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Glyphosate (Gly) is a massively utilized toxic herbicide exceeding its statutory restrictions, causing adverse environmental and health impacts. Engineered nanomaterials, even though are integral to remediate Gly, their practical use is limited due to time and energy driven purifications, and negative environmental impacts. Here, a 3D wide area (~1.6 ± 0.4 cm2) Cu2O nanoparticle supported biotemplate is designed using fish-scale wastes as a sustainable approach for the ultra-efficient and selective hand-remediation of Gly from real-time samples from agro-farms. While the innate metal binding and reducing ability of collagenous scales aided self-synthesis cum grafting of Cu2O, the selective binding potential of Cu2O to Gly facilitated its hand-retrieval; as assessed using optical characterizations, Fourier transform infrared spectroscopy, thermogravimetric analysis and liquid chromatography mass spectrometry. Optimization studies revealed extractions of diverse pay-loads of Gly between 0.1 µg/mL to 40 µg/mL per 80 mg biotemplate grafted with ~6.354 µg of sub-5 nm Cu2O and was exponential to the number of Cu2O@biotemplates. Even though pH and surfactant didn't have any impact on the adsorption of Gly to the Cu2O@biotemplates, increase in the ionic strength led to a drastic increase in the adsorption. Density function theory simulations unveiled the involvement of phosphonic and carboxylic groups of Gly for interaction with Cu2O with a bond length of 1.826 Å and 1.833 Å, respectively. Overall, our sustainably generated, cost-efficient, hand-retrievable Cu2O supported biotemplate can be generalized to extract diverse organophosphorus toxins from agro-farms and other sewage embodiments. SYNOPSIS: Glyphosate is an excessively applied herbicide with potent health hazards and carcinogenicity. Thus, a hand removable Cu2O-supported biotemplate to selectively and efficiently remediate glyphosate from irrigation water is developed.
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Glifosato , Herbicidas , Animales , Herbicidas/química , Agua , Tensoactivos , BioingenieríaRESUMEN
Automated classification of blood cells from microscopic images is an interesting research area owing to advancements of efficient neural network models. The existing deep learning methods rely on large data for network training and generating such large data could be time-consuming. Further, explainability is required via class activation mapping for better understanding of the model predictions. Therefore, we developed a Siamese twin network (STN) model based on contrastive learning that trains on relatively few images for the classification of healthy peripheral blood cells using EfficientNet-B3 as the base model. Hence, in this study, a total of 17,092 publicly accessible cell histology images were analyzed from which 6% were used for STN training, 6% for few-shot validation, and the rest 88% for few-shot testing. The proposed architecture demonstrates percent accuracies of 97.00, 98.78, 94.59, 95.70, 98.86, 97.09, 99.71, and 96.30 during 8-way 5-shot testing for the classification of basophils, eosinophils, immature granulocytes, erythroblasts, lymphocytes, monocytes, platelets, and neutrophils, respectively. Further, we propose a novel class activation mapping scheme that highlights the important regions in the test image for the STN model interpretability. Overall, the proposed framework could be used for a fully automated self-exploratory classification of healthy peripheral blood cells. The whole proposed framework demonstrates the Siamese twin network training and 8-way k-shot testing. The values indicate the amount of dissimilarity.
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Gemelos Siameses , Humanos , Células Sanguíneas , Redes Neurales de la Computación , DescansoRESUMEN
Metal nanoparticles grafted within inert and porous wide-area supports are emerging as recyclable, sustainable catalysts for modern industry applications. Here, we bioengineered gold nanoparticle-based supported catalysts by utilizing the innate metal binding and reductive potential of eggshell as a sustainable strategy. Variable hand-recyclable wide-area three-dimensional catalysts between â¼80 ± 7 and 0.5 ± 0.1 cm2 are generated simply by controlling the size of the support. The catalyst possessed high-temperature stability (300 °C) and compatibility toward polar and nonpolar solvents, electrolytes, acids, and bases facilitating ultra-efficient catalysis of accordingly suspended substrates. Validation was done by large-volume (2.8 liters) dye detoxification, gram-scale hydrogenation of nitroarene, and the synthesis of propargylamine. Moreover, persistent recyclability, monitoring of reaction kinetics, and product intermediates are possible due to physical retrievability and interchangeability of the catalyst. Finally, the bionature of the support permits â¼76.9 ± 8% recovery of noble gold simply by immersing in a royal solution. Our naturally created, low-cost, scalable, hand-recyclable, and resilient supported mega-catalyst dwarfs most challenges for large-scale metal-based heterogeneous catalysis.
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Cancer therapy is a fast-emerging biomedical paradigm that elevates the diagnostic and therapeutic potential of a nanovector for identification, monitoring, targeting, and post-treatment response analysis. Nanovectors of superparamagnetic iron oxide nanoparticles (SPION) are of tremendous significance in cancer therapy because of their inherited high surface area, high reactivity, biocompatibility, superior contrast, and magnetic and photo-inducibility properties. In addition to a brief introduction, we summarize various progressive aspects of nanomagnets pertaining to their production with an emphasis on sustainable biomimetic approaches. Post-synthesis particulate and surface alterations in terms of pharmaco-affinity, liquid accessibility, and biocompatibility to facilitate cancer therapy are highlighted. SPION parameters including particle contrast, core-fusions, surface area, reactivity, photosensitivity, photodynamics, and photothermal properties, which facilitate diverse cancer diagnostics, are discussed. We also elaborate on the concept of magnetism to selectively focus chemotherapeutics on tumors, cell sorting, purification of bioentities, and elimination of toxins. Finally, while addressing the toxicity of nanomaterials, the advent of ultrasmall nanomagnets as a healthier alternative with superior properties and compatible cellular interactions is reviewed. In summary, these discussions spotlight the versatility and integration of multi-tasking nanomagnets and ultrasmall nanomagnets for diverse cancer theragnostics.
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Blood group analysis has evolved from conventional "test-tube" to ingenious "lab-on-a-chip" micro/paper-fluidic devices for identifying blood phenotypes. Despite the rapid and economical fabrication of these devices, they require Whatman paper that is obtained by cutting down trees and plastic usage involving complex and sophisticated facilities, making scalable manufacturing laborious and expensive. Most importantly, deforestation and plastic incineration pose great threats to the biotic and abiotic environments. Here, we have developed a blood grouping strip utilizing fish-scale waste and household cardboard-waste generated origami as an affordable and sustainable strategy. The naturally inherited hydrophilicity of fish scale with a contact angle of 89° could succinctly auto-stabilize low-volume antisera without the aid of additives. Moreover, unlike paperfluidics, antisera absorption, as well as RBC-antisera agglutination upon blood introduction, happens on the spot with no capillary wicking. The merits of our technique are: it requires a low amount of blood (3 µL), eliminates additional image processing and assays, is equipment-free, and aids accurate blood typing as a visual hemagglutination readout. Additionally, a high tensile strength of â¼85 ± 5 MPa and the shelf-endurance of the bio-disc allowed us to use the simplest cardboard origami as a shield, obviating plastic and fiber generated fancy shields, making our device portable and simultaneously biodegradable. Our novel bio-disc blood analysis was tested with anonymous blood samples (n = 200), with an accuracy comparable to a standard blood group assay. This zero-cost paper, plastic-free eco-friendly blood group analyser derived from biodegradable food and cardboard waste as a resourceful technique has huge potential in various sensors and point-of-care diagnostics, especially in impoverished areas with limited or no lab facilities.
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Antígenos de Grupos Sanguíneos , Sueros Inmunes , Dispositivos Laboratorio en un Chip , Plásticos , Pruebas en el Punto de AtenciónRESUMEN
Cancer therapy is a fast-emerging biomedical paradigm that elevates the diagnostic and therapeutic po-tential of a nanovector for identification,monitoring,targeting,and post-treatment response analysis.Nanovectors of superparamagnetic iron oxide nanoparticles(SPION)are of tremendous significance in cancer therapy because of their inherited high surface area,high reactivity,biocompatibility,superior contrast,and magnetic and photo-inducibility properties.In addition to a brief introduction,we summarize various progressive aspects of nanomagnets pertaining to their production with an emphasis on sustainable biomimetic approaches.Post-synthesis particulate and surface alterations in terms of pharmaco-affinity,liquid accessibility,and biocompatibility to facilitate cancer therapy are highlighted.SPION parameters including particle contrast,core-fusions,surface area,reactivity,photosensitivity,photodynamics,and photothermal properties,which facilitate diverse cancer diagnostics,are discussed.We also elaborate on the concept of magnetism to selectively focus chemotherapeutics on tumors,cell sorting,purification of bio-entities,and elimination of toxins.Finally,while addressing the toxicity of nanomaterials,the advent of ultrasmall nanomagnets as a healthier alternative with superior properties and compatible cellular in-teractions is reviewed.In summary,these discussions spotlight the versatility and integration of multi-tasking nanomagnets and ultrasmall nanomagnets for diverse cancer theragnostics.
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OBJECTIVES: Mechanical ventilation of patients with acute respiratory distress syndrome should balance lung and diaphragm protective principles, which may be difficult to achieve in routine clinical practice. Through a Phase I clinical trial, we sought to determine whether a computerized decision support-based protocol (real-time effort-driven ventilator management) is feasible to implement, results in improved acceptance for lung and diaphragm protective ventilation, and improves clinical outcomes over historical controls. DESIGN: Interventional nonblinded pilot study. SETTING: PICU. PATIENTS: Mechanically ventilated children with acute respiratory distress syndrome. INTERVENTIONS: A computerized decision support tool was tested which prioritized lung-protective management of peak inspiratory pressure-positive end-expiratory pressure, positive end-expiratory pressure/FIO2, and ventilatory rate. Esophageal manometry was used to maintain patient effort in a physiologic range. Protocol acceptance was reported, and enrolled patients were matched 4:1 with respect to age, initial oxygenation index, and percentage of immune compromise to historical control patients for outcome analysis. MEASUREMENTS AND MAIN RESULTS: Thirty-two patients were included. Acceptance of protocol recommendations was over 75%. One-hundred twenty-eight matched historical controls were used for analysis. Compared with historical controls, patients treated with real-time effort-driven ventilator management received lower peak inspiratory pressure-positive end-expiratory pressure and tidal volume, and higher positive end-expiratory pressure when FIO2 was greater than 0.60. Real-time effort-driven ventilator management was associated with 6 more ventilator-free days, shorter duration until the first spontaneous breathing trial and 3 fewer days on mechanical ventilation among survivors (all p ≤ 0.05) in comparison with historical controls, while maintaining no difference in the rate of reintubation. CONCLUSIONS: A computerized decision support-based protocol prioritizing lung-protective ventilation balanced with reduction of controlled ventilation to maintain physiologic levels of patient effort can be implemented and may be associated with shorter duration of ventilation.
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Respiración con Presión Positiva , Respiración Artificial , Niño , Humanos , Proyectos Piloto , Volumen de Ventilación Pulmonar , Ventiladores MecánicosRESUMEN
Lung Protective Mechanical Ventilation (MV) of critically ill adults and children is lifesaving but it may decrease diaphragm contraction and promote Ventilator Induced Diaphragm Dysfunction (VIDD). An ideal MV strategy would balance lung and diaphragm protection. Building off a Phase I pilot study, we are conducting a Phase II controlled clinical trial that seeks to understand the evolution of VIDD in critically ill children and test whether a novel computer-based approach (Real-time Effort Driven ventilator management (REDvent)) can balance lung and diaphragm protective ventilation to reduce time on MV. REDvent systematically adjusts PEEP, FiO2, inspiratory pressure, tidal volume and rate, and uses real-time measures from esophageal manometry to target normal levels of patient effort of breathing. This trial targets 276 children with pulmonary parenchymal disease. Patients are randomized to REDvent vs. usual care for the acute phase of MV (intubation to first Spontaneous Breathing Trial (SBT)). Patients in either group who fail their first SBT will be randomized to REDvent vs usual care for weaning phase management (interval from first SBT to passing SBT). The primary clinical outcome is length of weaning, with several mechanistic outcomes. Upon completion, this study will provide important information on the pathogenesis and timing of VIDD during MV in children and whether this computerized protocol targeting lung and diaphragm protection can lead to improvement in intermediate clinical outcomes. This will form the basis for a larger, Phase III multi-center study, powered for key clinical outcomes such as 28-day ventilator free days. Clinical Trials Registration: NCT03266016.
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Sistemas de Apoyo a Decisiones Clínicas , Diafragma/fisiopatología , Trastornos Respiratorios/prevención & control , Respiración Artificial/métodos , Insuficiencia Respiratoria/terapia , Lesión Pulmonar Inducida por Ventilación Mecánica/prevención & control , Algoritmos , Niño , Preescolar , Ensayos Clínicos Fase II como Asunto , Humanos , Lactante , Pulmón/fisiopatología , Manometría , Terapia por Inhalación de Oxígeno/métodos , Respiración con Presión Positiva/métodos , Ensayos Clínicos Controlados Aleatorios como Asunto , Desconexión del Ventilador/métodosRESUMEN
A generalized method for sorting nanoparticles based on their cores does not exist; it is an immediate necessity, and an approach incorporating cost-effectiveness and biocompatibility is in demand. Therefore, an efficient method for the separation of various mixed core-compositions or dissimilar metallic nanoparticles to their pure forms at the nano-bio interface was developed. Various simple core-combinations of monodispersed nanoparticles with dual cores, including silver plus gold, iron oxide plus gold and platinum plus gold, to the complex three-set core-combinations of platinum plus gold plus silver and platinum plus iron plus gold were sorted using step-gradient centrifugation in a sucrose suspension. Viscosity mediated differential terminal velocities of the nanoparticles permitted diversified dragging at different gradients allowing separation. Stability, purity and properties of the nanoparticles during separation were evaluated based on visual confirmation and by employing advanced instrumentations. Moreover, theoretical studies validated our experimental observations, revealing the roles of various parameters, such as the viscosity of sucrose, the density of the particles and the velocity and duration of centrifugation, involved during the separation process. This remarkably rapid, cost-efficient and sustainable strategy can be adapted to separate other cores of nanoparticles for various biomedical research purposes, primarily to understand nanoparticle induced toxicity and particle fate and transformations in natural biotic environments.
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The first intermolecular ring-expansion cascade of azirines with alkynes for the synthesis of pyridines, enabled by a copper/triethylamine catalytic system via simultaneous generation and utilization of yne-enamine and skipped-yne-imine intermediates, is reported. Experimental as well as computational mechanistic studies revealed that the role of triethylamine is crucial in deciding the reaction pathway toward the pyridine products. This process offers a novel, one-step, direct, and practical strategy for the rapid construction of highly substituted pyridines under exceedingly mild conditions, and an installed alkyne functionality.
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Silver nanoparticle-aided enhancement in the anti-corrosion potential and stability of plant extract as ecologically benign alternative for microbially induced corrosion treatment is demonstrated. Bioengineered silver nanoparticles (AgNPs) surface functionalized with plant extract material (proteinacious) was generated in vitro in a test tube by treating ionic AgNO3 with the leaf extract of Azadirachta indica that acted as dual reducing as well as stabilizing agent. Purity and crystallinity of the AgNPs, along with physical and surface characterizations, were evaluated by performing transmission electron microscopy, Fourier transform infrared spectroscopy, energy dispersive x-ray spectra, single-area electron diffractions, zeta potential, and dynamic light scattering measurements. Anti-corrosion studies against mild steel (MS1010) by corrosion-inducive bacterium, Bacillus thuringiensis EN2 isolated from cooling towers, were evaluated by performing electrochemical impedance spectroscopy (EIS), weight loss analysis, and surface analysis by infrared spectroscopy. Our studies revealed that AgNPs profoundly inhibited the biofilm on MS1010 surface and reduced the corrosion rates with the CR of 0.5 mm/y and an inhibition efficiency of 77% when compared to plant extract alone with a CR of 2.2 mm/y and an inhibition efficiency of 52%. Further surface analysis by infrared spectra revealed that AgNPs formed a protective layer of self-assembled film on the surface of MS1010. Additionally, EIS and surface analysis revealed that the AgNPs have inhibited the bacterial biofilm and reduced the pit on MS1010. This is the first report disclosing the application of bioengineered AgNP formulations as potent anti-corrosive inhibitor upon forming a protective layer over mild steel in cooling water towers. Graphical Abstract á .
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Antibacterianos/química , Bioingeniería/métodos , Nanopartículas del Metal/química , Compuestos de Plata/química , Acero/química , Antibacterianos/síntesis química , Antibacterianos/farmacología , Azadirachta/química , Bacillus thuringiensis/efectos de los fármacos , Bacillus thuringiensis/fisiología , Biopelículas/efectos de los fármacos , Biopelículas/crecimiento & desarrollo , Corrosión , Nanopartículas del Metal/ultraestructura , Extractos Vegetales/química , Extractos Vegetales/farmacologíaRESUMEN
Production of AgNPs with desired morphologies and surface characteristics using facile, economic and non-laborious processes is highly imperative. Cell extract based syntheses are emerging as a novel technique for the production of diverse forms of NPs, and is assured to meet the requirements. Therefore, in order to have a better understanding, and to improvise and gain control over the NPs morphological and surface characteristics, the present investigation systematically evaluates the influence of various major physico-cultural parameters including diverse growth media, concentrations of precursor salts; pH and temperature on the biotransformation of ionic silver (Ag+) to nanopariculate silver nanoparticles (AgNPs), utilizing the cell free extract of the bacterium, P. plecoglossicida. The synthesis, purity, morphology and surface characteristics of the AgNPs during optimization studies were measured. The bactericidal effect of these AgNPs was assessed using multi-drug resistant human pathogens; Acinetobacter baumannii, Escherichia coli, Pseudomonas aeruginosa and Salmonella enterica based on the diameter of inhibition zone in disk diffusion tests. The nanoparticles were found to be of higher toxicity to E. coli and S. enterica than A. baumannii and P. aeruginosa. The results demonstrate that the chosen parameters in whole or in part could have a significant influence on the morphology, surface characteristics, duration of production, overall yield and production of AgNPs.
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Antibacterianos/química , Antibacterianos/farmacología , Nanopartículas del Metal , Plata , Antibacterianos/farmacocinética , Bacterias/efectos de los fármacos , Bacterias/patogenicidad , Farmacorresistencia Bacteriana Múltiple , Humanos , Nanopartículas del Metal/uso terapéutico , Nanopartículas del Metal/ultraestructura , Pruebas de Sensibilidad Microbiana , Pseudomonas/metabolismo , Plata/uso terapéuticoRESUMEN
Immunotherapy is currently being investigated for the treatment of many diseases, including cancer. The ability to control the location of immune cells during or following activation would represent a powerful new technique for this field. Targeted magnetic delivery is emerging as a technique for controlling cell movement and localization. Here we show that this technique can be extended to microglia, the primary phagocytic immune cells in the central nervous system. The magnetized microglia were generated by loading the cells with iron oxide nanoparticles functionalized with CpG oligonucleotides, serving as a proof of principle that nanoparticles can be used to both deliver an immunostimulatory cargo to cells and to control the movement of the cells. The nanoparticle-oligonucleotide conjugates are efficiently internalized, non-toxic, and immunostimulatory. We demonstrate that the in vitro migration of the adherent, loaded microglia can be controlled by an external magnetic field and that magnetically-induced migration is non-cytotoxic. In order to capture video of this magnetically-induced migration of loaded cells, a novel 3D-printed "cell box" was designed to facilitate our imaging application. Analysis of cell movement velocities clearly demonstrate increased cell velocities toward the magnet. These studies represent the initial step towards our final goal of using nanoparticles to both activate immune cells and to control their trafficking within the diseased brain.
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Separación Inmunomagnética/métodos , Nanopartículas de Magnetita/química , Fagocitos/citología , Animales , Línea Celular , Ratones , Microglía , Oligodesoxirribonucleótidos/química , Oligodesoxirribonucleótidos/farmacocinética , Fagocitos/metabolismoRESUMEN
Engineered nanoparticles of diverse forms are being profoundly used for various applications and demand ecologically benign synthesis processes. Conventional chemical methods employed for the syntheses of nanoparticles are environmentally unfriendly and energy intensive. Biologically inspired biofabrication approaches that utilize naturally existing microorganisms or plant extracts or biomaterials might overcome these issues. The present investigation for the first time shows the synthesis of small and monodispersed cadmium selenide nanoparticles utilizing the plant pathogenic fungus, Helminthosporum solani upon incubating with an aqueous solution of CdCl2 and SeCl4 under ambient conditions. Multiple physical characterizations involving ultraviolet-visible and photoluminescence spectroscopy, transmission electron microscopy, selected area electron diffraction and X-ray photoelectron spectroscopy confirmed the production, purity, optical and surface characteristics, crystalline nature, size and shape distributions, and elemental composition of the nanoparticles. Pluralities of the particles are monodisperse spheres with a mean diameter of 5.5±2 nm, are hydrophilic, highly stable with a broad photoluminescence and 1% quantum yield. This approach provides an alternative facile route for the biofabrication of quantum dot that is reliable, environmentally friendly, and lends itself directly for the creation of fluorescent biological labels.
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Compuestos de Cadmio/química , Nanopartículas del Metal/química , Puntos Cuánticos , Compuestos de Selenio/química , Antifúngicos/química , Técnicas Biosensibles , Cloruro de Cadmio/química , Cloruros/química , Electrones , Hongos/metabolismo , Luminiscencia , Microscopía Electrónica de Transmisión , Nanopartículas/química , Nanotecnología , Óptica y Fotónica , Espectroscopía de Fotoelectrones , Rodaminas/química , Espectrofotometría Ultravioleta , Difracción de Rayos XRESUMEN
We report microbially facilitated synthesis of cadmium sulfide (CdS) nanostructured particles (NP) using anaerobic, metal-reducing Thermoanaerobacter sp. The extracellular CdS crystallites were <10 nm in size with yields of ~3 g/L of growth medium/month with demonstrated reproducibility and scalability up to 24 L. During synthesis, Thermoanaerobacter cultures reduced thiosulfate and sulfite salts to H2S, which reacted with Cd²âº cations to produce thermodynamically favored NP in a single step at 65 °C with catalytic nucleation on the cell surfaces. Photoluminescence (PL) analysis of dry CdS NP revealed an exciton-dominated PL peak at 440 nm, having a narrow full width at half maximum of 10 nm. A PL spectrum of CdS NP produced by dissimilatory sulfur reducing bacteria was dominated by features associated with radiative exciton relaxation at the surface. High reproducibility of CdS NP PL features important for scale-up conditions was confirmed from test tubes to 24 L batches at a small fraction of the manufacturing cost associated with conventional inorganic NP production processes.
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Compuestos de Cadmio/metabolismo , Espacio Extracelular/metabolismo , Nanoestructuras/química , Nanoestructuras/economía , Sulfuros/metabolismo , Thermoanaerobacter/metabolismo , Biomasa , Biotecnología , Compuestos de Cadmio/química , Compuestos de Cadmio/economía , Catálisis , Cristalización , Medios de Cultivo , Fermentación , Mediciones Luminiscentes , Nanotecnología , Reproducibilidad de los Resultados , Análisis Espectral , Sulfuros/química , Sulfuros/economía , Sulfitos/metabolismo , Azufre/metabolismo , Tiosulfatos/metabolismo , Factores de TiempoRESUMEN
Naturally existing biological materials have been garning considerable attention as environmentally benign green-nanofactories for the fabrication of diverse nanomaterials, and with desired size and shape distributions. In the present investigation, we report the size and shape controllable biofabrication of silver nanocrystallites using the growth extract of the fungus, Rhizoctonia solani. Influence of various factors such as growth medium; radiation, in the form of sun light; and seeding duration on the production of silver nanoparticles using aqueous 1 mm silver nitrate solution under ambient conditions is presented. Our results demonstrate that these factors can significantly influence the production, size and shape transformation, and the rate of nanoparticles formation. Multiple characterization techniques involving UV-visible and Fourier transform infrared spectroscopy, X-ray diffraction, energy dispersive X-ray spectroscopy and transmission electron microscopy measurements confirmed the production, surface and structural characteristics, purity and crystalline nature of the biosynthesized silver nanoparticles. Our biogenic synthesis process provides a simple, ecologically friendly, cost-effective synthesis route, and most importantly the ability to have control over the size and shape distributions that lends itself for various biomedical and opto-electronic applications.
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Nanoestructuras , Plata/química , Microscopía Electrónica de Transmisión , Espectrometría por Rayos X , Espectrofotometría Ultravioleta , Espectroscopía Infrarroja por Transformada de Fourier , Difracción de Rayos XRESUMEN
Targeted delivery of therapeutic agents to tumor sites increases efficacy and limits off-target toxicity. Nanoparticles are an emerging class of targeted drug delivery systems. Commonly, nanoparticles are coated with poly(ethylene glycol) (PEG) to reduce off-target uptake by cells of the mononuclear phagocyte system (MPS) and a targeting moiety to promote uptake at the desired location. This approach holds great promise, but such constructs still predominantly accumulate in the liver. Here we demonstrate a different approach to tumor targeting using nanoparticles functionalized with a PEG coating that is shed in the presence of matrix metalloproteinase-2 (MMP-2), which is overexpressed in many tumor microenvironments. There was very little uptake of intact particles by human breast adenocarcinoma cells, whereas, when the same cells were treated with particles in the presence of MMP-2, the resulting denuded particles were rapidly taken up by the cells. This system is remarkably simple as the core nanoparticles revealed by PEG cleavage are not modified; uptake is driven simply by revealing the nanoparticle surface. The cleavable linker is a modular component that, in the future, can be designed to respond to other stimuli. This approach could lead to improved imaging and targeted drug delivery for solid tumors.
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Metal and metal oxide nanoparticles are among the most commonly used nanomaterials and their potential for adversely affecting environmental systems raises concern. Complex microbial consortia underlie environmental processes, and the potential toxicity of nanoparticles to microbial systems, and the consequent impacts on trophic balances, is particularly worrisome. The diverse array of metal and metal oxides, the different sizes and shapes that can be prepared and the variety of possible surface coatings complicate assessments of toxicity. Further muddling biocidal interpretations are the diversity of microbes and their intrinsic tolerances to stresses. Here, we review a range of studies focused on nanoparticle-microbial interactions in an effort to correlate the physical-chemical properties of engineered metal and metal oxide nanoparticles to their biological response. General conclusions regarding the parent material of the nanoparticle and the nanoparticle's size and shape on potential toxicity can be made. However, the surface coating of the material, which can be altered significantly by environmental conditions, can ameliorate or promote microbial toxicity. Understanding nanoparticle transformations and how the nanoparticle surface can be designed to control toxicity represents a key area for further study. Additionally, the vast array of microbial species and the structuring of these species within communities complicate extrapolations of nanoparticle toxicity in real world settings. Ultimately, to interpret the effect and eventual fate of engineered materials in the environment, an understanding of the relationship between nanoparticle properties and responses at the molecular, cellular and community levels will be essential.
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Nanopartículas del Metal/química , Metales/química , Nanoestructuras/química , Óxidos/química , Agricultura/métodos , Antiinfecciosos/farmacología , Bacterias/metabolismo , Cadmio/química , Ecosistema , Diseño de Equipo , Oro/química , Ensayo de Materiales , Pruebas de Sensibilidad Microbiana , Microscopía Electrónica de Transmisión/métodos , Nanopartículas/química , Nanotecnología/métodos , Tamaño de la Partícula , Plata/química , Microbiología del SueloRESUMEN
Due to their unique antimicrobial properties silver nanocrystallites have garnered substantial attention and are used extensively for biomedical applications as an additive to wound dressings, surgical instruments and bone substitute materials. They are also released into unintended locations such as the environment or biosphere. Therefore it is imperative to understand the potential interactions, fate and transport of nanoparticles with environmental biotic systems. Numerous factors including the composition, size, shape, surface charge, and capping molecule of nanoparticles are known to influence cell cytotoxicity. Our results demonstrate that the physical/chemical properties of the silver nanoparticles including surface charge, differential binding and aggregation potential, which are influenced by the surface coatings, are a major determining factor in eliciting cytotoxicity and in dictating potential cellular interactions. In the present investigation, silver nanocrystallites with nearly uniform size and shape distribution but with different surface coatings, imparting overall high negativity to high positivity, were synthesized. These nanoparticles included poly(diallyldimethylammonium) chloride-Ag, biogenic-Ag, colloidal-Ag (uncoated), and oleate-Ag with zeta potentials +45 ± 5, -12 ± 2, -42 ± 5, and -45 ± 5 mV, respectively; the particles were purified and thoroughly characterized so as to avoid false cytotoxicity interpretations. A systematic investigation on the cytotoxic effects, cellular response, and membrane damage caused by these four different silver nanoparticles was carried out using multiple toxicity measurements on mouse macrophage (RAW-264.7) and lung epithelial (C-10) cell lines. Our results clearly indicate that the cytotoxicity was dependent on various factors such as surface charge and coating materials used in the synthesis, particle aggregation, and the cell-type for the different silver nanoparticles that were investigated. Poly(diallyldimethylammonium)-coated Ag nanoparticles were found to be the most toxic, followed by biogenic-Ag and oleate-Ag nanoparticles, whereas uncoated or colloidal silver nanoparticles were found to be the least toxic to both macrophage and lung epithelial cells. Also, based on our cytotoxicity interpretations, lung epithelial cells were found to be more resistant to the silver nanoparticles than the macrophage cells, regardless of the surface coating.
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Células Epiteliales/efectos de los fármacos , Macrófagos/efectos de los fármacos , Nanopartículas del Metal/química , Plata/farmacología , Animales , Línea Celular , Relación Dosis-Respuesta a Droga , Ratones , Tamaño de la Partícula , Plata/química , Relación Estructura-Actividad , Propiedades de SuperficieRESUMEN
Interest in engineered metal and semiconductor nanocrystallites continues to grow due to their unique size- and shape-dependent optoelectronic, physicochemical and biological properties. Therefore identifying novel non-hazardous nanoparticle synthesis routes that address hydrophilicity, size and shape control and production costs has become a priority. In the present article we report for the first time on the efficient generation of extracellular silver sulfide (Ag2S) nanoparticles by the metal-reducing bacterium Shewanella oneidensis. The particles are reasonably monodispersed and homogeneously shaped. They are produced under ambient temperatures and pressures at high yield, 85% theoretical maximum. UV-visible and Fourier transform infrared spectroscopy, dynamic light scattering, X-ray diffraction, transmission electron microscopy and X-ray photoelectron spectroscopy measurements confirmed the formation, optical and surface properties, purity and crystallinity of the synthesized particles. Further characterization revealed that the particles consist of spheres with a mean diameter of 9±3.5 nm, and are capped by a detachable protein/peptide surface coat. Toxicity assessments of these biogenic Ag2S nanoparticles on Gram-negative (Escherichia coli and S. oneidensis) and Gram-positive (Bacillus subtilis) bacterial systems, as well as eukaryotic cell lines including mouse lung epithelial (C 10) and macrophage (RAW-264.7) cells, showed that the particles were non-inhibitory and non-cytotoxic to any of these systems. Our results provide a facile, eco-friendly and economical route for the fabrication of technologically important semiconducting Ag2S nanoparticles. These particles are dispersible and biocompatible, thus providing excellent potential for use in optical imaging, electronic devices and solar cell applications.