Selective detection of food contaminants using engineered gallium-organic frameworks with MD and metadynamics simulations.

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.

Erythrocyte-Mimicking Nanovesicle Targeting Porphyromonas gingivalis for Periodontitis.

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.

Probiotics functionalized with a gallium-polyphenol network modulate the intratumor microbiota and promote anti-tumor immune responses in pancreatic cancer.

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.

Multifunctional long afterglow nanoparticles with enhanced photothermal effects for in vivo imaging and tumor-targeting therapy.

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.

A ratiometric fluorescent probe for selective detection of hypochlorite (ClO-) and gallium (III) (Ga3+) ions in environmental and food samples.

Hypochlorite (ClO-) and gallium (Ⅲ) 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.

A Two-Pronged Nanostrategy of Iron Metabolism Disruption to Synergize Tumor Therapy by Triggering the Paraptosis-Apoptosis Hybrid Pathway.

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.

3.3-4.3 GHz efficient continuous class-F gallium nitride power amplifier based on simplified real frequency technique and harmonic tuning.

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.

Implementation of Three Gallium-Based Complexes in the "Trojan Horse" Antibacterial Strategy against A. baumannii: A DFT Approach.

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.

Solution studies, synthesis and antibacterial activity of Ga(III) complexes with bis-kojate derivatives.

Given the recognized major problem of microbial drug resistance for human health, new metal-based drugs have been currently explored for their antimicrobial properties, including gallium-based compounds as potential metallophores that could perturb Fe's interactions with proteins. Herein we have designed and synthesized two bis-kojate ligands (named L4 and L6) and studied their Ga(III) complexes for their physico-chemical and biological properties. In particular a detailed study of their complexation properties in aqueous solution, showed equilibrium models with formation of quite stable dinuclear 2:3 metal:ligand complexes, though with different stability. Solid state complexes were also prepared and characterized and complementary DFT studies indicated that [Ga2(L4)3] complex, with higher stability, seems to adopt a three-ligand bridging conformation, while that for L6 adopt a one ligand bridging conformation. Preliminary investigation of the antibacterial activity of these gallium complexes showed antipseudomonal activity, which appeared higher for the complex with L4, a feature of potential interest for the scientific community.

Quantitative evaluation of 67Ga-citrate scintigraphy in the management of nephritis.

In 67Ga-citrate scintigraphy (Ga-S), visual assessment is used by evaluating renal-uptake comparison with liver and spine and is simple and objective. We adopted the standardized uptake value (SUV) for 67Ga-citrate and proposed two quantitative indices, active nephritis volume (ANV) and total nephritis uptake (TNU). This study clarified the utility of new Ga-S-based quantitative indices in nephritis management. Before SUV measurement, the Becquerel calibration factor of 67Ga-citrate was obtained using a phantom experiment. Seventy patients who underwent SPECT/CT imaging were studied. SUV, ANV, and TNU were calculated using a quantitative analysis software for bone SPECT. SUVmean, ANV, and TNU were analyzed using the (1) threshold method (set 40%) and constant-value method for (2) vertebral SUVmax, and (3) vertebral SUVmean. ROC analysis was used to evaluate SUV, ANV, and TNU diagnostic abilities to distinguish nephritis presence and absence as well as interstitial nephritis (IN) and non-IN. The area under the curve (AUC) for nephritis presence or absence had a good value (0.80) for SUVmean (1), ANV (3), and TNU (3). The AUC for differentiation between IN and non-IN groups had a good value (0.80) for SUVmean (1). Thus, the new Ga-S-based quantitative indices were useful to evaluate nephritis and distinguish IN and non-IN.

Melatonin-loaded mesoporous zinc- and gallium-doped hydroxyapatite nanoparticles to control infection and bone repair.

Effective treatment of infected bone defects resulting from multi-drug resistant bacteria (MDR) has emerged as a significant clinical challenge, highlighting the pressing demand for potent antibacterial bone graft substitutes. Mesoporous nanoparticles have been introduced as a promising class of biomaterials offering significant properties for treating bone infections. Herein, we synthesize antibacterial mesoporous hydroxyapatite substituted with zinc and gallium (Zn-Ga:mHA) nanoparticles using a facile sol-gel method. The resulting mesoporous nanoparticles are applied for the controlled release of melatonin (Mel). Zn-Ga:mHA nanoparticles with an average particle size of 36 ± 3 nm and pore size of 10.6 ± 0.4 nm reveal a Mel loading efficiency of 58 ± 1%. Results show that 50% of Mel is released within 20 h and its long-term release is recorded up to 50 h. The Zn-Ga:mHA nanoparticles exhibit highly effective antibacterial performance as reflected by a 19 ± 1% and 8 ± 2% viability reduction in Escherichia coli and Staphylococcus bacteria, respectively. Noticeably, Mel-loaded Zn-Ga:mHA nanoparticles are also cytocompatible and stimulate in vitro osteogenic differentiation of human mesenchymal stem cells (hMSCs) without any osteoinductive factor. In vivo studies in a rabbit skull also show significant regeneration of bone during 14 days. In summary, Mel-loaded Zn-Ga:mHA nanoparticles provide great potential as an antibacterial and osteogenic component in bone substitutes like hydrogels, scaffolds, and coatings.

Deferiprone and Gallium-Protoporphyrin Chitogel as an antimicrobial treatment: Preclinical studies demonstrating antimicrobial activity for S. aureus infected cutaneous wounds.

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.

EGaIn-Modified ePADs for Simultaneous Detection of Homocysteine and C-Reactive Protein in Saliva toward Early Diagnosis of Cardiovascular Disease.

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.

Effect of 60Co gamma irradiation on hydrothermally synthesized Ga2O3-Tio2 nanocomposites.

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.

Evaluating spectral performance for quantitative contrast-enhanced breast CT with a GaAs based photon counting detector: a simulation approach.

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.

Highly stretchable, self-healing, antibacterial, conductive, and amylopectin-enhanced hydrogels with gallium droplets loading as strain sensors.

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.

Orally administrated liquid metal agents for inflammation-targeted alleviation of inflammatory bowel diseases.

Rapid drug clearance and off-target effects of therapeutic drugs can induce low bioavailability and systemic side effects and gravely restrict the therapeutic effects of inflammatory bowel diseases (IBDs). Here, we propose an amplifying targeting strategy based on orally administered gallium (Ga)-based liquid metal (LM) nano-agents to efficiently eliminate reactive oxygen and nitrogen species (RONS) and modulate the dysregulated microbiome for remission of IBDs. Taking advantage of the favorable adhesive activity and coordination ability of polyphenol structure, epigallocatechin gallate (EGCG) is applied to encapsulate LM to construct the formulations (LM-EGCG). After adhering to the inflamed tissue, EGCG not only eliminates RONS but also captures the dissociated Ga to form EGCG-Ga complexes for enhancive accumulation. The detained composites protect the intestinal barrier and modulate gut microbiota for restoring the disordered enteral microenvironment, thereby relieving IBDs. Unexpectedly, LM-EGCG markedly decreases the Escherichia_Shigella populations while augmenting the abundance of Akkermansia and Bifidobacterium, resulting in favorable therapeutic effects against the dextran sulfate sodium-induced colitis.

Dual-functional gallium/chitosan/silk/umbilical cord mesenchymal stem cell exosome sponge scaffold for diabetic wound by angiogenesis and antibacteria.

The treatment of diabetic wounds possessed significant challenges in clinical practice, which was accompanied with continuous infection, inflammation, and limited angiogenesis. Current wound dressings used for diabetic wound healing struggle to address these issues simultaneously. Therefore, Ga3+ was added to the chitosan/silk solution to confer potent antibacterial properties. Subsequently, umbilical cord mesenchymal stem cell exosomes (UCSC-Exo) were integrated into the gallium/chitosan/silk solution to enhance its angiogenesis-inducing activity. The mixture was lyophilized to prepare gallium/chitosan/silk/exosome sponge scaffolds (Ga/CSSF-Exo sponge scaffolds). The experiments of In vitro and in vivo demonstrated that Ga/CSSF-Exo sponge scaffolds exhibited sustained release of Ga3+ and bioactive exosomes, which effectively exerted continuous antibacterial effects and promoted angiogenesis. In diabetic rat wound models, Ga/CSSF-Exo sponge scaffolds facilitated angiogenesis, suppressed bacterial growth and inflammation, as well as promoted collagen deposition and re-epithelialization of wounds. Collectively, our findings suggested that Ga/CSSF-Exo held excellent potential for diabetic wound healing.

Effect of gallium nitrate on the antibacterial activity of vancomycin in methicillin-sensitive and resistant Staphylococcus aureus.

The extension of multidrug-resistant strains of Staphylococcus aureus (S. aureus) is one of the main health challenges in the world, which requires serious solutions to deal with it. Combination therapies using conventional antibiotics and new antibacterial compounds that target different bacterial pathways are effective methods against resistant bacterial infections. Gallium is an iron-like metal that competes with iron for uptake into bacteria and has the potential to disrupt iron-dependent vital processes in bacteria. In this study, we explored the antibacterial effects of gallium nitrate (Ga(NO3)3) and vancomycin alone and in combination with each other on methicillin-sensitive S. aureus (MSSA) and methicillin-resistant S. aureus (MRSA) using microdilution assay and checkerboard test, respectively. Then, their effect on the formation and destruction of biofilms was investigated. Finally, the amount of ROS production in the presence of these two compounds in bacteria was evaluated. The results indicated that the vancomycin/ Ga(NO3)3 combination reduced the MIC of vancomycin in the MRSA strain and had an additive effect on it. Vancomycin plus Ga(NO3)3 reduced the formation of biofilms and increased the destruction of biofilms formed in both strains, especially in the MRSA strain. ROS production was also higher in the combination of vancomycin with Ga(NO3)3 compared to vancomycin alone, especially in MRSA. Therefore, our results showed that Ga(NO3)3 enhances the antibacterial activity of vancomycin and this combination therapy can be considered as a new strategy for the treatment of MRSA infections.

In vitroassessment of a gallium-doped glass polyalkenoate cement: chemotherapeutic potential, cytotoxicity and osteogenic effects.

Metastatic bone lesions are often osteolytic, which causes advanced-stage cancer sufferers to experience severe pain and an increased risk of developing a pathological fracture. Gallium (Ga) ion possesses antineoplastic and anti-bone resorption properties, suggesting the potential for its local administration to impede the growth of metastatic bone lesions. This study investigated the chemotherapeutic potential, cytotoxicity, and osteogenic effects of a Ga-doped glass polyalkenoate cement (GPC) (C-TA2) compared to its non-gallium (C-TA0) counterpart. Ion release profiles revealed a biphasic pattern characterized by an initial burst followed by a gradually declining release of ions. C-TA2 continued to release Ga steadily throughout the experimentation period (7 d) and exhibited prolonged zinc (Zn) release compared to C-TA0. Interestingly, the Zn release from both GPCs appeared to cause a chemotherapeutic effect against H1092 lung cancer cellsin vitro, with the prolonged Zn release from C-TA2 extending this effect. Unfortunately, both GPCs enhanced the viability of HCC2218 breast cancer cells, suggesting that the chemotherapeutic effects of Zn could be tied to cellular differences in preferred Zn concentrations. The utilization of SAOS-2 and MC3T3 cell lines as bone cell models yielded conflicting results, with the substantial decline in MC3T3 viability closely associated with silicon (Si) release, indicating cellular variations in Si toxicity. Despite this ambiguity, both GPCs exhibited harmful effects on the osteogenesis of primary rat osteoblasts, raising concerns about excessive burst Zn release. While Ga/Zn-doped GPCs hold promise for treating metastatic bone lesions caused by lung cancers, further optimization is required to mitigate cytotoxicity on healthy bone.