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1.
Sci Adv ; 10(28): eadn1745, 2024 Jul 12.
Article in English | MEDLINE | ID: mdl-38996026

ABSTRACT

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.


Subject(s)
Gastrointestinal Microbiome , Inflammatory Bowel Diseases , Animals , Inflammatory Bowel Diseases/drug therapy , Administration, Oral , Gastrointestinal Microbiome/drug effects , Mice , Catechin/analogs & derivatives , Catechin/chemistry , Catechin/administration & dosage , Catechin/pharmacology , Gallium/chemistry , Gallium/pharmacology , Disease Models, Animal , Inflammation/drug therapy , Reactive Oxygen Species/metabolism , Colitis/drug therapy , Humans , Reactive Nitrogen Species/metabolism
2.
Sci Rep ; 14(1): 16313, 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-39009630

ABSTRACT

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.


Subject(s)
Gallium Radioisotopes , Gallium , Humans , Male , Female , Middle Aged , Aged , Adult , Nephritis/diagnostic imaging , Citrates , ROC Curve , Aged, 80 and over , Radiopharmaceuticals , Single Photon Emission Computed Tomography Computed Tomography/methods
3.
Radiat Prot Dosimetry ; 200(11-12): 1173-1177, 2024 Jul 17.
Article in English | MEDLINE | ID: mdl-39016480

ABSTRACT

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.


Subject(s)
Cobalt Radioisotopes , Gallium , Gamma Rays , Nanocomposites , Titanium , Titanium/chemistry , Nanocomposites/chemistry , Nanocomposites/radiation effects , Cobalt Radioisotopes/chemistry , Gallium/chemistry , X-Ray Diffraction , Spectroscopy, Fourier Transform Infrared , Microscopy, Electron, Scanning
4.
Biomed Phys Eng Express ; 10(5)2024 Jul 17.
Article in English | MEDLINE | ID: mdl-38968931

ABSTRACT

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.


Subject(s)
Arsenicals , Breast Neoplasms , Breast , Contrast Media , Gallium , Iodine , Mammography , Phantoms, Imaging , Photons , Tomography, X-Ray Computed , Gallium/chemistry , Humans , Female , Tomography, X-Ray Computed/methods , Contrast Media/chemistry , Mammography/methods , Breast Neoplasms/diagnostic imaging , Breast/diagnostic imaging , Computer Simulation , Monte Carlo Method , Image Processing, Computer-Assisted/methods , Radiation Dosage
5.
Nanoscale ; 16(24): 11669-11678, 2024 Jun 20.
Article in English | MEDLINE | ID: mdl-38855849

ABSTRACT

Implant infections are severe complications in clinical treatment, which often accompany the formation of bacterial biofilms with high antibiotic resistance. Sonodynamic therapy (SDT) is an antibiotic-free method that can generate reactive oxygen species (ROS) to kill bacteria under ultrasound (US) treatment. However, the extracellular polymeric substances (EPS) barrier of bacterial biofilms and the hypoxic microenvironment significantly limit the antibiofilm activity of SDT. In this study, lipid-shelled perfluoropentane (PFP) nanodroplets loaded with gallium protoporphyrin IX (GaPPIX) and oxygen (O2) (LPGO NDs) were developed for the treatment of implant infections. Under US stimulation, LPGO NDs undergo the cavitation effect and disrupt the biofilm structure like bombs due to liquid-gas phase transition. Meanwhile, the LPGO NDs release O2 and GaPPIX upon US stimulation. The released O2 can alleviate the hypoxic microenvironment in the biofilm and enhance the ROS formation by GaPPIX for enhanced bacterial killing. In vivo experimental results demonstrate that the LPGO NDs can efficiently treat implant infections of methicillin-resistant Staphylococcus aureus (MRSA) in a mouse model by disrupting the biofilm structure, alleviating hypoxia, and enhancing bacterial killing by SDT. Therefore, this work provides a new multifunctional sonosensitizer to overcome the limitations of SDT for treating implant infections.


Subject(s)
Biofilms , Fluorocarbons , Gallium , Methicillin-Resistant Staphylococcus aureus , Oxygen , Protoporphyrins , Staphylococcal Infections , Ultrasonic Therapy , Animals , Fluorocarbons/chemistry , Fluorocarbons/pharmacology , Mice , Gallium/chemistry , Gallium/pharmacology , Protoporphyrins/chemistry , Protoporphyrins/pharmacology , Methicillin-Resistant Staphylococcus aureus/drug effects , Biofilms/drug effects , Oxygen/chemistry , Staphylococcal Infections/drug therapy , Reactive Oxygen Species/metabolism , Nanoparticles/chemistry , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Mice, Inbred BALB C , Female , Pentanes
6.
Phys Chem Chem Phys ; 26(25): 17817-17829, 2024 Jun 26.
Article in English | MEDLINE | ID: mdl-38884203

ABSTRACT

There is currently a great deal of interest in realizing localized surface plasmon resonances (LSPRs) in two distinct windows in the near-infrared (NIR) spectrum for in vivo biosensing and medical applications, the biological window (BW) I and II (BW I, 700-900 nm; BW II, 1000-1700 nm). This study aims to demonstrate that LSPRs of Ga-doped ZnO (GZO) core-silver (Ag) shell structures exhibit promising features for biological applications in the NIR BW I and II. Here, we study three different shapes for nanoshells: the core-shell nanosphere, nanorod, and nanodisk. In the calculation of the optical response of these nanoshells, an effective medium approach is first used to reduce the dielectric function of a nanoshell to that of an equivalent homogenous NP with an effective dielectric function. Then, the LSPR spectra of nanoshells are calculated using the modified long-wavelength approximation (MLWA), which corrects the polarizability of the equivalent NP as obtained by Gans theory. Through numerical investigations, we examine the impacts of the core and shell sizes of the proposed nanoshells as well as the medium refractive index on the position and line width of the plasmon resonance peaks. It is shown that the plasmon resonances of the three proposed nanoshells exhibit astonishing resonance tunability in the NIR region by varying their geometrical parameters. Specifically, the improved spectrum characteristics and tunability of its plasmon resonances make the GZO-Ag nanosphere a more viable platform for NIR applications than the spherical metal colloid. Furthermore, we demonstrate that the sensitivity and figure of merit (FOM) of the plasmon resonances may be significantly increased by using GZO-Ag nanorods and nanodisks in place of GZO-Ag nanospheres. It is found that the optical properties of the transverse plasmon resonance of the GZO-Ag nanodisk are superior to all plasmon resonances produced by the GZO-Ag nanorods and GZO-Ag nanospheres in terms of sensitivity and FOM. The FOM of the transverse plasmon mode of the GZO-Ag nanodisk is almost two orders of magnitude higher than that of the longitudinal and transverse plasmon modes of the GZO-Ag nanorod in BW I and BW II. And it is 1.5 and 2 times higher than the plasmon resonance FOM of GZO-Ag nanospheres in BW I and BW II, respectively.


Subject(s)
Biosensing Techniques , Nanospheres , Nanotubes , Silver , Surface Plasmon Resonance , Zinc Oxide , Silver/chemistry , Nanotubes/chemistry , Zinc Oxide/chemistry , Biosensing Techniques/methods , Nanospheres/chemistry , Gallium/chemistry , Infrared Rays
7.
Anal Methods ; 16(26): 4381-4386, 2024 Jul 04.
Article in English | MEDLINE | ID: mdl-38896043

ABSTRACT

The abundant bio-markers in saliva provide a new option for non-invasive testing. However, due to the presence of impurities in the saliva background, most of the existing saliva testing methods rely on pre-processing, which limits the application of saliva testing as a convenient means of testing in daily life. Herein, a disposable-gate AlGaN/GaN high electron mobility transistor (HEMT) biosensor integrated with a micro-sieve was introduced to solve the problem of signal interference caused by charged impurities in saliva for HEMT based biosensors, where the micro-sieve was utilized as a pre-treatment unit to remove large particles of impurities from saliva through the size effect and thus greatly improving the accuracy of detection. The experimental results showed that the HEMT based biosensor has excellent linearity (R2 = 0.9977) and a high sensitivity of 6.552 µA dec-1 for urea sensing from 1 fM to 100 mM in 0.1× PBS solution. When it comes to artificial saliva detection, compared to the HEMT sensor without the micro-sieve (sensitivity = 3.07432 µA dec-1), the sensitivity of the HEMT sensor integrated with the micro-sieve showed almost no change. Moreover, to verify that urea can be detected in actual saliva, urea is sensed directly in human saliva. The addition of the microsieve module provides a new way for biosensors to detect specific markers in saliva in real time, and the designed HEMT biosensor with the microsieve function has a wide range of application potential in rapid saliva detection.


Subject(s)
Biosensing Techniques , Gallium , Saliva , Transistors, Electronic , Urea , Gallium/chemistry , Gallium/analysis , Biosensing Techniques/instrumentation , Biosensing Techniques/methods , Urea/analysis , Urea/chemistry , Saliva/chemistry , Humans , Aluminum Compounds/chemistry , Aluminum Compounds/analysis , Limit of Detection , Electrochemical Techniques/instrumentation , Electrochemical Techniques/methods , Equipment Design
8.
ACS Biomater Sci Eng ; 10(7): 4452-4462, 2024 Jul 08.
Article in English | MEDLINE | ID: mdl-38875708

ABSTRACT

Mg-based biodegradable metallic implants are gaining increased attraction for applications in orthopedics and dentistry. However, their current applications are hampered by their high rate of corrosion, degradation, and rapid release of ions and gas bubbles into the physiological medium. The aim of the present study is to investigate the osteogenic and angiogenic potential of coated Mg-based implants in a sheep cranial defect model. Although their osteogenic potential was studied to some extent, their potential to regenerate vascularized bone formation was not studied in detail. We have studied the potential of magnesium-calcium (MgCa)-based alloys modified with zinc (Zn)- or gallium (Ga)-doped calcium phosphate (CaP) coatings as a strategy to control their degradation rate while enhancing bone regeneration capacity. MgCa and its implants with CaP coatings (MgCa/CaP) as undoped or as doped with Zn or Ga (MgCa/CaP + Zn and MgCa/CaP + Ga, respectively) were implanted in bone defects created in the sheep cranium. MgCa implants degraded faster than the others at 4 weeks postop and the weight loss was ca. 50%, while it was ca. 15% for MgCa/CaP and <10% in the presence of Zn and Ga with CaP coating. Scanning electron microscopy (SEM) analysis of the implant surfaces also revealed that the MgCa implants had the largest degree of structural breakdown of all the groups. Radiological evaluation revealed that surface modification with CaP to the MgCa implants induced better bone regeneration within the defects as well as the enhancement of bone-implant surface integration. Bone volume (%) within the defect was ca. 25% in the case of MgCa/CaP + Ga, while it was around 15% for undoped MgCa group upon micro-CT evaluation. This >1.5-fold increase in bone regeneration for MgCa/CaP + Ga implant was also observed in the histopathological examination of the H&E- and Masson's trichrome-stained sections. Immunohistochemical analysis of the bone regeneration (antiosteopontin) and neovascularization (anti-CD31) at the defect sites revealed >2-fold increase in the expression of the markers in both Ga- and Zn-doped, CaP-coated implants. Zn-doped implants further presented low inflammatory reaction, notable bone regeneration, and neovascularization among all the implant groups. These findings indicated that Ga- and Zn-doped CaP coating is an important strategy to control the degradation rate as well as to achieve enhanced bone regeneration capacity of the implants made of Mg-based alloys.


Subject(s)
Alloys , Calcium Phosphates , Coated Materials, Biocompatible , Gallium , Magnesium , Osteogenesis , Skull , Zinc , Animals , Zinc/chemistry , Zinc/pharmacology , Sheep , Skull/drug effects , Skull/pathology , Skull/injuries , Osteogenesis/drug effects , Magnesium/pharmacology , Gallium/chemistry , Gallium/pharmacology , Alloys/chemistry , Alloys/pharmacology , Coated Materials, Biocompatible/chemistry , Coated Materials, Biocompatible/pharmacology , Calcium Phosphates/chemistry , Calcium Phosphates/pharmacology , Bone Regeneration/drug effects , Calcium/metabolism , Absorbable Implants
9.
Int Wound J ; 21(6): e14940, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38888416

ABSTRACT

Bacterial infection is the most common complication in wound healing, highlighting an urgent need for the development of innovative antibacterial technologies and treatments to address the growing threats posed by bacterial infections. Black phosphorus nanosheets (BPNSs), as a promising two-dimensional nanomaterial, have been utilized in treating infected wounds. However, BP's limited stability restricts its application. In this study, we enhance BP's stability and its antibacterial properties by anchoring gallium ions (Ga3+) onto BP's surface, creating a novel antibacterial platform. This modification reduces BP's electron density and enhances its antibacterial capabilities through a synergistic effect. Under near-infrared (NIR) irradiation, the BP/Ga3+ combination exerts antibacterial effects via photothermal therapy (PTT) and photodynamic therapy (PDT), while also releasing Ga3+. The Ga3+ employ a 'Trojan horse strategy' to disrupt iron metabolism, significantly boosting the antibacterial efficacy of the complex. This innovative material offers a viable alternative to antibiotics and holds significant promise for treating infected wounds and aiding skin reconstruction.


Subject(s)
Anti-Bacterial Agents , Gallium , Phosphorus , Wound Healing , Gallium/pharmacology , Gallium/therapeutic use , Wound Healing/drug effects , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Humans , Animals , Nanostructures/therapeutic use , Wound Infection/drug therapy , Photochemotherapy/methods , Bacterial Infections/drug therapy , Mice , Photothermal Therapy/methods
10.
Nanotechnology ; 35(36)2024 Jun 19.
Article in English | MEDLINE | ID: mdl-38861946

ABSTRACT

Breast cancer is one of the most basilisk cancers for women due to its high mortality rate which can be prevented drastically with early-stage detection. In this work, the adsorption mechanism of two volatile organic compounds that are present in the breath of breast cancer patients, 2-Methyloctane and 3, 3-Dimethylpentane, has been investigated on aluminum phosphide nanotubes (AlPNT) and gallium phosphide nanotubes (GaPNT) in order to understand their feasibility as sensor materials to diagnosis breast cancer at early stage. We have used the quantum mechanical approach by employing density functional theory using B3LYP-D3 hybrid potential for noncovalent interaction along with the LanL2DZ basis in the Gaussian 09 software package. The adsorption properties analyses suggest that GaPNT exhibits better sensing behavior as well as proclaims 12.6% greater adsorption energy for 2-Methyloctane and 9.4% greater adsorption energy for 3, 3-Dimethylpentane than AlPNT. Other structural and electric properties analyses satisfy this conclusion and suggest that GaPNT exhibits higher stability than AlPNT and could possibly be a potential candidate for developing biosensors to detect breast cancer at the preliminary stages.


Subject(s)
Breast Neoplasms , Density Functional Theory , Nanotubes , Phosphines , Breast Neoplasms/diagnosis , Humans , Female , Nanotubes/chemistry , Phosphines/chemistry , Adsorption , Gallium/chemistry , Octanes/chemistry , Volatile Organic Compounds/analysis , Biosensing Techniques/methods
11.
Lab Chip ; 24(13): 3284-3293, 2024 Jun 25.
Article in English | MEDLINE | ID: mdl-38847194

ABSTRACT

The prostate-specific antigen (PSA) test is considered an important way for preoperative diagnosis and accurate screening of prostate cancer. Current antigen detection methods, including radioimmunoassay, enzyme-linked immunosorbent assay and microfluidic electrochemical detection, feature expensive equipment, long testing time and poor stability. Here, we propose a portable biosensor composed of electrolyte-gated amorphous indium gallium zinc oxide (a-IGZO) transistors with an extended gate, which can achieve real-time, instant PSA detection at a low operating voltage (<2 V) owing to the liquid-free ionic conductive elastomer (ICE) serving as the gate dielectric. The electric double layer (EDL) capacitance in ICE enhances the accumulation of carriers in the IGZO channel, leading to strong gate modulation, which enables the IGZO transistor to have a small subthreshold swing (<0.5 V dec-1) and a high on-state current (∼4 × 10-4 A). The separate, biodegradable, and pluggable sensing pad, serving as an extended gate connected to the IGZO transistor, prevents contamination and depletion arising from direct contact with biomolecular buffers, enabling the IGZO transistor to maintain superior electronic performance for at least six months. The threshold voltage and channel current of the transistor exhibit excellent linear response to PSA molecule concentrations across five orders of magnitude ranging from 1 fg mL-1 to 10 pg mL-1, with a detection limit of 400 ag mL-1 and a detection time of ∼5.1 s. The fabricated biosensors offer a point-of-care system for antigen detection, attesting the feasibility of the electrolyte-gated transistors in clinical screening, healthcare diagnostics and biological management.


Subject(s)
Biosensing Techniques , Electrolytes , Gallium , Prostate-Specific Antigen , Transistors, Electronic , Zinc Oxide , Prostate-Specific Antigen/analysis , Humans , Electrolytes/chemistry , Zinc Oxide/chemistry , Biosensing Techniques/instrumentation , Gallium/chemistry , Male , Indium/chemistry , Equipment Design
12.
Arch Microbiol ; 206(7): 304, 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38878097

ABSTRACT

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.


Subject(s)
Anti-Bacterial Agents , Biofilms , Gallium , Methicillin-Resistant Staphylococcus aureus , Microbial Sensitivity Tests , Staphylococcus aureus , Vancomycin , Gallium/pharmacology , Vancomycin/pharmacology , Anti-Bacterial Agents/pharmacology , Methicillin-Resistant Staphylococcus aureus/drug effects , Biofilms/drug effects , Staphylococcus aureus/drug effects , Drug Synergism , Reactive Oxygen Species/metabolism , Staphylococcal Infections/drug therapy , Staphylococcal Infections/microbiology , Humans
13.
Biomater Adv ; 162: 213922, 2024 Sep.
Article in English | MEDLINE | ID: mdl-38878645

ABSTRACT

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.


Subject(s)
Gallium , Nanoparticles , Osteoclasts , Osteogenesis , Gallium/chemistry , Gallium/pharmacology , Animals , Mice , Osteoclasts/drug effects , Nanoparticles/chemistry , Osteogenesis/drug effects , Silicon Dioxide/chemistry , Silicon Dioxide/pharmacology , RAW 264.7 Cells , Porosity , Cell Differentiation/drug effects
14.
Opt Express ; 32(10): 16867-16878, 2024 May 06.
Article in English | MEDLINE | ID: mdl-38858883

ABSTRACT

In this paper, a highly integrated terahertz (THz) biosensor is proposed and implemented, which pioneered the preparation of low-temperature gallium arsenide (LT-GaAs) thin film photoconductive antenna (PCA) on the sensor for direct generation and detection of THz waves, simplifying complex terahertz time-domain spectroscopy (THz-TDS) systems. A latch type metasurface is deposited in the detection region to produce a resonance absorption peak at 0.6 THz that is independent of polarisation. Microfluidics is utilised and automatic injection is incorporated to mitigate the experimental effects of hydrogen bond absorption of THz waves in aqueous-based environment. Additionally, cell damage is minimised by regulating the cell flow rate. The biosensor was utilised to detect the concentration of three distinct sizes of bacteria with successful results. The assay was executed as a proof of concept to detect two distinct types of breast cancer cells. Based on the experimental findings, it has been observed that the amplitude and blueshift of the resonance absorption peaks have the ability to identify and differentiate various cancer cell types. The findings of this study introduce a novel approach for developing microfluidic THz metasurface biosensors that possess exceptional levels of integration, sensitivity, and rapid label-free detection capabilities.


Subject(s)
Arsenicals , Biosensing Techniques , Gallium , Terahertz Spectroscopy , Gallium/chemistry , Arsenicals/chemistry , Biosensing Techniques/instrumentation , Terahertz Spectroscopy/instrumentation , Humans , Equipment Design , Microfluidics/instrumentation
15.
Biomed Mater ; 19(5)2024 Jul 04.
Article in English | MEDLINE | ID: mdl-38917820

ABSTRACT

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.


Subject(s)
Cell Survival , Gallium , Osteogenesis , Gallium/chemistry , Animals , Humans , Cell Line, Tumor , Osteogenesis/drug effects , Cell Survival/drug effects , Mice , Zinc/chemistry , Rats , Glass Ionomer Cements/chemistry , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Materials Testing , Bone Neoplasms/drug therapy , Osteoblasts/drug effects , Female , Breast Neoplasms/drug therapy , Breast Neoplasms/pathology , Biocompatible Materials/chemistry , Biocompatible Materials/pharmacology , Lung Neoplasms/drug therapy , Lung Neoplasms/pathology
16.
Biomaterials ; 310: 122619, 2024 Oct.
Article in English | MEDLINE | ID: mdl-38805955

ABSTRACT

The hypometabolic and nutrient-limiting condition of dormant bacteria inside biofilms reduces their susceptibility to antibacterial agents, making the treatment of biofilm-dominating chronic infections difficult. Herein, we demonstrate an intratracheal aerosolized maltohexaose-modified catalase-gallium integrated nanosystem that can 'wake up' dormant Pseudomonas aeruginosa biofilm to increase the metabolism and nutritional iron demand by reconciling the oxygen gradient. The activated bacteria then enhance suicidal gallium uptake since gallium acts as a 'Trojan horse' to mimic iron. The internalized gallium ions disrupt biofilms by interfering with the physiological processes of iron ion acquisition and utilization, biofilm formation, and quorum sensing. Furthermore, aerosol microsprayer administration and bacteria-specific maltohexaose modification enable accumulation at biofilm-infected lung and targeted release of gallium into bacteria to improve the therapeutic effect. This work provides a potential strategy for treating infection by reversing the dormant biofilm's resistance condition.


Subject(s)
Biofilms , Gallium , Pseudomonas aeruginosa , Biofilms/drug effects , Gallium/chemistry , Gallium/pharmacology , Pseudomonas aeruginosa/drug effects , Pseudomonas aeruginosa/physiology , Animals , Pseudomonas Infections/drug therapy , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Mice , Lung/microbiology , Quorum Sensing/drug effects , Chronic Disease , Iron/metabolism
17.
J Med Chem ; 67(11): 9054-9068, 2024 Jun 13.
Article in English | MEDLINE | ID: mdl-38781403

ABSTRACT

Molecular hybridization is a well-established strategy for developing new drugs. In the pursuit of promising photosensitizers (PSs) with enhanced photodynamic therapy (PDT) efficiency, a series of novel 5-fluorouracil (5FU) gallium corrole conjugates (1-Ga-4-Ga) were designed and synthesized by hybridizing a chemotherapeutic drug and PSs. Their photodynamic antitumor activity was also evaluated. The most active complex (2-Ga) possesses a low IC50 value of 0.185 µM and a phototoxic index of 541 against HepG2 cells. Additionally, the 5FU-gallium corrole conjugate (2-Ga) exhibited a synergistic increase in cytotoxicity under irradiation. Excitedly, treatment of HepG2 tumor-bearing mice with 2-Ga under irradiation could completely ablate tumors without harming normal tissues. 2-Ga-mediated PDT could disrupt mitochondrial function, cause cell cycle arrest in the sub-G1 phase, and activate the cell apoptosis pathway by upregulating the cleaved PARP expression and the Bax/Bcl-2 ratios. This work provides a useful strategy for the design of new corrole-based chemo-photodynamic therapy drugs.


Subject(s)
Apoptosis , Fluorouracil , Gallium , Photochemotherapy , Photosensitizing Agents , Porphyrins , Fluorouracil/pharmacology , Fluorouracil/chemistry , Fluorouracil/therapeutic use , Humans , Gallium/chemistry , Gallium/pharmacology , Animals , Porphyrins/pharmacology , Porphyrins/chemistry , Porphyrins/therapeutic use , Photosensitizing Agents/pharmacology , Photosensitizing Agents/chemistry , Photosensitizing Agents/chemical synthesis , Photosensitizing Agents/therapeutic use , Mice , Apoptosis/drug effects , Hep G2 Cells , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/chemical synthesis , Mice, Inbred BALB C , Mice, Nude
18.
BMC Oral Health ; 24(1): 539, 2024 May 08.
Article in English | MEDLINE | ID: mdl-38720276

ABSTRACT

BACKGROUND: This study aimed to demonstrate the efficacy of erbium, chromium-doped:yttrium, scandium, gallium, and garnet (Er,Cr:YSGG) laser-assisted nonsurgical periodontal therapy in periodontitis patients during 8 weeks of healing. METHODS: A split-mouth, single-blinded, randomized controlled clinical trial was conducted on 12 patients diagnosed with stage III/IV periodontitis and had a minimum of two teeth with probing pocket depth (PPD) > 5 mm in at least two quadrants. Upon randomization, each quadrant was assigned for conventional scaling and root planing (SRP) procedure or laser-assisted therapy (SRP + laser) using radial firing tip (RFPT 5, Biolase). Clinical measurements and gingival crevicular fluid collection were performed for statistical analysis. RESULTS: In the initial statistical analysis on the whole subject teeth, modified gingival index (MGI) reduction was greater in test group at 1(P = 0.0153), 4 (P = 0.0318), and 8 weeks (P = 0.0047) compared to the control in the same period. PPD reduction at 4 weeks in test group was -1.67 ± 0.59 showing significant difference compared to the control (-1.37 ± 0.63, P = 0.0253). When teeth with mean PPD ≥5 mm were sorted, MGI decrease was significantly greater in test group at 1 (P=0.003) and 8 week (P=0.0102) follow-ups. PPD reduction was also significantly greater in test group at 4 week period (-1.98 ± 0.55 vs -1.58 ± 0.56, test vs control, P=0.0224). CONCLUSIONS: Er,Cr:YSGG-assisted periodontal therapy is beneficial in MGI and PPD reductions during early healing period.


Subject(s)
Dental Scaling , Gingival Crevicular Fluid , Lasers, Solid-State , Periodontal Index , Periodontal Pocket , Root Planing , Humans , Single-Blind Method , Female , Male , Lasers, Solid-State/therapeutic use , Adult , Dental Scaling/methods , Gingival Crevicular Fluid/chemistry , Middle Aged , Root Planing/methods , Periodontal Pocket/therapy , Wound Healing , Treatment Outcome , Follow-Up Studies , Chromium/therapeutic use , Periodontitis/therapy , Gallium/therapeutic use
19.
J Photochem Photobiol B ; 256: 112928, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38723545

ABSTRACT

INTRODUCTION: Emerging antibiotic resistance among bacterial pathogens has forced an urgent need for alternative non-antibiotic strategies development that could combat drug resistant-associated infections. Suppression of virulence of ESKAPE pathogens' by targeting multiple virulence traits provides a promising approach. OBJECTIVES: Here we propose an iron-blocking antibacterial therapy based on a cationic heme-mimetic gallium porphyrin (GaCHP), which antibacterial efficacy could be further enhanced by photodynamic inactivation. METHODS: We used gallium heme mimetic porphyrin (GaCHP) excited with light to significantly reduce microbial viability and suppress both the expression and biological activity of several virulence traits of both Gram-positive and Gram-negative ESKAPE representatives, i.e., S. aureus and P. aeruginosa. Moreover, further improvement of the proposed strategy by combining it with routinely used antimicrobials to resensitize the microbes to antibiotics and provide enhanced bactericidal efficacy was investigated. RESULTS: The proposed strategy led to substantial inactivation of critical priority pathogens and has been evidenced to suppress the expression and biological activity of multiple virulence factors in S. aureus and P. aeruginosa. Finally, the combination of GaCHP phototreatment and antibiotics resulted in promising strategy to overcome antibiotic resistance of the studied microbes and to enhance disinfection of drug resistant pathogens. CONCLUSION: Lastly, considering high safety aspects of the proposed treatment toward host cells, i.e., lack of mutagenicity, no dark toxicity and mild phototoxicity, we describe an efficient alternative that simultaneously suppresses the functionality of multiple virulence factors in ESKAPE pathogens.


Subject(s)
Anti-Bacterial Agents , Gallium , Heme , Photosensitizing Agents , Porphyrins , Pseudomonas aeruginosa , Staphylococcus aureus , Photosensitizing Agents/pharmacology , Photosensitizing Agents/chemistry , Gallium/chemistry , Gallium/pharmacology , Porphyrins/chemistry , Porphyrins/pharmacology , Pseudomonas aeruginosa/drug effects , Staphylococcus aureus/drug effects , Heme/chemistry , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Virulence/drug effects , Microbial Sensitivity Tests , Light , Drug Resistance, Bacterial/drug effects
20.
Int J Biol Macromol ; 271(Pt 1): 132494, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38788874

ABSTRACT

The synthesis of liquid metal-infused hydrogels, typically constituted by polyacrylamide networks crosslinked through covalent bonds, often encounters a conundrum: they exhibit restricted extensibility and a diminished capacity for self-repair, owing to the inherently irreversible nature of the covalent linkages. This study introduces a hydrophobically associated hydrogel embedding gallium (Ga)-droplets, realized through the in situ free radical copolymerization of hydrophobic hexadecyl methacrylate (HMA) and hydrophilic acrylamide (AM) in a milieu containing xanthan gum (XG) and PEDOT:PSS, which co-stabilizes the Ga-droplets. The Ga-droplets, synergistically functioning as conductive agents alongside PEDOT:PSS, also expedite the hydrogel's formation. The resultant XG/PEDOT:PSS-Ga-P(AM-HMA) hydrogel is distinguished by its remarkable extensibility (2950 %), exceptional toughness (3.28 MJ/m3), superior adherence to hydrophobic, smooth substrates, and an innate ability for hydrophobic-driven self-healing. As a strain sensing medium, this hydrogel-based sensor exhibits heightened sensitivity (gauge factor = 12.66), low detection threshold (0.1 %), and robust durability (>500 cycles). Furthermore, the inclusion of glycerol endows the XG/PEDOT:PSS-Ga-P(AM-HMA) hydrogel with anti-freezing properties without compromising its mechanical integrity and sensing acumen. This sensor adeptly captures a spectrum of human movements, from the nuanced radial pulse to extensive joint articulations. This research heralds a novel approach for fabricating multifaceted PAM-based hydrogels with toughness and superior sensing capabilities.


Subject(s)
Hydrogels , Hydrophobic and Hydrophilic Interactions , Polymers , Polysaccharides, Bacterial , Hydrogels/chemistry , Polysaccharides, Bacterial/chemistry , Polymers/chemistry , Polystyrenes/chemistry , Gallium/chemistry , Metals/chemistry , Bridged Bicyclo Compounds, Heterocyclic
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