trimetallic nanohybrid. According to the results, the trimetallic silica nanohybrids exhibited the most powerful synergistic RSA and the most effective antifungal activity, compared to the bimetallic silica nanohybrids.
Assuntos
Antifúngicos , Candida albicans , Testes de Sensibilidade Microbiana , Dióxido de Silício , Antifúngicos/farmacologia , Antifúngicos/química , Antifúngicos/síntese química , Dióxido de Silício/química , Dióxido de Silício/farmacologia , Candida albicans/efeitos dos fármacos , Aspergillus niger/efeitos dos fármacos , Nanopartículas/química , Microsporum/efeitos dos fármacos , Sinergismo Farmacológico , Cobre/química , Cobre/farmacologia , Prata/farmacologia , Prata/química , ArthrodermataceaeRESUMO
AIMS: In this study, the antifungal efficacy and phytotoxicity of silica coated porous zinc oxide nanoparticle (SZNP) were analyzed as this nanocomposite was observed to be a suitable platform for slow release fungicides and has the promise to bring down the dosage of other agrochemicals as well. METHODS AND RESULTS: Loading and release kinetics of tricyclazole, a potent fungicide, were analyzed by measuring surface area (SBET) using Brunauer-Emmett-Teller (BET) isotherm and liquid chromatography tandem mass spectrometry (LC-MS/MS), respectively. The antifungal efficacy of ZnO nanoparticle (ZNP) and SZNP was investigated on two phytopathogenic fungi (Alternaria solani and Aspergillus niger). The morphological changes to the fungal structure due to ZNP and SZNP treatment were studied by field emission-scanning electron microscopy. Nanoparticle mediated elevation of reactive oxygen species (ROS) in fungal samples was detected by analyzing the levels of superoxide dismutase, catalase, thiol content, lipid peroxidation, and by 2,7-dichlorofluorescin diacetate assay. The phytotoxicity of these two nanostructures was assessed in rice plants by measuring primary plant growth parameters. Further, the translocation of the nanocomposite in the same plant model system was examined by checking the presence of fluorescein isothiocyanate tagged SZNP within the plant tissue. CONCLUSIONS: ZNP had superior antifungal efficacy than SZNP and caused the generation of more ROS in the fungal samples. Even then, SZNP was preferred as an agrochemical delivery vehicle because, unlike ZNP alone, it was not toxic to plant system. Moreover, as silica in nanoform is entomotoxic in nature and nano ZnO has antifungal property, both the cargo (agrochemical) and the carrier system (silica coated porous nano zinc oxide) will have a synergistic effect in crop protection.
Assuntos
Antifúngicos , Nanocompostos , Dióxido de Silício , Óxido de Zinco , Óxido de Zinco/farmacologia , Nanocompostos/toxicidade , Dióxido de Silício/farmacologia , Dióxido de Silício/química , Antifúngicos/farmacologia , Agroquímicos/farmacologia , Aspergillus niger/efeitos dos fármacos , Aspergillus niger/crescimento & desenvolvimento , Oryza/microbiologia , Oryza/crescimento & desenvolvimento , Oryza/efeitos dos fármacos , Fungicidas Industriais/farmacologia , Porosidade , Doenças das Plantas/microbiologia , Doenças das Plantas/prevenção & controle , Preparações de Ação Retardada , Espécies Reativas de Oxigênio/metabolismoRESUMO
Periodontitis, a prevalent chronic inflammatory disease worldwide, is triggered by periodontopathogenic bacteria, resulting in the progressive destruction of periodontal tissue, particularly the alveolar bone. To effectively address periodontitis, this study proposed a nanoformulation known as CuS@MSN-SCS. This formulation involves coating citrate-grafted copper sulfide (CuS) nanoparticles with mesoporous silica (MSNs), followed by surface modification using amino groups and sulfated chitosan (SCS) through electrostatic interactions. The objective of this formulation is to achieve efficient bacteria removal by inducing ROS signaling pathways mediated by Cu2+ ions. Additionally, it aims to promote alveolar bone regeneration through Cu2+-induced pro-angiogenesis and SCS-mediated bone regeneration. As anticipated, by regulating the surface charges, the negatively charged CuS nanoparticles capped with sodium citrate were successfully coated with MSNs, and the subsequent introduction of amine groups using (3-aminopropyl)triethoxysilane was followed by the incorporation of SCS through electrostatic interactions, resulting in the formation of CuS@MSN-SCS. The developed nanoformulation was verified to not only significantly exacerbate the oxidative stress of Fusobacterium nucleatum, thereby suppressing bacteria growth and biofilm formation in vitro, but also effectively alleviate the inflammatory response and promote alveolar bone regeneration without evident biotoxicity in an in vivo rat periodontitis model. These findings contribute to the therapeutic effect on periodontitis. Overall, this study successfully developed a nanoformulation for combating bacteria and facilitating alveolar bone regeneration, demonstrating the promising potential for clinical treatment of periodontitis.
Assuntos
Antibacterianos , Regeneração Óssea , Quitosana , Cobre , Fusobacterium nucleatum , Nanopartículas , Periodontite , Quitosana/química , Quitosana/farmacologia , Periodontite/tratamento farmacológico , Periodontite/microbiologia , Periodontite/terapia , Periodontite/patologia , Animais , Antibacterianos/farmacologia , Antibacterianos/química , Regeneração Óssea/efeitos dos fármacos , Ratos , Cobre/química , Cobre/farmacologia , Fusobacterium nucleatum/efeitos dos fármacos , Nanopartículas/química , Ratos Sprague-Dawley , Masculino , Sulfatos/química , Sulfatos/farmacologia , Dióxido de Silício/química , Dióxido de Silício/farmacologia , Testes de Sensibilidade MicrobianaRESUMO
In this paper, a simple, bottom up, bioinspired technique is proposed for the synthesis of highly stable colloids of silica supported spherical silver nanoparticles (SiO2@Ag) that act as efficient catalytic and antimicrobial coatings for an organic substrate, filter paper. The core - shell structure and the highly branched dendritic polymer, poly(ethylene)imine, enabled the precise control of growth rate and morphology of silica and silver nanoparticles. The polymer also enabled the deposition of these nanoparticles onto an organic substrate, filter paper, through immersion by modifying its surface. The catalytic and antibacterial properties of these samples were assessed. The results obtained from this analysis showed a complete degradation of an aqueous pollutant, 4-nitrophenol, for 6 successive catalytic cycles without intermediate purification steps. Furthermore, the polymeric silica-silver suspension proved to express antibacterial activity against both Gram-positive and Gram-negative bacteria (Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa). The antibacterial properties were evaluated according to the disk diffusion method, whereas the Minimum Inhibitory Concentration was also determined. The samples were examined by Scanning Electron Microscopy, Transmission Electron Microscopy, X-ray diffraction analysis, z-potential analysis, Fourier Transform Infrared Spectroscopy and Ultraviolet-visible Spectroscopy.
Assuntos
Antibacterianos , Coloides , Testes de Sensibilidade Microbiana , Dióxido de Silício , Prata , Prata/química , Prata/farmacologia , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/síntese química , Dióxido de Silício/química , Dióxido de Silício/farmacologia , Catálise , Coloides/química , Nanopartículas Metálicas/química , Polímeros/química , Polímeros/farmacologia , Polímeros/síntese química , Escherichia coli/efeitos dos fármacos , Escherichia coli/crescimento & desenvolvimento , Papel , Staphylococcus aureus/efeitos dos fármacos , Pseudomonas aeruginosa/efeitos dos fármacos , Propriedades de Superfície , Tamanho da Partícula , Nitrofenóis/químicaRESUMO
In recent decades, extensive research has been directed toward mitigating microbial contamination and preventing biofilm formation. However, many conventional antibiofilm methods rely on hazardous and toxic substances, neglecting potential risks to human health and the environment. Moreover, these approaches often rely on single-strategy mechanisms, utilizing either bactericidal or fouling-resistant agents, which have shown limited efficacy in long-term biofilm suppression. In this study, we propose an efficient and sustainable biofilm-resistant slippery hybrid slippery composite. This composite integrates nontoxic and environmentally friendly materials including chitosan, silicone oil-infused polydimethylsiloxane, and mesoporous silica nanoparticles in a synergistic manner. Leveraging the bacteria-killing properties of chitosan and the antifouling capabilities of the silicone oil layer, the hybrid composite exhibits robust antibiofilm performance against both Gram-positive and Gram-negative bacteria. Furthermore, the inclusion of mesoporous silica nanoparticles enhances the oil absorption capacity and self-replenishing properties, ensuring exceptional biofilm inhibition even under harsh conditions such as exposure to high shear flow and prolonged incubation (7 days). This approach offers promising prospects for developing effective biofilm-resistant materials with a reduced environmental impact and improved long-term performance.
Assuntos
Antibacterianos , Biofilmes , Quitosana , Dimetilpolisiloxanos , Nanopartículas , Dióxido de Silício , Biofilmes/efeitos dos fármacos , Quitosana/química , Quitosana/farmacologia , Dióxido de Silício/química , Dióxido de Silício/farmacologia , Nanopartículas/química , Antibacterianos/farmacologia , Antibacterianos/química , Porosidade , Dimetilpolisiloxanos/química , Dimetilpolisiloxanos/farmacologia , Testes de Sensibilidade MicrobianaRESUMO
Physicochemical properties of nanoparticles, such as particle size, surface charge, and particle shape, have a significant impact on cell activities. However, the effects of surface functionalization of nanoparticles with small chemical groups on stem cell behavior and function remain understudied. Herein, we incorporated different chemical functional groups (amino, DETA, hydroxyl, phosphate, and sulfonate with charges of +9.5, + 21.7, -14.1, -25.6, and -37.7, respectively) to the surface of inorganic silica nanoparticles. To trace their effects on mesenchymal stem cells (MSCs) of rat bone marrow, these functionalized silica nanoparticles were used to encapsulate Rhodamine B fluorophore dye. We found that surface functionalization with positively charged and short-chain chemical groups facilitates cell internalization and retention of nanoparticles in MSCs. The endocytic pathway differed among functionalized nanoparticles when tested with ion-channel inhibitors. Negatively charged nanoparticles mainly use lysosomal exocytosis to exit cells, while positively charged nanoparticles can undergo endosomal escape to avoid scavenging. The cytotoxic profiles of these functionalized silica nanoparticles are still within acceptable limits and tolerable. They exerted subtle effects on the actin cytoskeleton and migration ability. Last, phosphate-functionalized nanoparticles upregulate osteogenesis-related genes and induce osteoblast-like morphology, implying that it can direct MSCs lineage specification for bone tissue engineering. Our study provides insights into the rational design of biomaterials for effective drug delivery and regenerative medicine.
Assuntos
Materiais Biocompatíveis , Teste de Materiais , Células-Tronco Mesenquimais , Nanopartículas , Tamanho da Partícula , Dióxido de Silício , Propriedades de Superfície , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Dióxido de Silício/química , Dióxido de Silício/farmacologia , Nanopartículas/química , Animais , Ratos , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Osteogênese/efeitos dos fármacosRESUMO
Poor hemostatic ability and less vascularization at the injury site could hinder wound healing as well as adversely affect the quality of life (QOL). An ideal wound dressing should exhibit certain characteristics: (a) good hemostatic ability, (b) rapid wound healing, and (c) skin appendage formation. This necessitates the advent of innovative dressings to facilitate skin regeneration. Therapeutic ions, such as silicon ions (Si4+) and calcium ions (Ca2+), have been shown to assist in wound repair. The Si4+ released from silica (SiO2) can upregulate the expression of proteins, including the vascular endothelial growth factor (VEGF) and alpha smooth muscle actin (α-SMA), which is conducive to vascularization; Ca2+ released from tricalcium phosphate (TCP) can promote the coagulation alongside upregulating the expression of cell migration and cell differentiation related proteins, thereby facilitating the wound repair. The overarching objective of this study was to exploit short SiO2 nanofibers along with the TCP to prepare TCPx@SSF aerogels and assess their wound healing ability. Short SiO2 nanofibers were prepared by electrospinning and blended with varying proportions of TCP to afford TCPx@SSF aerogel scaffolds. The TCPx@SSF aerogels exhibited good cytocompatibility in a subcutaneous implantation model and manifested a rapid hemostatic effect (hemostatic time 75 s) in a liver trauma model in the rabbit. These aerogel scaffolds also promoted skin regeneration and exhibited rapid wound closure, epithelial tissue regeneration, and collagen deposition. Taken together, TCPx@SSF aerogels may be valuable for wound healing.
Assuntos
Fosfatos de Cálcio , Nanofibras , Dióxido de Silício , Alicerces Teciduais , Cicatrização , Nanofibras/química , Animais , Coelhos , Dióxido de Silício/química , Dióxido de Silício/farmacologia , Fosfatos de Cálcio/química , Fosfatos de Cálcio/farmacologia , Cicatrização/efeitos dos fármacos , Alicerces Teciduais/química , Pele/efeitos dos fármacos , Regeneração/efeitos dos fármacos , Camundongos , Géis/químicaRESUMO
Recently, bacterial infections have become a global crisis, greatly threatening the health of human beings. The development of a non-antibiotic biomaterial is recognized as an alternative way for the effective treatment of bacterial infections. In the present work, a multifunctional copper peroxide (CP) nanodot-decorated gold nanostar (GNS)/silica nanorod (SiNR) Janus nanostructure (GNS@CP/SiNR) with excellent antibacterial activity was reported. Due to the formation of the Janus nanostructure, GNS@CP/SiNR displayed strong plasmonic resonance absorbance in the near infrared (NIR)-II region that enabled the nanosystem to achieve mild photothermal therapy (MPTT). In acidic conditions, CP decorated on GNS@CP/SiNR dissociated rapidly by releasing Cu2+ and H2O2, which subsequently transformed to ËOH via the Fenton-like reaction for chemodynamic therapy (CDT). As a result, GNS@CP/SiNR could effectively inhibit both Gram-negative Escherichia coli (E. coli) and Gram-positive Staphylococcus aureus (S. aureus), and eradicate the associated bacterial biofilms by exerting the synergistic MPTT/CDT antibacterial effect. Moreover, GNS@CP/SiNR was also demonstrated to be effective in treating wound infections, as verified on the S. aureus-infected full thickness excision wound rat model. Our mechanism study revealed that the synergistic MPTT/CDT effect of GNS@CP/SiNR firstly caused bacterial membrane damage, followed by boosting intracellular ROS via the severe oxidative stress effect, which subsequently caused the depletion of intracellular GSH and DNA damage, finally leading to the death of bacteria.
Assuntos
Antibacterianos , Cobre , Escherichia coli , Ouro , Radical Hidroxila , Nanotubos , Dióxido de Silício , Staphylococcus aureus , Ouro/química , Ouro/farmacologia , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/síntese química , Animais , Staphylococcus aureus/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Nanotubos/química , Radical Hidroxila/metabolismo , Radical Hidroxila/química , Cobre/química , Cobre/farmacologia , Dióxido de Silício/química , Dióxido de Silício/farmacologia , Ratos , Infecção dos Ferimentos/tratamento farmacológico , Infecção dos Ferimentos/microbiologia , Terapia Fototérmica , Raios Infravermelhos , Testes de Sensibilidade Microbiana , Nanopartículas Metálicas/química , Ratos Sprague-Dawley , Biofilmes/efeitos dos fármacosRESUMO
The metastasis and recurrence of cancer are related to immunosuppression and hypoxia in the tumor microenvironment. Activating immune activity and improving the hypoxic environment face essential challenges. This paper reports on a multifunctional nanomaterial, HSCCMBC, that induces immunogenic cell death through powerful photodynamic therapy/chemodynamic therapy synergistic antitumor effects. The tumor microenvironment changed from the immunosuppressive type to immune type, activated the immune activity of the system, decomposed hydrogen peroxide to generate oxygen based on Fenton-like reaction, and effectively increased the level of intracellular O2 with the assistance of 3-bromopyruvate, a cell respiratory inhibitor. The structure and composition of HSCCMBC were characterized by transmission electron microscopy, X-ray photoelectron spectroscopy, X-ray diffraction, infrared spectroscopy, etc. Oxygen probe RDPP was used to investigate the oxygen level inside and outside the cell, and hydroxyl radical probe tetramethylbenzidine was used to investigate the Fenton-like reaction ability. The immunofluorescence method investigated the expression of various immune markers and hypoxia-inducing factors in vitro and in vivo after treatment. In vitro and in vivo experiments indicate that HSCCMBC is an excellent antitumor agent and is expected to be a candidate drug for antitumor immunotherapy.
Assuntos
Nanopartículas , Neoplasias , Humanos , Dióxido de Silício/farmacologia , Cobre/química , Carbono/farmacologia , Morte Celular Imunogênica , Neoplasias/tratamento farmacológico , Oxigênio/química , Hipóxia , Linhagem Celular Tumoral , Peróxido de Hidrogênio/química , Microambiente Tumoral , Nanopartículas/químicaRESUMO
In this study, amino-functionalized mesoporous silica/hydroxyapatite nanoparticles (MSNS/HAP) with the property of acid dissociation have been prepared as a traditional Chinese medicine monomer carriers to improve the drug loading rate and antibacterial properties of antimicrobial quercetin (QUE) in vitro. The experimental results confirm that the drug loading rate of MSNs/HAP is 28.94 %, which is about 3.6 times higher than that of aminated mesoporous sililca nanoparticles (MSNs). The drug release of QUE on MSNs/HAP is pH-sensitive in phosphate buffered saline (pH=4.0-7.4). The above fabricated traditional Chinese medicine monomer modified nanocomposites (QUE@MSNs/HAP) displays concentration-dependent inhibitory effect, which shows better antibacterial effect than free QUE. The minimum inhibitory concentration for two tested bacteria, Staphylococcus aureus (S.aureus) and Escherichia coli (E.coli), is 256 mg·L -1. In summary, QUE@MSNs/HAP have successfully prepared, which not only improves the bio-availability of QUE, but also has acid-sensitive drug release properties. Compared with free QUE, its antibacterial performance significantly enhances, which provides a theoretical basis for the application of Chinese medicine molecules in bacterial treatment.
Assuntos
Durapatita , Nanopartículas , Quercetina/farmacologia , Dióxido de Silício/farmacologia , Antibacterianos/farmacologia , Porosidade , Portadores de FármacosRESUMO
This study aims at understanding the effect of the photoreduction process during the synthesis of gold (Au)-doped TiO2 colloids on the conferred functionalities on cotton fabrics. TiO2/Au and TiO2/Au/SiO2 colloids were synthesized through the sol-gel method with and without undergoing the photoreduction step based on different molar ratios of Au:Ti (0.001 and 0.01) and TiO2/SiO2 (1:1 and 1:2.3). The colloids were applied to cotton fabrics, and the obtained photocatalytic self-cleaning, wet photocatalytic activity, UV protection, and antibacterial activity against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) bacteria were investigated. The obtained results demonstrated that the photoreduction of Au weakened the self-cleaning effect and reduced the photocatalytic activity of coated fabrics. Also, an excess amount of Au deteriorated the photocatalytic activity under both UV and visible light. The most efficient self-cleaning effect was obtained on fabrics coated with a ternary TiO2/Au/SiO2 colloid containing ionic Au, where it decomposed coffee and red-wine stains after 3 h of illumination. Adding silica (SiO2) made the fabrics superhydrophilic and led to greater methylene blue (MB) dye adsorption, a faster dye degradation pace, and more efficient stain removal. Moreover, the photoreduction process affected the size of Au nanoparticles (NPs), weakened the antibacterial activity of fabrics against both types of tested bacteria, and modestly increased the UV protection. In general, the photoactivity of Au-doped colloids was influenced by the synthesis method, the ionic and metallic states of the Au dopant, the concentration of the Au dopant, and the presence and concentration of silica.
Assuntos
Antibacterianos , Coloides , Fibra de Algodão , Escherichia coli , Ouro , Staphylococcus aureus , Titânio , Titânio/química , Titânio/farmacologia , Antibacterianos/farmacologia , Antibacterianos/química , Ouro/química , Ouro/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Coloides/química , Dióxido de Silício/química , Dióxido de Silício/farmacologia , Catálise , Raios Ultravioleta , OxirreduçãoRESUMO
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.