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Antimicrobial resistance is a silent pandemic considered a public health concern worldwide. Strategic therapies are needed to replace antibacterials that are now ineffective. One approach entails the use of well-known antibacterials along with adjuvants that possess non-antibiotic properties but can extend the lifespan and enhance the effectiveness of the treatment, while also improving the suppression of resistance. In this regard, a group of uniform materials based on organic salts (GUMBOS) presents an alternative to this problem allowing the combination of antibacterials with adjuvants. Fluoroquinolones are a family of antibacterials used to treat respiratory and urinary tract infections with broad-spectrum activity. Ciprofloxacin and moxifloxacin-based GUMBOS were synthesized via anion exchange reactions with lithium and sodium salts. Structural characterization, thermal stability and octanol/water partition ratios were evaluated. The antibacterial profiles of most GUMBOS were comparable to their cationic counterparts when tested against Gram-positive S. aureus and Gram-negative E. coli, except for deoxycholate anion, which demonstrated the least effective antibacterial activity. Additionally, some GUMBOS were less cytotoxic to L929 fibroblast cells and non-hemolytic to red blood cells. Therefore, these agents exhibit promise as an alternative approach to combining drugs for treating infections caused by resistant bacteria.
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Fluoroquinolonas , Sais , Fluoroquinolonas/farmacologia , Sais/farmacologia , Sais/química , Escherichia coli , Staphylococcus aureus , Antibacterianos/química , Ânions , Testes de Sensibilidade MicrobianaRESUMO
Diabetic foot ulcers are characterized by hypoxia. For many patients, hyperbaric oxygen (HBO) therapy is the last recourse for saving the limb from amputation, for which the molecular basis is not understood. We previously identified the active form of matrix metalloproteinase-9 (MMP-9) as responsible for diabetic foot ulcer's recalcitrance to healing. Transcription of mmp-9 to the inactive zymogen is upregulated during hypoxia. Activation of the zymogen is promoted by proteases and reactive oxygen species (ROS). We hypothesized that the dynamics of these two events might lead to a lowering of active MMP-9 levels in the wounded tissue. We employed the full-thickness excisional db/db mouse model to study wound healing, and treated the mice to 3.0 atm of molecular oxygen for 90 minutes, 5 days per week for 10 days in an HBO research chamber. Treatment with HBO accelerated diabetic wound healing compared to untreated mice, with more completed and extended reepithelialization. We imaged the wounds for ROS in vivo with a luminol-based probe and found that HBO treatment actually decreases ROS levels. The levels of superoxide dismutase, catalase, and glutathione peroxidase-enzymes that turn over ROS-increased after HBO treatment, hence the observation of decreased ROS. Since ROS levels are lowered, we explored the effect that this would have on activation of MMP-9. Quantitative analysis with an affinity resin that binds and pulls down the active MMPs exclusively, coupled with proteomics, revealed that HBO treatment indeed reduces the active MMP-9 levels. This work for the first time demonstrates that diminution of active MMP-9 is a contributing factor and a mechanism for enhancement of diabetic wound healing by HBO therapy.
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Diabetes Mellitus Tipo 2/metabolismo , Pé Diabético/metabolismo , Oxigenoterapia Hiperbárica , Metaloproteinase 9 da Matriz/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Cicatrização , Animais , Catalase/metabolismo , Modelos Animais de Doenças , Precursores Enzimáticos/metabolismo , Glutationa Peroxidase/metabolismo , Camundongos , Receptores para Leptina/genética , Superóxido Dismutase/metabolismoRESUMO
Herein, we examine two sensing schemes for detection and discrimination of chlorinated volatile organic compounds (VOCs). In this work, phosphonium ionic liquids (ILs) were synthesized and vapor sensing properties examined and compared to phosphonium IL-polymer composites. Pure IL sensors were used to develop a QCM-based multisensory array (MSA), while IL-polymer composites were used to develop an MSA and virtual sensor arrays (VSAs). It was found that by employing the composite MSA, five chlorinated VOCs were accurately discriminated at 95.56%, which was an increase in accuracy as compared to pure ILs MSA (84.45%). Data acquired with two out of three VSAs allowed discrimination of chlorinated VOCs with 100% accuracy. These studies have provided greater insight into the benefits of incorporating polymers in coating materials for enhanced discrimination accuracies of QCM-based sensor arrays. To the best of our knowledge, this is the first report of a QCM-based VSA for discrimination of closely related chlorinated VOCs.
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Quality checks, assessments, and the assurance of food products, raw materials, and food ingredients is critically important to ensure the safeguard of foods of high quality for safety and public health. Nevertheless, quality checks, assessments, and the assurance of food products along distribution and supply chains is impacted by various challenges. For instance, the development of portable, sensitive, low-cost, and robust instrumentation that is capable of real-time, accurate, and sensitive analysis, quality checks, assessments, and the assurance of food products in the field and/or in the production line in a food manufacturing industry is a major technological and analytical challenge. Other significant challenges include analytical method development, method validation strategies, and the non-availability of reference materials and/or standards for emerging food contaminants. The simplicity, portability, non-invasive, non-destructive properties, and low-cost of NIR spectrometers, make them appealing and desirable instruments of choice for rapid quality checks, assessments and assurances of food products, raw materials, and ingredients. This review article surveys literature and examines current challenges and breakthroughs in quality checks and the assessment of a variety of food products, raw materials, and ingredients. Specifically, recent technological innovations and notable advances in quartz crystal microbalances (QCM), electroanalytical techniques, and near infrared (NIR) spectroscopic instrument development in the quality assessment of selected food products, and the analysis of food raw materials and ingredients for foodborne pathogen detection between January 2019 and July 2020 are highlighted. In addition, chemometric approaches and multivariate analyses of spectral data for NIR instrumental calibration and sample analyses for quality assessments and assurances of selected food products and electrochemical methods for foodborne pathogen detection are discussed. Moreover, this review provides insight into the future trajectory of innovative technological developments in QCM, electroanalytical techniques, NIR spectroscopy, and multivariate analyses relating to general applications for the quality assessment of food products.
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Técnicas de Microbalança de Cristal de Quartzo , Espectroscopia de Luz Próxima ao Infravermelho , Calibragem , Indústria de Processamento de Alimentos , Análise MultivariadaRESUMO
Herein, we report on the role of endocytosis in the selective chemotherpeutic toxicity of rhodamine 6G (R6G) based nanomaterials, i.e., nanoGUMBOS, that are derived from a group of uniform materials based on organic salts (GUMBOS). Evaluation of cellular uptake in the presence and absence of endocytosis inhibitors suggests nanoGUMBOS internalization via clathrin-mediated endocytosis in cancer cells and reveals lack of endocytic internalization in normal cells. Results from characterization of these nanomaterials suggest that endocytic internalization in cancer cells leads to nanoGUMBOS dissociation within the endosomal environment. This ultimately results in selective cytotoxicity of the nanoGUMBOS for cancer cells with no toxicity toward normal cells under examined conditions. Following examination of the selectivity mechanism, in vivo investigations were performed to examine potential therapeutic properties of these nanoparticles. Remarkably, nanoGUMBOS treatment using a mouse xenograft model reduced the tumor volume by 50% suggesting retention of in vitro therapeutic properties in vivo. These results corroborate the selective behavior of nanoGUMBOS and demonstrate their in vivo therapeutic effects, providing further insight into the possible use of these nanomaterials as potential chemotherapeutic agents.
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Endocitose/efeitos dos fármacos , Nanoestruturas/toxicidade , Rodaminas/toxicidade , Animais , Neoplasias da Mama/metabolismo , Linhagem Celular , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Feminino , Citometria de Fluxo , Humanos , Camundongos Nus , Nanoestruturas/química , Rodaminas/químicaRESUMO
Enzyme extraction using aqueous two-phase systems (ATPS) has been increasingly used as a primary recovery technique which integrates the clarification, concentration and partial purification of important biomolecules from their natural source in a single step. The goal of this work was to optimize the extraction of trypsin from pancreas homogenate with polyethylene glycol and sodium citrate (PEG/NaCit) ATPS by using the tools of experimental design. The variables NaCl concentration - added inert salt -, the top/bottom phase volume ratio - Vr - and the biomass loaded into the system - in percentage - were selected as the main factors in the trypsin extraction. The yield (%) and the purification factor of trypsin were considered the responses to be optimized. The central composite design and the response surface analysis proved to be suitable tools for a quick and efficient study. As a result, the optimal extraction conditions in PEG3350/NaCit system were 3.34% wt/wt for NaCl concentration, a biomass load which represented 9.30% wt/wt of the total ATPS mass and 6.37 top/bottom volume ratio giving a purification factor of 2.55 and a yield of 99.7% in top phase.
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Bioquímica/métodos , Citratos/química , Pâncreas/enzimologia , Polietilenoglicóis/química , Tripsina/isolamento & purificação , Animais , Bovinos , Concentração de Íons de Hidrogênio , Extratos Pancreáticos/metabolismo , Análise de Regressão , Reprodutibilidade dos Testes , Citrato de Sódio , ÁguaRESUMO
Wearing masks to prevent infectious diseases, especially during the COVID-19 pandemic, is common. However, concerns arise about inhalation exposure to microplastics (MPs) when disposable masks are improperly reused. In this study, we assessed whether disposable masks release inhalable MPs when reused in simulated wearing conditions. All experiments were conducted using a controlled test chamber setup with a constant inspiratory flow. Commercially available medical masks with a three-layer material, composition comprising polypropylene (PP in the outer and middle layers) and polyethylene (PE in the inner layer), were used as the test material. Brand-new masks with and without hand rubbing, as well as reused medical masks, were tested. Physical properties (number, size, and shape) and chemical composition (polymers) were identified using various analytical techniques such as fluorescence staining, fluorescence microscopy, and micro-Fourier Transform Infrared Spectroscopy (µFTIR). Scanning Electron Microscopy (SEM) was used to scrutinize the surface structure of reused masks across different layers, elucidating the mechanism behind the MP generation. The findings revealed that brand-new masks subjected to hand rubbing exhibited a higher cumulative count of MPs, averaging approximately 1.5 times more than those without hand rubbing. Fragments remained the predominant shape across all selected size classes among the released MPs from reused masks, primarily through a physical abrasion mechanism, accounting for >90 % of the total MPs. The numbers of PE particles were higher than PP particles, indicating that the inner layer of the mask contributed more inhalable MPs than the middle and outer layers combined. The released MPs from reused masks reached their peak after 8 h of wearing. This implies that regularly replacing masks serves as a preventive measure and mitigates associated health risks of inhalation exposure to MPs.
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Exposição por Inalação , Poluentes Químicos da Água , Humanos , Exposição por Inalação/prevenção & controle , Máscaras , Microplásticos , Pandemias , Plásticos , PolietilenoRESUMO
Tuning the 8-anilino-1-naphthalenesulfonic acid (ANS) structure usually requires harsh conditions and long reaction times, which can result in low yields. Herein, ANS was modified to form an ANS group of uniform materials based on organic salts (GUMBOS), prepared with simple metathesis reactions and distinct cations, namely tetrabutylammonium (N4444), tetrahexylammonium (N6666), and tetrabutylphosphonium (P4444). These ANS-based GUMBOS were investigated as fluorescent probes for membrane binding studies with four proteins having distinct physicochemical properties. Liposomes of 1,2-dimyristoyl-sn-glycero-3-phosphocholine were employed as membrane models as a result of their ability to mimic the structure and chemical composition of cell membranes. Changes in fluorescence intensity were used to monitor protein binding to liposomes, and adsorption data were fitted to a Freundlich-like isotherm. It was determined that [N4444][ANS] and [P4444][ANS] GUMBOS have enhanced optical properties and lipophilicity as compared to parent ANS. As a result, these two GUMBOS were selected for subsequent protein-membrane binding studies. Both [N4444][ANS] and [P4444][ANS] GUMBOS and parent ANS independently reached membrane saturation within the same concentration range. Furthermore, distinct fluorescence responses were observed upon the addition of proteins to each probe, which demonstrates the impact of properties such as lipophilicity on the binding process. The relative maintenance of binding cooperativity and maximum fluorescence intensity suggests that proteins compete with ANS-based probes for the same membrane binding sites. Finally, this GUMBOS-based approach is simple, rapid, and involves relatively small amounts of reagents, making it attractive for high-throughput purposes. These results presented herein can also provide relevant information for designing GUMBOS with ameliorated properties.
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Naftalenossulfonato de Anilina , Lipossomos , Ligação Proteica , Naftalenossulfonato de Anilina/química , Lipossomos/química , Corantes Fluorescentes/química , Espectrometria de Fluorescência/métodos , Materiais Biomiméticos/química , Sais/química , Compostos de Amônio Quaternário/químicaRESUMO
For the first time, the spectrofluorimetric properties of estrone (E1), 17ß-estradiol (E2), estriol (E3), and 17α-ethinylestradiol (EE2) are studied in aqueous solutions after the addition of native and derivative cyclodextrins. In contrast to previous reports, the behavior of the systems is analysed in the absence of organic solvents able to modify the guest-host interaction. The significant differences between the obtained association constants with those reported in solvent mixtures are shown and discussed. In order to evaluate the influence of both the estrogen structure and the presence of cyclodextrin substituents on the inclusion phenomenon, fluorescent and acid-base behaviors of the systems are compared and discussed. The interaction of estrogens with micellar media formed by selected surfactants is also studied. It is demonstrated that estrogen-cyclodextrin complexes in aqueous solution are useful for improving fluorimetric detection limits and, since cyclodextrins are non-toxic and mitigate most of the solubility problems which require the use of organic solvents, the studied complexes are excellent candidates for extraction, separation, pre-concentration and removal processes maintaining the principles of the green analytical chemistry.
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Ciclodextrinas/análise , Estrogênios/análise , Espectrometria de Fluorescência/métodos , Água/análise , Ciclodextrinas/química , Estrogênios/químicaRESUMO
Herein, hydrophobic coating materials are reported for QCM detection of VOCs under dry and humid conditions. In this study, IR780-based GUMBOS ([IR780][OTf] and [IR780][NTf2]) were synthesized using an ion exchange reaction and the anions trifluoromethanesulfonimide ([OTf]) and bisperfluoromethanesulfonimide ([NTf2]). The parent iodide salts and GUMBOS ([IR780][I]), [IR780][OTf], and [IR780][NTf2]) were characterized using several analytical techniques. These salts were then employed as sensor coatings on quartz crystal resonators using an electrospray coating method. These sensors were exposed to four flow ratios of five common VOCs in the absence and presence of 10 vol% water. Fundamental frequency responses were recorded and further employed as input variables to develop highly accurate multi-sensor arrays (MSAs). Accuracy was better than 78.3% without water, and better than 91.7% in the presence of water. When multi-harmonic responses were evaluated as input variables to assess discrimination ability for each sensor, highly accurate virtual sensor arrays (VSAs) were developed using each GUMBOS coating. In the case of [IR780][NTf2], a slight improvement in discrimination was achieved in the presence of water (95%) versus the absence of water. Moreover, this study highlights development of readily synthesized hydrophobic coatings of IR780-based GUMBOS for potential detection and discrimination of VOCs in aqueous systems.
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In recent years, advanced materials with properties resembling biological systems, particularly artificial muscles, have received intense scrutiny. This is because the interesting conformational shape characteristics of such materials have benefited a variety of technologies, including textiles, 3D printing, and medical devices. Although a multitude of shape memory properties have been studied and developed in recent years, self-healing of these polymers after puncture or rupture has also become a major area of study. Most techniques for detection of such processes are mechanically based and require considerable hands-on monitoring. Thus, a rapid visual detection method for self-healing is highly desirable. Herein, we describe fluorescence studies for rapid detection of self-healing properties of a partially neutralized sodium ionomer poly(ethylene-co-methacrylic acid) (PEMA). In this study, two different fluorophores, parent non-ionic 4,6-dipyrenylpyrimidine and ionic 4,6-dipyrenylpyrimidinium iodide fluorophores, were evaluated as possible sensors of self-healing. Incorporation of these probes via solution blending and compatibility into a PEMA of these fluorophores were evaluated. Thermal characterizations using differential scanning calorimetry were also performed to elucidate physical characteristics of healed sites. Ratiometric fluorescence emission variations were explored within puncture-healed ionomer films and related to Young's modulus properties with good linearity, indicating potential utility of this approach for monitoring elastic modulus properties after healing has occurred. Further statistical analyses of mechanical processes using quadratic discriminant analysis resulted in development of several highly accurate predictive models for determining time since damage healing.
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GUMBOS (Group of Uniform Materials Based on Organic Salts) have recently emerged as interesting materials for protein analysis due to their unique features and high tunability. In this regard, four novel erythrosin B (EB)-based GUMBOS were synthesized and their potential to discriminate among proteins with distinct properties (e.g., size, charge, and hydrophobicity) was assessed. These solid-phase materials were prepared using a single-step metathesis reaction between EB and various phosphonium and ammonium cations, namely tetrabutylphosphonium (P4444+), tributylhexadecylphosphonium (P44416+), tetrabutylammonium (N4444+), and benzyldimethylhexadecylammonium (BDHA+). Subsequently, the effect of pH (3.0, 4.5, and 6.0) and reaction time (5, 10, and 15 min) on the discriminatory power of synthesized GUMBOS was evaluated. Absorption spectra resulting from the interaction between EB-based GUMBOS and proteins were analyzed using partial least squares discriminant analysis (PLSDA). Unlike time, the pH value was determined to have influence over GUMBOS discrimination potential. Correct protein assignments varied from 86.5% to 100.0%, and the best discriminatory results were observed for [P4444]2[EB] and [N4444]2[EB] at pH 6.0. Additionally, these two GUMBOS allowed discrimination of protein mixtures containing different ratios of albumin and myoglobin, which appeared as individualized clusters in the PLSDA scores plots. Overall, this study showcases EB-based GUMBOS as simple synthetic targets to provide a label-free, cost-effective, rapid, and successful approach for discrimination of single proteins and their mixtures.
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Quimiometria , Eritrosina , Proteínas , Sais , Análise EspectralRESUMO
Herein, a solvent-based green recycling procedure is reported for recycling thermoset epoxy resins (TERs) and carbon fiber reinforced epoxy composites (CFRECs) employing ionic liquids (ILs) and alcohols under mild conditions. With melting points less than 100 °C, ILs are defined as organic salts, typically composed of bulky cations with organic or inorganic counteranions. As a result of their unique physical properties such as low vapor pressure, relatively high thermal stability, and multifunctional tunability, these solvents are often classified as "green solvents" as compared to traditional organic solvents. In this study, swelling and dissolution of TER are evaluated in the presence of pure alkyl-methyl-imidazolium ILs, alcohols, and various mixtures of these co-solvents to determine their swelling and depolymerization capacity at mild temperatures in the absence of catalysts. In these studies, three ILs with different alkyl lengths were evaluated: 1-butyl-3-methyl imidazolium chloride ([BMIm][Cl]), 1-hexyl-3-methyl imidazolium bromide ([HMIm][Br]), and 1-octyl-3-methyl imidazolium bromide ([OMIm][Br]) along with two alcohols: ethylene glycol (EG) and glycerol (Gly). The highest swelling capacity of TER at 150 °C was achieved by a combination of [BMIm][Cl] and EG. In addition, swelling and dissolution of TER were evaluated in the presence of several anion variants of 1-butyl-3-methyl-imidazolium ILs with EG. Complete dissolution of both TERs and CFRECs was achieved in 150 min (2.5 h) at 150 °C under atmospheric pressure. Finally, recovery and reuse of the recycled monomer after dissolution were examined. Recovered epoxy monomers employed to synthesize a recycled TER exhibited similar mechanical properties to the parent TER. In addition, it was demonstrated that carbon fibers could be successfully recovered from CFREC using the recycling method detailed in this manuscript.
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A facile method was used to synthesize biocomposites containing differing ratios of hyaluronic acid (HA) and cellulose (CEL). Based on the properties of the individual polymers, the resultant composite materials may have potentially great wound care properties. In the method outlined here, 1-butyl-3-methylimidazolium chloride ([Bmim][Cl]), a simple ionic liquid, was used as the sole solvent without chemical modifiers to dissolve the biopolymers at ratios of 1:1 and 2:1 HA to CEL. This method was completely recyclable since the ionic liquid, [Bmim][Cl], can be recovered. Results from spectroscopic measurements [Fourier transform infrared (FT-IR) and X-ray diffraction (XRD)] confirm the interaction between HA and CEL. Scanning electron microscopy (SEM) images reflect differing biopolymer ratios and the resulting impact on the texture and porosity of these composite materials. The composites exhibited high swelling capacity in various media. These composites were also drug-loaded to examine drug release properties for greater potential in combating Staphylococcus aureus infections.
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Sensitive and selective detection of proteins from complex samples has gained substantial interest within the scientific community. Early and precise detection of key proteins plays an important role in potential clinical diagnosis, treatment of different diseases, and proteomic research. In the study reported here, six different compounds belonging to a group of uniform materials based on organic salts (GUMBOS) have been synthesized using three thiacarbocyanine (TC) dyes and employed as fluorescent sensors. Fluorescence properties of micro- and nanoaggregates of these TC-based GUMBOS formed in phosphate buffer solutions are studied in the absence and presence of seven proteins. Fluorescence response patterns of these TC-based GUMBOS were analyzed by linear discriminant analysis (LDA). The constructed LDA model allowed discrimination of these seven proteins at various concentrations with 100% accuracy. The sensing and discrimination abilities of these TC-based GUMBOS were further evaluated in mixtures of two major proteins, i.e., human serum albumin and hemoglobin. Fluorescence response patterns of these mixtures were analyzed by LDA. This model allowed discrimination of various mixtures with 100% accuracy. Moreover, spiked urine samples were prepared and the responses of these sensors were collected and analyzed by LDA. Remarkably, discrimination of these seven proteins was also achieved with 100% accuracy.
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Proteômica , Sais , Análise Discriminante , Humanos , ProteínasRESUMO
A novel imidazolium-dysprosium-based magnetic nanomaterial, i.e. [C16mim]5[Dy(SCN)8] nanoGUMBOS (nanomaterials fabricated from a group of uniform material based on organic salts), was prepared using a facile method for selective hemoglobin (Hb) isolation. In this nanomaterial, the imidazolium cation serves as a selective Hb affinity group, while dysprosium contributes paramagnetic properties. Through a combination of the advantages of ionic liquids, magnetic adsorbent, and nanoscale solid phase extraction, [C16mim]5[Dy(SCN)8] nanoGUMBOS exhibit great selectivity toward Hb and a favorable extraction efficiency of 95.4% when 1â¯mL of 100⯵g/mL Hb solution is processed with 0.6â¯mg of [C16mim]5[Dy(SCN)8] nanoGUMBOS. As the Hb concentration increased to 800⯵g/mL, the adsorption capacity approached â¼840⯵g/mg. The adsorbed protein is recovered with an elution efficiency of 87% by using 1% SDS solution. This novel nanoGUMBOS solid-phase extraction procedure was successfully applied to selective isolation of Hb from human whole blood and verified using SDS-PAGE. This simple strategy is a novel approach towards fabrication and use of a nanoadsorbent for selective isolation of proteins.
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Disprósio/química , Hemoglobinas/isolamento & purificação , Nanoestruturas/química , Extração em Fase Sólida/métodos , Adsorção , Sangue , Análise Química do Sangue/instrumentação , Análise Química do Sangue/métodos , Dicroísmo Circular , Eletroforese em Gel de Poliacrilamida , Hemoglobinas/química , Humanos , Imidazóis/química , Líquidos Iônicos/química , Fenômenos Magnéticos , Sais/química , Extração em Fase Sólida/instrumentaçãoRESUMO
The near-infrared fluorescent (NIRF) dye, IR780, is recognized as a promising theranostic agent and has been widely investigated for imaging, chemotherapeutic, and phototherapeutic applications. However, its poor photostability and nonselective toxicities toward both cancer and normal cells limit its biological applications. Herein, we introduce the use of GUMBOS (a group of uniform materials based on organic salts) developed through counter-anion exchange with IR780 and subsequent nanomaterials (nanoGUMBOS) formed by complexation with cyclodextrin (CD) for enhanced chemo/photothermal therapy. Such CD-based nanoGUMBOS display improved aqueous stability, photostability, and photothermal effects relative to traditional IR780. The examination of in vitro cytotoxicity reveals that CD-based nanoGUMBOS are selectively toxic toward cancer cells and exhibit synergistically enhanced cytotoxicity toward cancer cells upon NIR laser irradiation. Additionally, in vivo NIRF imaging demonstrated selective accumulation of these nanoGUMBOS within the tumor site, indicating tumor-targeting properties. Further in vivo therapeutic study of these CD-based nanoGUMBOS suggests excellent chemo/photothermal antitumor effects. Using these studies, we herein demonstrate a promising strategy, via conversion of IR780 into nanoGUMBOS, that can be used for improved theranostic cancer treatment.
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Neoplasias da Mama/terapia , Sistemas de Liberação de Medicamentos , Corantes Fluorescentes , Hipertermia Induzida , Indóis , Nanopartículas , Fototerapia , Animais , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Feminino , Corantes Fluorescentes/química , Corantes Fluorescentes/farmacologia , Humanos , Indóis/química , Indóis/farmacologia , Células MCF-7 , Camundongos , Nanopartículas/uso terapêutico , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Herein, a simple counter-ion variation strategy is proposed and demonstrated for design of an array of near infrared IR780-based nanoGUMBOS (nanomaterials from a Group of Uniform Materials Based on Organic Salts) to produce enhanced anticancer activity. These nanomaterials were synthesized by direct nanoengineering of IR780-based GUMBOS using a reprecipitation method, without addition of any other materials. Thus, these novel nanomaterials can serve as carrier-free nanodrugs, providing several distinct advantages over conventional chemotherapeutics. Examination of the size and stability of these nanoGUMBOS indicates formation of approximately 100 nm nanoparticles that are stable under biological conditions. Interestingly, in vitro chemotherapeutic applications of these nanoGUMBOS indicate two to four-fold enhanced toxicity towards breast cancer cells as compared to the parent dye, while still maintaining minimal toxicity towards normal cells. The mechanism of cancer toxicity for these nanoGUMBOS was also examined by a study of their sub-cellular localization as well as using a mitochondrial toxicity assay. Analyses of data from these studies revealed that all nanoGUMBOS primarily accumulate in the mitochondria of cancer cells and produce dysfunction in the mitochondria to induce cell death. Using these studies, we demonstrate tunable properties of IR780-based nanoGUMBOS through simple variation of counter-ions, thus providing a promising strategy for future design of better nanomedicines to be used for cancer therapy.
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Chronic wounds are a complication of diabetes. Treatment for diabetic foot ulcers is complex with little clinical recourse, resulting in 108,000 lower-limb amputations annually in the United States alone. Matrix metalloproteinases (MMPs) play important roles in the pathology and in the repair of chronic wounds. We previously identified active MMP-8 and MMP-9 in wounds of diabetic mice and determined that MMP-8 accelerates wound repair, while MMP-9 is the culprit for the diabetic wound being refractory to healing. Aclerastide, a peptide analog of angiotensin II, recently failed in phase III clinical trials for treatment of diabetic foot ulcers. We demonstrate herein that treatment of wounds of diabetic mice with aclerastide results in elevated levels of reactive oxygen species and of active MMP-9, which is likely an important contributor to the failure of aclerastide in clinical trials.
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Angiotensina II/análogos & derivados , Pé Diabético/tratamento farmacológico , Pé Diabético/metabolismo , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Metaloproteinase 9 da Matriz/metabolismo , Angiotensina II/farmacologia , Angiotensina II/uso terapêutico , Animais , Pé Diabético/enzimologia , Pé Diabético/fisiopatologia , Feminino , Metaloproteinase 8 da Matriz/metabolismo , Camundongos , Falha de Tratamento , Regulação para Cima/efeitos dos fármacos , Cicatrização/efeitos dos fármacosRESUMO
The use of quartz crystal microbalance (QCM) sensor arrays for analyses of volatile organic compounds (VOC) has attracted significant interest in recent years. In this regard, a group of uniformed materials based on organic salts (GUMBOS) has proven to be promising recognition elements in QCM based sensor arrays due to diverse properties afforded by this class of tunable materials. Herein, we examine the application of four novel phthalocyanine based GUMBOS as recognition elements for VOC sensing using a QCM based multisensor array (MSA). These synthesized GUMBOS are composed of copper (II) phthalocyaninetetrasulfonate (CuPcS4) anions coupled with ammonium or phosphonium cations respectively (tetrabutylammonium (TBA), tetrabutylphosphonium (P4444), 3-(dodecyldimethyl-ammonio)propanesulfonate (DDMA), and tributyl-n-octylphosphonium (P4448)). These materials were characterized using ESI-MS and FTIR, while thermal properties were investigated using TGA. Vapor sensing properties of these GUMBOS towards a set of common VOCs at three sample flow rate ratios were examined. Upon exposure to VOCs, each sensor generated analyte specific response patterns that were recorded and analyzed using principal component and discriminant analyses. Use of this MSA allowed discrimination of analytes into different functional group classes (alcohols, chlorohydrocarbons, aromatic hydrocarbons, and hydrocarbons) with 98.6% accuracy. Evaluation of these results provides further insight into the use of phthalocyanine GUMBOS as recognition elements for QCM-based MSAs for VOC discrimination.