RESUMEN
Biofilm-associated infections (BAIs) continue to pose a major challenge in the medical field. Nanomedicine, in particular, promises significant advances in combating BAIs through the introduction of a variety of nanomaterials and nano-antimicrobial strategies. However, studies to date have primarily focused on the removal of the bacterial biofilm and neglect the subsequent post-biofilm therapeutic measures for BAIs, rendering pure anti-biofilm strategies insufficient for the holistic recovery of affected patients. Herein, we construct an emerging dual-functional composite nanosheet (SiHx@Ga) that responds to pHs fluctuation in the biofilm microenvironment to enable a sequential therapy of BAIs. In the acidic environment of biofilm, SiHx@Ga employs the self-sensitized photothermal Trojan horse strategy to effectively impair the reactive oxygen species (ROS) defense system while triggering oxidative stress and lipid peroxidation of bacteria, engendering potent antibacterial and anti-biofilm effects. Surprisingly, in the post-treatment phase, SiHx@Ga adsorbs free pathogenic nucleic acids released after biofilm destruction, generates hydrogen with ROS-scavenging and promotes macrophage polarization to the M2 type, effectively mitigating damaging inflammatory burst and promoting tissue healing. This well-orchestrated strategy provides a sequential therapy of BAIs by utilizing microenvironmental variations, offering a conceptual paradigm shift in the field of nanomedicine anti-infectives.
Asunto(s)
Antibacterianos , Biopelículas , Galio , Especies Reactivas de Oxígeno , Biopelículas/efectos de los fármacos , Animales , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Especies Reactivas de Oxígeno/metabolismo , Galio/química , Galio/farmacología , Ratones , Portadores de Fármacos/química , Células RAW 264.7 , Humanos , Staphylococcus aureus/efectos de los fármacos , Staphylococcus aureus/fisiologíaRESUMEN
A new type of hybrid polymer particles capable of carrying the cytostatic drug doxorubicin and labeled with a gallium compound was prepared. These microparticles consist of a core and a hydrogel shell, which serves as the structural matrix. The shell can be employed to immobilize gallium oxide hydroxide (GaOOH) nanoparticles and the drug, resulting in hybrid beads with sizes of approximately 3.81 ± 0.09 µm. The microparticles exhibit the ability to incorporate a remarkably large amount of doxorubicin, approximately 0.96 mg per 1 mg of the polymeric carrier. Additionally, GaOOH nanoparticles can be deposited within the hydrogel layer at an amount of 0.64 mg per 1 mg of the carrier. These nanoparticles, resembling rice grains with an average size of 593 nm by 155 nm, are located on the surface of the polymer carrier. In vitro studies on breast and colon cancer cell lines revealed a pronounced cytotoxic effect of the hybrid polymer particles loaded with doxorubicin, indicating their potential for cancer therapies. Furthermore, investigations on doping the hybrid particles with the Ga-68 radioisotope demonstrated their potential application in positron emission tomography (PET) imaging. The proposed structures present a promising theranostic platform, where particles could be employed in anticancer therapies while monitoring their accumulation in the body using PET.
Asunto(s)
Doxorrubicina , Galio , Hidrogeles , Nanopartículas , Doxorrubicina/química , Doxorrubicina/farmacología , Doxorrubicina/administración & dosificación , Humanos , Galio/química , Nanopartículas/química , Hidrogeles/química , Portadores de Fármacos/química , Línea Celular Tumoral , Radioisótopos de Galio/química , Tomografía de Emisión de Positrones , Hidróxidos/química , Supervivencia Celular/efectos de los fármacos , Tamaño de la PartículaRESUMEN
Osteosarcoma (OS) is the mostly commonly occurring primary bone cancer. Despite comprehensive treatment programs including neoadjuvant chemotherapy and tumour resection, survival rates have not improved significantly since the 1970s. Survival rates are dramatically reduced for patients who suffer a local recurrence. Furthermore, primary bone cancer patients are at increased risk of bone fractures. Consequently, there is an urgent need for alternative treatment options. In this paper we report the development of novel gallium doped bioactive glass that selectively kill bone cancer cells whilst simultaneously stimulating new bone growth. Here we show, using a combination of 3-(4.5-dimethylthiazol-2-yl)-2.5-diphenyltetrazolium bromide, LIVE/DEAD assays and image analysis, that bioactive glasses containing gallium oxide are highly toxic and reduce both the proliferation and migration of bone cancer cells (Saos-2) in a dose dependant manner. Glasses containing 5 mol% gallium oxide reduced the viability of OS cells by 99% without being cytotoxic to the non-cancerous normal human osteoblasts (NHOst) control cells. Furthermore, Fourier transform infrared and energy-dispersive x-ray spectroscopy results confirmed the formation of an amorphous calcium phosphate/hydroxyapatite like layer on the surface of the bioactive glass particulates, after 7 d incubating in simulated body fluid, indicating the early stages of bone formation. These materials show significant potential for use in bone cancer applications as part of a multimodal treatment.
Asunto(s)
Antineoplásicos , Neoplasias Óseas , Proliferación Celular , Supervivencia Celular , Galio , Vidrio , Osteosarcoma , Humanos , Galio/química , Osteosarcoma/tratamiento farmacológico , Antineoplásicos/farmacología , Antineoplásicos/química , Vidrio/química , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Neoplasias Óseas/tratamiento farmacológico , Espectroscopía Infrarroja por Transformada de Fourier , Osteoblastos/efectos de los fármacos , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Movimiento Celular/efectos de los fármacos , Sistemas de Liberación de Medicamentos , Ensayo de MaterialesRESUMEN
Controlling multidrug-resistant microorganisms (MRM) has a long history with the extensive and inappropriate use of antibiotics. At the cost of these drugs being scarce, new possibilities have to be explored to inhibit the growth of microorganisms. Thus, metallic compounds have shown to be promising as a viable alternative to contain pathogens resistant to conventional antimicrobials. Gallium (Ga3+) can be highlighted, which is an antimicrobial agent capable of disrupting the essential activities of microorganisms, such as metabolism, cellular respiration and DNA synthesis. It was observed that this occurs due to the similar properties between Ga3+ and iron (Fe3+), which is a fundamental ion for the correct functioning of bacterial activities. The mimetic effect performed by Ga3+ prevents iron transporters from distinguishing both ions and results in the substitution of Fe3+ for Ga3+ and in adverse metabolic disturbances in rapidly growing cells. This review focuses on analyzing the development of research involving Ga3+, elucidating the intracellular incorporation of the "Trojan Horse", summarizing the mechanism of interaction between gallium and iron and comparing the most recent and broad-spectrum studies using gallium-based compounds with antimicrobial scope.
Asunto(s)
Bacterias , Galio , Hierro , Galio/farmacología , Galio/metabolismo , Hierro/metabolismo , Bacterias/efectos de los fármacos , Bacterias/metabolismo , Antibacterianos/farmacología , Humanos , Pruebas de Sensibilidad Microbiana , Antiinfecciosos/farmacología , Antiinfecciosos/metabolismoRESUMEN
Porphyromonas gingivalis has been demonstrated to have the strongest association with periodontitis. Within the host, P. gingivalis relies on acquiring iron and heme through the aggregation and lysis of erythrocytes, which are important factors in the growth and virulence of P. gingivalis. Additionally, the excess obtained heme is deposited on the surface of P. gingivalis, protecting the cells from oxidative damage. Based on these biological properties of the interaction between P. gingivalis and erythrocytes, this study developed an erythrocyte membrane nanovesicle loaded with gallium porphyrins to mimic erythrocytes. The nanovesicle can target and adhere with P. gingivalis precisely, being lysed and utilized by P. gingivalis as erythrocytes. Ingested gallium porphyrin replaces iron porphyrin in P. gingivalis, causing intracellular metabolic disruption. Deposited porphyrin generates a large amount of reactive oxygen species (ROS) under blue light, causing oxidative damage, and its lethality is enhanced by bacterial metabolic disruption, synergistically killing P. gingivalis. Our results demonstrate that this strategy can target and inhibit P. gingivalis, reduce its invasion of epithelial cells, and alleviate the progression of periodontitis.
Asunto(s)
Eritrocitos , Periodontitis , Porfirinas , Porphyromonas gingivalis , Porphyromonas gingivalis/efectos de los fármacos , Porphyromonas gingivalis/metabolismo , Porphyromonas gingivalis/química , Periodontitis/microbiología , Periodontitis/tratamiento farmacológico , Periodontitis/patología , Eritrocitos/efectos de los fármacos , Eritrocitos/metabolismo , Humanos , Porfirinas/química , Porfirinas/farmacología , Animales , Especies Reactivas de Oxígeno/metabolismo , Galio/química , Galio/farmacología , Ratones , Antibacterianos/farmacología , Antibacterianos/química , Materiales Biomiméticos/química , Materiales Biomiméticos/farmacologíaRESUMEN
Microorganisms of the ESKAPE group pose an enormous threat to human well-being, thus requiring a multidisciplinary approach for discovering novel drugs that are not only effective but utilize an innovative mechanism of action in order to decrease fast developing resistance. A promising but still hardly explored implementation in the "Trojan horse" antibacterial strategy has been recognized in gallium, an iron mimicry species with no known function but exerting a bacteriostatic/bactericidal effect against some representatives of the group. The study herewith focuses on the bacterium A. baumannii and its siderophore acinetobactin in its two isomeric forms depending on the acidity of the medium. By applying the powerful tools of the DFT approach, we aim to delineate those physicochemical characteristics that are of great importance for potentiating gallium's ability to compete with the native ferric cation for binding acinetobactin such as pH, solvent exposure (dielectric constant of the environment), different metal/siderophore ratios, and complex composition. Hence, the provided results not only furnish some explanation of the positive effect of three Ga3+-based anti-infectives in terms of metal cation competition but also shed light on reported in vitro and in vivo observations at a molecular level in regard to gallium's antibacterial effect against A. baumannii.
Asunto(s)
Acinetobacter baumannii , Antibacterianos , Teoría Funcional de la Densidad , Galio , Pruebas de Sensibilidad Microbiana , Galio/química , Galio/farmacología , Acinetobacter baumannii/efectos de los fármacos , Antibacterianos/farmacología , Antibacterianos/química , Antibacterianos/síntesis química , Complejos de Coordinación/farmacología , Complejos de Coordinación/química , Complejos de Coordinación/síntesis química , Oxazoles/química , Oxazoles/farmacología , Estructura Molecular , Imidazoles/química , Imidazoles/farmacologíaRESUMEN
Iron metabolism has emerged as a promising target for cancer therapy; however, the innate metabolic compensatory capacity of cancer cells significantly limits the effectiveness of iron metabolism therapy. Herein, bioactive gallium sulfide nanodots (GaSx), with dual functions of "reprogramming" and "interfering" iron metabolic pathways, were successfully developed for tumor iron metabolism therapy. The constructed GaSx nanodots ingeniously harness hydrogen sulfide (H2S) gas, which is released in response to the tumor microenvironment, to reprogram the inherent transferrin receptor 1 (TfR1)-ferroportin 1 (FPN1) iron metabolism axis in cancer cells. Concurrently, the gallium ions (Ga3+) derived from GaSx act as a biochemical "Trojan horse", mimicking the role of iron and displacing it from essential biomolecular binding sites, thereby influencing the fate of cancer cells. By leveraging the dual mechanisms of Ga3+-mediated iron disruption and H2S-facilitated reprogramming of iron metabolic pathways, GaSx prompted the initiation of a paraptosis-apoptosis hybrid pathway in cancer cells, leading to marked suppression of tumor proliferation. Importantly, the dysregulation of iron metabolism induced by GaSx notably increased tumor cell susceptibility to both chemotherapy and immune checkpoint blockade (ICB) therapy. This study underscores the therapeutic promise of gas-based interventions and metal ion interference strategies for the tumor metabolism treatment.
Asunto(s)
Apoptosis , Galio , Hierro , Paraptosis , Animales , Humanos , Ratones , Antineoplásicos/farmacología , Antineoplásicos/química , Apoptosis/efectos de los fármacos , Proteínas de Transporte de Catión , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Galio/química , Galio/farmacología , Sulfuro de Hidrógeno/metabolismo , Sulfuro de Hidrógeno/química , Sulfuro de Hidrógeno/farmacología , Hierro/metabolismo , Hierro/química , Neoplasias/tratamiento farmacológico , Neoplasias/metabolismo , Neoplasias/patología , Paraptosis/efectos de los fármacos , Receptores de Transferrina/metabolismo , Sulfuros/química , Sulfuros/farmacología , Microambiente Tumoral/efectos de los fármacosRESUMEN
Novel anticancer strategies reduce side effects on healthy tissues by elevating the lethal abilities of cancer cells. The development of effective particles with good bioavailability and selectivity remains problematic. For undesirable features, green chemistry is used to synthesize the best compounds, or natural-based particles are improved. Photodynamic therapy (PDT), modelled on phthalocyanines (Pcs), still delivers second-generation sensitizers which are complemented with metal ions, such as Zn2+, Al3+, or Ga3+. Gallium octacarboxyphthalocyanine hydroxide (Ga(OH)PcOC), was designed for skin cancer treatment, and was used as a pro-apoptotic and pro-oxidative agent on normal skin cell lines, fibroblasts (NHDF), and keratinocytes (HaCaT), with promising selectivity against melanoma cancer cells (Me45) in vitro. Compared to the previous reported findings, where the ZnPcOC acted on the skin cell lines at higher doses, the sensitivities to the Ga(OH)PcOC allows for an effective reduction of the sensitizer dose. The effective dose, for a novel Ga(OH)PcOC particle, was significantly reduced from 30 µM to 6 µM on Me45 cancer cells, tested using 24 h MTT viability, as well as cytometric pro-oxidative and pro-apoptotic assays. The promising photosensitizer did not reduce viability in normal fibroblasts and keratinocytes without reactive oxygen species (ROS) elevation or apoptosis induction. The improvement to the previous findings is better Ga-based photosensitizer selectivity against the cancer Me45 cells, then observed in Zn-based compounds.
Asunto(s)
Antineoplásicos , Apoptosis , Ensayos de Selección de Medicamentos Antitumorales , Galio , Indoles , Fármacos Fotosensibilizantes , Neoplasias Cutáneas , Humanos , Apoptosis/efectos de los fármacos , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/síntesis química , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/química , Fármacos Fotosensibilizantes/síntesis química , Neoplasias Cutáneas/tratamiento farmacológico , Neoplasias Cutáneas/patología , Galio/química , Galio/farmacología , Estructura Molecular , Indoles/química , Indoles/farmacología , Indoles/síntesis química , Isoindoles/farmacología , Isoindoles/química , Isoindoles/síntesis química , Fotoquimioterapia , Relación Dosis-Respuesta a Droga , Supervivencia Celular/efectos de los fármacos , Relación Estructura-Actividad , Proliferación Celular/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Hidróxidos/química , Hidróxidos/farmacologíaRESUMEN
Considering the excellent properties such as deep tissue penetration, high signal-to-noise ratio, and in-situ recharge and reactivation, near-infrared luminescence long afterglow nanoparticles show considerable promise for biological application, especially in multifunctional imaging, targeting, and synergistic therapeutic. In this paper, Zn3Ga4GeO11: 0.1 % Cr3+, 1 % Yb3+, 0.1 % Tm3+@Ag-FA (ZGGO@Ag-FA, ZGA-FA) nanoparticles were synthesized by in-situ growth of Ag nanoparticles on the surface of long afterglow nanoparticles, and further modified with folic acid. Through precise adjustments, the luminescent properties of ZnGa2O4 were enhanced and notably boosted the photothermal effect of Ag by leveraging the upconversion emission of ZGGO, with a photothermal conversion efficiency reaching about 59.9 %. The ZGA-FA nanoparticles are ultra-small, measuring less than 50 nm. The modification with folic acid provides the ZGA-FA nanoparticles with excellent tumor-targeting capabilities, demonstrating effective enrichment and retention in tumor tissues, thus enabling long-term imaging and therapy through in vivo re-excitation. Due to its stable photothermal effect, outstanding near-infrared (NIR) afterglow imaging, and red-light charged characteristics, combined with effective tumor-targeting abilities, the therapeutic strategy proposed by this study has significant potential for clinical applications.
Asunto(s)
Ácido Fólico , Animales , Humanos , Ratones , Ácido Fólico/química , Imagen Óptica , Plata/química , Galio/química , Nanopartículas del Metal/química , Terapia Fototérmica , Nanopartículas/química , Ratones Endogámicos BALB C , Neoplasias/diagnóstico por imagen , Neoplasias/tratamiento farmacológico , Neoplasias/terapia , Antineoplásicos/química , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Fototerapia , Ratones DesnudosRESUMEN
The intratumor microbiome imbalance in pancreatic cancer promotes a tolerogenic immune response and triggers immunotherapy resistance. Here we show that Lactobacillus rhamnosus GG probiotics, outfitted with a gallium-polyphenol network (LGG@Ga-poly), bolster immunotherapy in pancreatic cancer by modulating microbiota-immune interactions. Upon oral administration, LGG@Ga-poly targets pancreatic tumors specifically, and selectively eradicates tumor-promoting Proteobacteria and microbiota-derived lipopolysaccharides through a gallium-facilitated disruption of bacterial iron respiration. This elimination of intratumor microbiota impedes the activation of tumoral Toll-like receptors, thus reducing immunosuppressive PD-L1 and interleukin-1ß expression by tumor cells, diminishing immunotolerant myeloid populations, and improving the infiltration of cytotoxic T lymphocytes in tumors. Moreover, LGG@Ga-poly hampers pancreatic tumor growth in both preventive and therapeutic contexts, and amplifies the antitumor efficacy of immune checkpoint blockade in preclinical cancer models in female mice. Overall, we offer evidence that thoughtfully designed biomaterials targeting intratumor microbiota can efficaciously augment immunotherapy for the challenging pancreatic cancer.
Asunto(s)
Galio , Lacticaseibacillus rhamnosus , Microbiota , Neoplasias Pancreáticas , Polifenoles , Probióticos , Neoplasias Pancreáticas/inmunología , Neoplasias Pancreáticas/terapia , Neoplasias Pancreáticas/microbiología , Animales , Probióticos/administración & dosificación , Ratones , Femenino , Humanos , Lacticaseibacillus rhamnosus/inmunología , Polifenoles/farmacología , Microbiota/inmunología , Microbiota/efectos de los fármacos , Línea Celular Tumoral , Inmunoterapia/métodos , Ratones Endogámicos C57BL , Antígeno B7-H1/metabolismo , Antígeno B7-H1/inmunología , Linfocitos T Citotóxicos/inmunologíaRESUMEN
Hypochlorite (ClO-) and gallium (â ¢) ions (Ga3+) have extensive applications in various human industries and daily activities. However, their inherent toxicity poses significant risks to environmental preservation and human well-being. Hence, the development of reliable and handy detection tools for ClO- and Ga3+ in the environment and food is crucial. In this study, a ratiometric fluorescent probe was prepared based on benzothiazolaldehyde and pyridine-2-carboxylic acid hydrazide, which exhibited exceptional performance characteristics for the selective detection of ClO- and Ga3+. These features include high specificity, low detection limits (0.28 µM for ClO-, 0.13 µM for Ga3+), mild pH conditions (pH 4-11 for ClO-, pH 6-11 for Ga3+), fast response time (within 30 s), as well as versatile applicability across different matrices such as water, soil, food, and plant samples. Additionally, this probe can be used with a smartphone color recognition app. The probe offers a convenient and effective tool for the detection of ClO- and Ga3+, demonstrating its potential application value in environmental monitoring and food safety.
Asunto(s)
Colorantes Fluorescentes , Galio , Ácido Hipocloroso , Espectrometría de Fluorescencia , Ácido Hipocloroso/análisis , Galio/química , Colorantes Fluorescentes/química , Espectrometría de Fluorescencia/métodos , Límite de Detección , Análisis de los Alimentos/métodos , Contaminación de Alimentos/análisis , Monitoreo del Ambiente/métodos , Concentración de Iones de HidrógenoRESUMEN
The exclusion mechanism of food contaminants such as bisphenol A (BPA), Flavonoids (FLA), and Goitrin (GOI) onto the novel gallium-metal organic framework (MOF) and functionalized MOF with oxalamide group (MOF-OX) is evaluated by utilizing molecular dynamics (MD) and Metadynamics simulations. The atoms in molecules (AIM) analysis detected different types of atomic interactions between contaminant molecules and substrates. To assess this procedure, a range of descriptors including interaction energies, root mean square displacement, radial distribution function (RDF), density, hydrogen bond count (HB), and contact numbers are examined across the simulation trajectories. The most important elements in the stability of the systems under examination are found to be stacking π-π and HB interactions. It was confirmed by a significant value of total interaction energy for BPA/MOF-OX (- 338.21 kJ mol-1) and BPA/MOF (- 389.95 kJ mol-1) complexes. Evaluation of interaction energies reveals that L-J interaction plays an essential role in the adsorption of food contaminants on the substrates. The free energy values for the stability systems of BPA/MOF and BPA/MOF-OX complexes at their global minima reached about BPA/MOF = - 254.29 kJ mol-1 and BPA/MOF-OX = - 187.62 kJ mol-1, respectively. Nevertheless, this work provides a new strategy for the preparation of a new hierarchical tree-dimensional of the Ga-MOF hybrid material for the adsorption and exclusion of food contaminates and their effect on human health.
Asunto(s)
Contaminación de Alimentos , Galio , Estructuras Metalorgánicas , Simulación de Dinámica Molecular , Estructuras Metalorgánicas/química , Galio/química , Contaminación de Alimentos/análisis , Fenoles/química , Fenoles/análisis , Compuestos de Bencidrilo/química , Compuestos de Bencidrilo/análisis , Enlace de Hidrógeno , Adsorción , Flavonoides/química , Flavonoides/análisisRESUMEN
In order to implement the fifth generation (5G) communication system for a large number of users, the governments of many countries nominated the low 5G frequency band between 3.3 and 4.3 GHz. This paper proposes a wideband RFPA by designing the input matching network (MN) and output MN of the device using the simplified real frequency technique (SRFT) and the harmonic tuning network. The load-pull and source-pull is applied at multiple points for 100 MHz intervals over the bandwidth to obtain the optimum impedances at the output and input of the 10W Gallium Nitride (GaN) Cree CGH40010F device. To verify the design, the RFPA is simulated, and the performance is measured between 3.3 and 4.3 GHz. According to experimental findings, the measured drain efficiency (DE) throughout the whole bandwidth ranged from 57.5 to 67.5% at the output power of 40 dBm. Moreover, at the 1 dB compression point between 39.2 and 42.2 dBm output power, the drain efficiency (DE) achieves a high value of 81.2% with an output power of 42.2 dBm at a frequency of 3.3 GHz. The RFPA can obtain a maximum gain of 12.4 dB at 3.5 GHz. The linearity of the RFPA with a two-tone signal is measured and the value is less than -22 dBc all over the band.
Asunto(s)
Galio , Galio/química , Diseño de Equipo , Amplificadores Electrónicos , Tecnología Inalámbrica/instrumentaciónRESUMEN
MgGa alloys are considered highly potential biodegradable materials, owing to its good mechanical properties and appropriate corrosion resistance. However, it is still far from application due to the lack of biological evaluation. In the present study, biocompatibility, osteogenesis and antibacterial activity of extruded Mg-xGa (x = 1 and 5 wt%) alloys were investigated by in vitro cell culture experiments and in vivo implantation. The cell adhesion and proliferation of osteoblast precursor cells (MC3T3-E1) showed the excellent cytocompatibility of Mg-1Ga and poor cytocompatibility of Mg-5Ga. The osteogenic activity was evaluated and revealed that Ga3+ in the Mg-1Ga extract had the ability to enhance osteogenic differentiation through the facilitation of its early stages. In vivo studies in a rat femoral condyle model revealed that both Mg-1Ga and Mg-5Ga significantly promoted new bone formation without causing any adverse effects. Mg-5Ga exhibited a much higher corrosion rate in vivo than Mg-1Ga. Its osteogenic activity was better due to the rapid release of Mg2+ and Ga3+, but this caused premature structural integrity loss. Mg-1Ga and Mg-5Ga released Ga3+ to inhibit E. coli and S. aureus, with antibacterial rate increasing with Ga content. Our studies demonstrate that Mg-Ga alloys have the potential to be used as osteogenic and antibacterial implant materials. STATEMENT OF SIGNIFICANCE: This study evaluates the biocompatibility, osteogenesis, and antibacterial activity of Mg-Ga alloys, which are promising biodegradable materials for medical applications. The study finds that Mg-1Ga exhibits excellent cytocompatibility and promotes osteogenic differentiation, facilitating the early stages of osteoblast precursor cell development. In vivo studies in a rat femoral condyle model reveal that Mg-1Ga and Mg-5Ga significantly promote new bone formation without causing any adverse effects. The antibacterial activity of both alloys is evaluated against E. coli and S. aureus, with the inhibition rate increasing with Ga content. These findings suggest that Mg-Ga alloys have the potential to serve as osteogenic and antibacterial implant materials, providing significant insights into the development of novel biomedical implants.
Asunto(s)
Aleaciones , Antibacterianos , Galio , Magnesio , Osteogénesis , Animales , Osteogénesis/efectos de los fármacos , Antibacterianos/farmacología , Antibacterianos/química , Aleaciones/farmacología , Aleaciones/química , Ratones , Galio/química , Galio/farmacología , Magnesio/farmacología , Magnesio/química , Ratas , Ratas Sprague-Dawley , Staphylococcus aureus/efectos de los fármacos , Escherichia coli/efectos de los fármacos , Masculino , Ensayo de Materiales , Línea Celular , Corrosión , Proliferación Celular/efectos de los fármacosRESUMEN
Staphylococcus aureus (S. aureus) is one of the most common wound pathogens with increased resistance towards currently available antimicrobials. S. aureus biofilms lead to increase wound chronicity and delayed healing. Chitosan-dextran hydrogel (Chitogel) loaded with the hydroxypyridinone-derived iron chelator Deferiprone (Def) and the heme analogue Gallium-Protoporphyrin (GaPP) have previously been shown to have antimicrobial effects in clinical sinusitis. In this study, the efficacy of Chitogel loaded with Def, GaPP and a combination of Def and GaPP, were investigated in an S. aureus biofilm infected wound murine model over 10 days of treatment. Bacterial wound burden was monitored daily showing a significant decrease in bacterial bioburden on days 6 and 8 when treated with Def-GaPP Chitogel (log10 1.0 and 1.2 reduction vs control, respectively). The current study demonstrates that the combination of Def-GaPP delivered in a Chitogel in vivo is not only effective in reducing S. aureus biofilm infection, but also improves cutaneous healing via effects on reduced inflammation, promotion of anti-inflammatory macrophage phenotype and marked early collagen deposition in the wound bed. This delivery platform presents a promising alternative non-toxic, antibacterial, wound-promoting treatment as a novel approach for the management of S. aureus wound infections that warrants further clinical investigation.
Asunto(s)
Biopelículas , Quitosano , Deferiprona , Galio , Protoporfirinas , Staphylococcus aureus , Cicatrización de Heridas , Animales , Staphylococcus aureus/efectos de los fármacos , Ratones , Quitosano/química , Quitosano/farmacología , Biopelículas/efectos de los fármacos , Deferiprona/farmacología , Deferiprona/química , Deferiprona/uso terapéutico , Galio/química , Galio/farmacología , Cicatrización de Heridas/efectos de los fármacos , Protoporfirinas/farmacología , Protoporfirinas/química , Infecciones Estafilocócicas/tratamiento farmacológico , Infecciones Estafilocócicas/microbiología , Antibacterianos/farmacología , Antibacterianos/química , Hidrogeles/química , Infección de Heridas/tratamiento farmacológico , Infección de Heridas/microbiología , Piel/microbiología , Piel/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Antiinfecciosos/farmacología , Antiinfecciosos/química , Piridonas/química , Piridonas/farmacología , Piridonas/uso terapéuticoRESUMEN
Homocysteine (Hcy) and C-reactive protein (CRP) are critical biomarkers for numerous chronic diseases, with cardiovascular disease (CVD) being the most prevalent. The ability to simultaneously detect both biomarkers in point-of-care settings is in high demand for CVD early diagnosis and prevention. Herein, we prepared the eutectic gallium indium (EGaIn) nanoparticles decorated with p-phenylenediamine (PPD) on the surface to facilitate the subsequent attachment of gold nanoparticles (AuNPs) to achieve EGaIn-PPD@Au, which was modified on the screen-printed electrochemical paper-based analytical devices (ePADs). Aptamers that are specific to Hcy and CRP were then immobilized on the EGaIn-PPD@Au surface to achieve the sensing interface on ePADs. The presence of EGaIn-PPD@Au significantly enhanced the electrical conductivity, leading to amplified electrochemical signals. This aptasensor demonstrated high specificity, capable of detecting Hcy in a range of 1-50 µM with a detection limit of 0.22 µM, and the detection range for CRP was 1-100 ng/mL with a detection limit of 0.039 ng/mL. The aptasensor also effectively detected Hcy and CRP in clinical saliva samples, yielding an area under the curve (AUC) of about 0.80 when the individual biomarker was considered and 0.93 when both biomarkers were taken into account. The positive correlation observed between salivary and blood concentrations of Hcy and CRP, coupled with their association with cardiovascular disease (CVD), suggested the potential of this methodology as a noninvasive point-of-care strategy for the early diagnosis of CVD.
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Proteína C-Reactiva , Enfermedades Cardiovasculares , Diagnóstico Precoz , Galio , Oro , Homocisteína , Indio , Nanopartículas del Metal , Saliva , Proteína C-Reactiva/análisis , Humanos , Homocisteína/análisis , Homocisteína/sangre , Enfermedades Cardiovasculares/diagnóstico , Saliva/química , Oro/química , Nanopartículas del Metal/química , Indio/química , Galio/química , Técnicas Electroquímicas/métodos , Aptámeros de Nucleótidos/química , Límite de Detección , Técnicas Biosensibles/métodos , Papel , Fenilendiaminas/química , Biomarcadores/sangre , Biomarcadores/análisisRESUMEN
The binding ability of 8-hydroxyquinoline-2-carboxylic acid (8-HQA) towards Ga3+ has been investigated by ISEH+ (Ion Selective Electrode, glass electrode) potentiometric and UV/Vis spectrophotometric titrations in KCl(aq) at I = 0.2 mol dm-3 and at T = 298.15 K. Further experiments were also performed adopting both the metal (with Fe3+ as competing cation) and ligand-competition approaches (with EDTA as competing ligand). Results gave evidence of the formation of the [Ga(8-HQA)]+, [Ga(8-HQA)(OH)], [Ga(8-HQA)(OH)2]- and [Ga(8-HQA)2]- species, the latter being so far the most stable, as also confirmed by ESI-MS analysis. Experiments were also designed to determine the stability constants of the [Ga(EDTA)]- and [Ga(EDTA)(OH)]2- in the above conditions. Due to the relevance of Ga3+ hydrolysis in aqueous systems, literature data on this topic were collected and critically analyzed, providing equations for the calculation of mononuclear Ga3+ hydrolysis constants at T = 298.15 K, in different ionic media, in the ionic strength range 0 < I / mol dm-3 ≤ 1.0. The synthesis and characterization (by ElectroSpray Ionization - Mass Spectrometry (ESI-MS), Attenuated Total Reflectance - Fourier-Transform Infrared Spectroscopy (ATR-FTIR) and ThermoGravimetric Analysis (TGA)) of Ga3+/8-HQA complexes were also performed, identifying [Ga(8-HQA)2]- as the main isolated species, even in the solid state. Finally, the potential effects of 8-HQA and Ga3+/8-HQA complex towards human microbiota exposed to ionizing radiation were evaluated (namely Actinomyces viscosus, Streptococcus mutans, Streptococcus sobrinus, Pseudomonas putida, Pseudomonas fluorescens and Escherichia coli), as well as their anti-proliferative and anti-inflammatory properties. A radioprotective effect of Ga3+/8-HQA complex was observed on Actinomyces viscosus, while showing a potential radiosensitizing effect against Streptococcus mutans and Streptococcus sobrinus. No cytotoxicity on RAW264.7 murine macrophage cells was observed, neither for the free ligand or Ga3+/8-HQA complex. Nevertheless, Ga3+/8-HQA complex highlighted potential anti-inflammatory properties.
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Complejos de Coordinación , Galio , Oxiquinolina , Oxiquinolina/química , Oxiquinolina/farmacología , Galio/química , Complejos de Coordinación/química , Complejos de Coordinación/farmacología , Animales , Ratones , Humanos , Antibacterianos/farmacología , Antibacterianos/químicaRESUMEN
The effect of 60Co gamma irradiation on gallium oxide and titanium oxide (Ga2O3-TiO2) nanocomposites are investigated in the present study. The Ga2O3-TiO2 nanocomposite was synthesized by hydrothermal method at 120°C. The precursors for the synthesis consist of gallium nitrate anhydrous and titanium trichloride along with sodium hydroxide to achieve the pH of 9. The synthesized Ga2O3-TiO2 was subjected to 60Co gamma irradiation for different doses such as 25, 50 and 75 kGy. The morphological, optical and microstructural characteristics were studied using scanning electron microscopy, UV-Visible spectroscopy, X-ray diffraction and Fourier transform infrared spectroscopy, respectively. The results shows that the gamma irradiation induces significant changes in the Ga2O3-TiO2 microstructure and there is increase in the grain size and bandgap of the nanocomposites.
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Radioisótopos de Cobalto , Galio , Rayos gamma , Nanocompuestos , Titanio , Titanio/química , Nanocompuestos/química , Nanocompuestos/efectos de la radiación , Radioisótopos de Cobalto/química , Galio/química , Difracción de Rayos X , Espectroscopía Infrarroja por Transformada de Fourier , Microscopía Electrónica de RastreoRESUMEN
Quantitative contrast-enhanced breast computed tomography (CT) has the potential to improve the diagnosis and management of breast cancer. Traditional CT methods using energy-integrated detectors and dual-exposure images with different incident spectra for material discrimination can increase patient radiation dose and be susceptible to motion artifacts and spectral resolution loss. Photon Counting Detectors (PCDs) offer a promising alternative approach, enabling acquisition of multiple energy levels in a single exposure and potentially better energy resolution. Gallium arsenide (GaAs) is particularly promising for breast PCD-CT due to its high quantum efficiency and reduction of fluorescence x-rays escaping the pixel within the breast imaging energy range. In this study, the spectral performance of a GaAs PCD for quantitative iodine contrast-enhanced breast CT was evaluated. A GaAs detector with a pixel size of 100µm, a thickness of 500µm was simulated. Simulations were performed using cylindrical phantoms of varying diameters (10 cm, 12 cm, and 16 cm) with different concentrations and locations of iodine inserts, using incident spectra of 50, 55, and 60 kVp with 2 mm of added aluminum filtration and and a mean glandular dose of 10 mGy. We accounted for the effects of beam hardening and energy detector response using TIGRE CT open-source software and the publicly available Photon Counting Toolkit (PcTK). Material-specific images of the breast phantom were produced using both projection and image-based material decomposition methods, and iodine component images were used to estimate iodine intake. Accuracy and precision of the proposed methods for estimating iodine concentration in breast CT images were assessed for different material decomposition methods, incident spectra, and breast phantom thicknesses. The results showed that both the beam hardening effect and imperfection in the detector response had a significant impact on performance in terms of Root Mean Squared Error (RMSE), precision, and accuracy of estimating iodine intake in the breast. Furthermore, the study demonstrated the effectiveness of both material decomposition methods in making accurate and precise iodine concentration predictions using a GaAs-based photon counting breast CT system, with better performance when applying the projection-based material decomposition approach. The study highlights the potential of GaAs-based photon counting breast CT systems as viable alternatives to traditional imaging methods in terms of material decomposition and iodine concentration estimation, and proposes phantoms and figures of merit to assess their performance.
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Arsenicales , Neoplasias de la Mama , Mama , Medios de Contraste , Galio , Yodo , Mamografía , Fantasmas de Imagen , Fotones , Tomografía Computarizada por Rayos X , Galio/química , Humanos , Femenino , Tomografía Computarizada por Rayos X/métodos , Medios de Contraste/química , Mamografía/métodos , Neoplasias de la Mama/diagnóstico por imagen , Mama/diagnóstico por imagen , Simulación por Computador , Método de Montecarlo , Procesamiento de Imagen Asistido por Computador/métodos , Dosis de RadiaciónRESUMEN
In this study, we address the challenge of developing highly conductive hydrogels with enhanced stretchability for use in wearable sensors, which are critical for the precise detection of human motion and subtle physiological strains. Our novel approach utilizes amylopectin, a biopolymer, for the uniform integration of liquid metal gallium into the hydrogel matrix. This integration results in a conductive hydrogel characterized by remarkable elasticity (up to 7100 % extensibility) and superior electrical conductance (Gauge Factor = 31.4), coupled with a minimal detection limit of less than 0.1 % and exceptional durability over 5000 cycles. The hydrogel demonstrates significant antibacterial activity, inhibiting microbial growth in moist environments, thus enhancing its applicability in medical settings. Employing a synthesis process that involves ambient condition polymerization of acrylic acid, facilitated by a hydrophobic associative framework, this hydrogel stands out for its rapid gelation and robust mechanical properties. The potential applications of this hydrogel extend beyond wearable sensors, promising advancements in human-computer interaction through technologies like wireless actuation of robotic systems. This study not only introduces a viable material for current wearable technologies but also sets a foundation for future innovations in bio-compatible sensors and interactive devices.