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1.
Int J Mol Sci ; 22(6)2021 Mar 17.
Artículo en Inglés | MEDLINE | ID: mdl-33802775

RESUMEN

Silver nanoparticles (AgNPs) are the one of the most extensively used nanomaterials. The strong antimicrobial properties of AgNPs have led to their use in a wide range of medical and consumer products. Although the neurotoxicity of AgNPs has been confirmed, the molecular mechanisms have not been extensively studied, particularly in immature organisms. Based on information gained from previous in vitro studies, in the present work, we examine whether ionotropic NMDA glutamate receptors contribute to AgNP-induced neurotoxicity in an animal model of exposure. In brains of immature rats subjected to a low dose of AgNPs, we identified ultrastructural and molecular alterations in the postsynaptic region of synapses where NMDA receptors are localized as a multiprotein complex. We revealed decreased expression of several NMDA receptor complex-related proteins, such as GluN1 and GluN2B subunits, scaffolding proteins PSD95 and SynGAP, as well as neuronal nitric oxide synthase (nNOS). Elucidating the changes in NMDA receptor-mediated molecular mechanisms induced by AgNPs, we also identified downregulation of the GluN2B-PSD95-nNOS-cGMP signaling pathway which maintains LTP/LTD processes underlying learning and memory formation during development. This observation is accompanied by decreased density of NMDA receptors, as assessed by a radioligand binding assay. The observed effects are reversible over the post-exposure time. This investigation reveals that NMDA receptors in immature rats are a target of AgNPs, thereby indicating the potential health hazard for children and infants resulting from the extensive use of products containing AgNPs.


Asunto(s)
Encéfalo/metabolismo , Ácido Glutámico/metabolismo , Nanopartículas del Metal/toxicidad , Receptores de N-Metil-D-Aspartato/metabolismo , Plata/toxicidad , Animales , Encéfalo/efectos de los fármacos , Encéfalo/ultraestructura , GMP Cíclico/metabolismo , Regulación hacia Abajo/efectos de los fármacos , Femenino , Ligandos , Masculino , Nanopartículas del Metal/ultraestructura , Óxido Nítrico/metabolismo , Óxido Nítrico Sintasa de Tipo I/metabolismo , Subunidades de Proteína/metabolismo , Ratas Wistar , Transducción de Señal/efectos de los fármacos , Sinapsis/efectos de los fármacos , Sinapsis/metabolismo , Sinapsis/ultraestructura
2.
Int J Mol Sci ; 22(6)2021 Mar 23.
Artículo en Inglés | MEDLINE | ID: mdl-33806904

RESUMEN

This study was conducted to compare the effects of commercially available (C) and green synthesized (GS) Zinc oxide nanoparticles (ZnO-NPs) on immunological responses of common carp (Cyprinus carpio) skin mucus. GS ZnO-NPs were generated using Thymus pubescent and characterized by UV-vis diffuse reflectance spectroscopy (DRS), Fourier-transform infrared spectroscopy (FTIR), X-ray powder diffraction (XRD), scanning electron microscope (SEM), and energy-dispersive X-ray spectroscopy (EDX). Fish (n = 150) were randomly allocated into five groups in triplicate and received a waterborne concentration of 0% (control), 25%, and 50% of LC50 96 h of commercially available (C1 and C2) and green synthesized ZnO-NPs (GS1 and GS2) for 21 days. Results from XRD displayed ZnO-NPs with 58 nm in size and UV-vis DRS, EDX, and FT-IR analysis showed that some functional groups from plant extract bonded to the surface of NPs. The SEM images showed that ZnO-NPs have conical morphology. Acute toxicity study showed a higher dose of LC5096h for green synthesized ZnO-NPs (78.9 mg.L-1) compared to the commercial source (59.95 mg.L-1). The highest activity of lysozyme and alternative complement activity (ACH50) were found in control and GS1 groups. A significant decrease in alkaline phosphatase activity (ALP) was found in C1 and C2 groups compared to other treatments. Protease activity (P) was significantly decreased in the C2 group compared to the control and GS groups. Total immunoglobulin (total Ig) content was the highest in the control. In addition, total Ig in the GS1 group was higher than GS2. The exposure to ZnO-NPs lowered total protein content in all experimental groups when compared to control. Present findings revealed lower induced immunosuppressive effects by green synthesized ZnO-NPs on key parameters of fish skin mucus.


Asunto(s)
Carpas/fisiología , Factores Inmunológicos/síntesis química , Factores Inmunológicos/farmacología , Nanopartículas del Metal/química , Moco/metabolismo , Piel/efectos de los fármacos , Piel/metabolismo , Óxido de Zinc/química , Animales , Técnicas de Química Sintética , Tecnología Química Verde , Nanopartículas del Metal/ultraestructura , Análisis Espectral
3.
Nat Commun ; 12(1): 2025, 2021 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-33795690

RESUMEN

Circular dichroism (CD) has long been used to trace chiral molecular states and changes of protein configurations. In recent years, chiral plasmonic nanostructures have shown potential for applications ranging from pathogen sensing to novel optical materials. The plasmonic coupling of the individual elements of such metallic structures is a crucial prerequisite to obtain sizeable CD signals. We here identify and implement various coupling entities-chiral and achiral-to demonstrate chiral transfer over distances close to 100 nm. The coupling is realized by an achiral nanosphere situated between a pair of gold nanorods that are arranged far apart but in a chiral fashion using DNA origami. The transmitter particle causes a strong enhancement of the CD response, the emergence of an additional chiral feature at the resonance frequency of the nanosphere, and a redshift of the longitudinal plasmonic resonance frequency of the nanorods. Matching numerical simulations elucidate the intricate chiral optical fields in complex architectures.


Asunto(s)
Dicroismo Circular/métodos , ADN/química , Oro/química , Nanotubos/química , ADN/genética , ADN/ultraestructura , Nanopartículas del Metal/química , Nanopartículas del Metal/ultraestructura , Microscopía Electrónica de Transmisión , Nanoestructuras/química , Nanoestructuras/ultraestructura , Estereoisomerismo
4.
Int J Mol Sci ; 22(4)2021 Feb 14.
Artículo en Inglés | MEDLINE | ID: mdl-33672995

RESUMEN

Multidrug-resistant (MDR) bacteria constitute a global health issue. Over the past ten years, interest in nanoparticles, particularly metallic ones, has grown as potential antibacterial candidates. However, as there is no consensus about the procedure to characterize the metallic nanoparticles (MNPs; i.e., metallic aggregates) and evaluate their antibacterial activity, it is impossible to conclude about their real effectiveness as a new antibacterial agent. To give part of the answer to this question, 12 nm gold and silver nanoparticles have been prepared by a chemical approach. After their characterization by transmission electronic microscopy (TEM), Dynamic Light Scattering (DLS), and UltraViolet-visible (UV-vis) spectroscopy, their surface accessibility was tested through the catalytic reduction of the 4-nitrophenol, and their stability in bacterial culture medium was studied. Finally, the antibacterial activities of 12 nm gold and silver nanoparticles facing Staphylococcus aureus and Escherichia coli have been evaluated using the broth microdilution method. The results show that gold nanoparticles have a weak antibacterial activity (i.e., slight inhibition of bacterial growth) against the two bacteria tested. In contrast, silver nanoparticles have no activity on S. aureus but demonstrate a high antibacterial activity against Escherichia coli, with a minimum inhibitory concentration of 128 µmol/L. This high antibacterial activity is also maintained against two MDR-E. coli strains.


Asunto(s)
Antibacterianos/toxicidad , Escherichia coli/efectos de los fármacos , Oro/química , Nanopartículas del Metal/toxicidad , Plata/química , Staphylococcus aureus/efectos de los fármacos , Antibacterianos/química , Farmacorresistencia Bacteriana Múltiple/efectos de los fármacos , Dispersión Dinámica de Luz , Escherichia coli/crecimiento & desarrollo , Nanopartículas del Metal/química , Nanopartículas del Metal/ultraestructura , Pruebas de Sensibilidad Microbiana/métodos , Microscopía Electrónica de Transmisión , Espectrofotometría , Staphylococcus aureus/crecimiento & desarrollo
5.
J Chromatogr A ; 1642: 462022, 2021 Apr 12.
Artículo en Inglés | MEDLINE | ID: mdl-33714080

RESUMEN

Aureobasidium pullulans was grown in liquid culture media amended with selenite and tellurite and selenium (Se) and tellurium (Te) nanoparticles (NPs) were recovered after 30 d incubation. A separation method was applied to recover and characterise Se and Te NPs by asymmetric flow field flow fractionation (AF4) with online coupling to multi-angle light scattering (MALS), ultraviolet visible spectroscopy (UV-Vis), and inductively coupled plasma mass spectrometry (ICP-MS) detectors. Additional characterisation data was obtained from transmission electron microscopy (TEM), and dynamic light scattering (DLS). Solutions of 0.2% Novachem surfactant and 10 mM phosphate buffer were compared as mobile phases to investigate optimal AF4 separation and particle recovery using Se-NP as a model sample. 88% recovery was reported for 0.2% Novachem solution, compared with 50% recovery for phosphate buffer. Different crossflow (Cflow) rates were compared to further investigate optimum separation, with recoveries of 88% and 30% for Se-NPs, and 90% and 29% for Te-NPs for 3.5 mL min-1 and 2.5 mL min-1 respectively. Zeta-potential (ZP) data suggested higher stability for NP elution in Novachem solution, with increased stability attributed to minimised NP-membrane interaction due to PEGylation. Detection with MALS showed monodisperse Se-NPs (45-90 nm) and polydisperse Te-NPs (5-65 nm).Single particle ICP-MS showed mean particle diameters of 49.7 ±â€¯2.7 nm, and 135 ±â€¯4.3 nm, and limit of size detection (LOSD) of 20 nm and 45 nm for Se-NPs and Te-NPs respectively. TEM images of Se-NPs and Te-NPs displayed a spherical morphology, with the Te-NPs showing a clustered arrangement, which suggested electrostatic attraction amongst neighbouring particles. Particle hydrodynamic diameters (dH) measured with dynamic light scattering (DLS) further suggested monodisperse Se-NPs and polydisperse Te-NPs distributions, showing good agreement with AF4-MALS for Se-NPs, but suggests that the Rg obtained from AF4-MALS for Te-NP was unreliable. The results demonstrate a complementary application of asymmetric flow field-flow fractionation (AF4), ICP-MS, light scattering, UV-Vis detection, and microscopic techniques to characterise biogenic Se and Te NPs.


Asunto(s)
/química , Nanopartículas del Metal/análisis , Selenio/análisis , Telurio/análisis , Dispersión Dinámica de Luz , Fraccionamiento de Campo-Flujo , Nanopartículas del Metal/ultraestructura , Tamaño de la Partícula , Espectrofotometría Atómica , Electricidad Estática , Factores de Tiempo
6.
J Vis Exp ; (168)2021 02 17.
Artículo en Inglés | MEDLINE | ID: mdl-33682852

RESUMEN

Temperature control is a recent development that provides an additional degree of freedom to study nanochemistry by liquid cell transmission electron microscopy. In this paper, we describe how to prepare an in situ heating experiment for studying the effect of temperature on the formation of gold nanoparticles driven by radiolysis in water. The protocol of the experiment is fairly simple involving a special liquid cell with uniform heating capabilities up to 100 °C, a liquid-cell TEM holder with flow capabilities and an integrated interface for controlling the temperature. We show that the nucleation and growth mechanisms of gold nanoparticles are drastically impacted by the temperature in liquid cell. Using STEM imaging and nanodiffraction, the evolution of the density, size, shape and atomic structure of the growing nanoparticles are revealed in real time. Automated image processing algorithms are exploited to extract useful quantitative data from video sequences, such as the nucleation and growth rates of nanoparticles. This approach provides new inputs for understanding the complex physico-chemical processes at play during the liquid-phase synthesis of nanomaterials.


Asunto(s)
Nanopartículas del Metal/química , Nanopartículas del Metal/ultraestructura , Microscopía Electrónica de Transmisión , Temperatura , Oro/química , Calefacción , Procesamiento de Imagen Asistido por Computador , Programas Informáticos , Agua/química
7.
Int J Nanomedicine ; 16: 2187-2201, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33758506

RESUMEN

The physicochemical and optical properties of silver nanoparticles (SNPs) and gold nanoparticles (GNPs) have allowed them to be employed for various biomedical applications, including delivery, therapy, imaging, and as theranostic agents. However, since they are foreign body systems, they are usually redistributed and accumulated in some vital organs, which can produce toxic effects; therefore, this a crucial issue that should be considered for potential clinical trials. This review aimed to summarize the reports from the past ten years that have used SNPs and GNPs for in vivo studies on the diagnosis and treatment of brain diseases and those related to the central nervous system, emphasizing their toxicity as a crucial topic address. The article focuses on the effect of the nanoparticle´s size and chemical composition as relevant parameters for in vivo toxicity. At the beginning of this review, the general toxicity and distribution studies are discussed separately for SNPs and GNPs. Subsequently, this manuscript analyzes the principal applications of both kinds of nanoparticles for glioma, neurodegenerative, and other brain diseases, and discusses the advances in clinical trials. Finally, we analyze research prospects towards clinical applications for both types of metallic nanoparticles.


Asunto(s)
Enfermedades del Sistema Nervioso Central/patología , Oro/química , Nanopartículas del Metal/química , Nanopartículas del Metal/toxicidad , Tamaño de la Partícula , Plata/química , Pruebas de Toxicidad , Animales , Humanos , Nanopartículas del Metal/ultraestructura , Distribución Tisular/efectos de los fármacos
8.
Molecules ; 26(4)2021 Feb 14.
Artículo en Inglés | MEDLINE | ID: mdl-33672903

RESUMEN

Burkholderia pseudomallei is the causative pathogen of melioidosis and this bacterium is resistant to several antibiotics. Silver nanoparticles (AgNPs) are an interesting agent to develop to solve this bacterial resistance. Here, we characterize and assess the antimelioidosis activity of AgNPs against these pathogenic bacteria. AgNPs were characterized and displayed a maximum absorption band at 420 nm with a spherical shape, being well-monodispersed and having high stability in solution. The average size of AgNPs is 7.99 ± 1.46 nm. The antibacterial efficacy of AgNPs was evaluated by broth microdilution. The bactericidal effect of AgNPs was further assessed by time-kill kinetics assay. Moreover, the effect of AgNPs on the inhibition of the established biofilm was investigated by the crystal violet method. In parallel, a study of the resistance induction development of B. pseudomallei towards AgNPs with efflux pump inhibiting effect was performed. We first found that AgNPs had strong antibacterial activity against both susceptible and ceftazidime-resistant (CAZ-resistant) strains, as well as being efficiently active against B. pseudomallei CAZ-resistant strains with a fast-killing mode via a bactericidal effect within 30 min. These AgNPs did not only kill planktonic bacteria in broth conditions, but also in established biofilm. Our findings first documented that the resistance development was not induced in B. pseudomallei toward AgNPs in the 30th passage. We found that AgNPs still showed an effective efflux pump inhibiting effect against these bacteria after prolonged exposure to AgNPs at sublethal concentrations. Thus, AgNPs have valuable properties for being a potent antimicrobial agent to solve the antibiotic resistance problem in pathogens.


Asunto(s)
Proteínas Bacterianas/antagonistas & inhibidores , Burkholderia pseudomallei/fisiología , Melioidosis/tratamiento farmacológico , Melioidosis/microbiología , Nanopartículas del Metal/uso terapéutico , Plata/uso terapéutico , Taninos/uso terapéutico , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Proteínas Bacterianas/metabolismo , Burkholderia pseudomallei/efectos de los fármacos , Ceftazidima/farmacología , Ceftazidima/uso terapéutico , Farmacorresistencia Bacteriana/efectos de los fármacos , Dispersión Dinámica de Luz , Cinética , Nanopartículas del Metal/ultraestructura , Pruebas de Sensibilidad Microbiana , Viabilidad Microbiana/efectos de los fármacos , Fenotipo , Plata/farmacología , Electricidad Estática , Taninos/farmacología
9.
Int J Nanomedicine ; 16: 1757-1773, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33688190

RESUMEN

Background: NiO nanoparticles have attracted much attention due to their unique properties. They have been synthesized using chemical and physical techniques that often need toxic chemicals. These toxic chemicals cannot easily be removed from the nanoparticle's surface, make them less biocompatible, and limit their biological applications. Instead, plants based green synthesis of nanoparticles uses phytomolecules as reducing and capping agents. These phytomolecules are biologically active with no or less toxic effects. Materials and Methods: Phytomolecules-coated NiO nanoparticles were synthesized employing a green route using Abutilon indicum leaf extract. For comparative study, we also have synthesized NiO nanoparticles using the co-precipitation method. Synthesized nanoparticles were successfully characterized using different spectroscopic techniques. The synthesized nanoparticles were evaluated for antibacterial activity with agar well diffusion assay against different bacteria compared to standard drug and plant extract. They are also examined for anticancer potential using MTT assay against HeLa cancer cells, and further, their antioxidant potential was determined using DPPH assay. Biocompatibility of the synthesized nanoparticles was assessed against fibroblast cells. Results: Phytomolecules-coated NiO nanoparticles were demonstrated superior antibacterial and anticancer performance against bacteria (E. coli, B. bronchiseptica, B. subtilis, and S. aureus) by presenting highest zone of inhibitions (18 ± 0.58 mm, 21 ± 0.45 mm, 22 ± 0.32 mm, and 23 ± 0.77 mm) and HeLa cancer cells by exhibiting the least cell viability percentage (51.74 ± 0.35%) compared to plant extract and chemically synthesized NiO nanoparticles but were comparable to standard antibiotic and anticancer drugs, respectively. Phytomolecules-coated NiO nanoparticles were also demonstrated excellent antioxidant activity (79.87 ± 0.43% DPPH inhibition) and biocompatibility (> 90% cell viability) with fibroblast cells. Conclusion: Nanoparticle synthesis using the Abutilon indicum leaf extract is an efficient and economical method, produces biocompatible and more biologically active nanoparticles, which can be an excellent candidate for therapeutic applications.


Asunto(s)
Antiinfecciosos/farmacología , Antineoplásicos/farmacología , Antioxidantes/farmacología , Malvaceae/química , Nanopartículas del Metal/química , Fitoquímicos/química , Extractos Vegetales/química , Hojas de la Planta/química , Bacterias/efectos de los fármacos , Compuestos de Bifenilo/química , Fibroblastos/efectos de los fármacos , Tecnología Química Verde , Células HeLa , Humanos , Peroxidación de Lípido/efectos de los fármacos , Masculino , Nanopartículas del Metal/ultraestructura , Pruebas de Sensibilidad Microbiana , Picratos/química , Espectrometría por Rayos X , Espectrofotometría Ultravioleta , Espectroscopía Infrarroja por Transformada de Fourier , Electricidad Estática , Difracción de Rayos X
10.
Int J Nanomedicine ; 16: 1901-1911, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33707945

RESUMEN

Purpose: Developing a sensitive SERS-based method to quantitatively detect serum biomarkers (Aß1-42 and P-Tau-181) for the early diagnosis of Alzheimer's disease (AD). Methods: In this study, a novel SERS-based sandwich immunoassay, which consists of tannin-capped silver nanoparticles and magnetic graphene oxide (Fe3O4@GOs), was developed. We firstly applied this method for the detection of protein standards in buffer solution, obtaining the regression equation. Then, its potential value on real serum samples of AD was further explored. Results: The detection linear range of Aß1-42 and P-Tau-181 protein standards were observed to range from 100 pg mL-1 to 10 fg mL-1, 100 pg mL-1 to 1 fg mL-1 respectively. We finally explored clinical application of the proposed method in 63 serum samples. As a result, P-tau-181 differentiated AD from non-AD dementia patients (AUC = 0.770), with a more favored ROC than Aß1-42 (AUC = 0.383). Conclusion: The developed SERS-based immunoassay is successfully applied to the determination of Aß1-42 and P-Tau-181 in human serum specimens, which provides a promising tool for the early diagnosis of AD.


Asunto(s)
Enfermedad de Alzheimer/sangre , Enfermedad de Alzheimer/diagnóstico , Biomarcadores/sangre , Inmunoensayo/métodos , Sondas Moleculares/química , Plata/química , Espectrometría Raman/métodos , Péptidos beta-Amiloides/sangre , Benzoatos/química , Calibración , Femenino , Grafito/química , Humanos , Límite de Detección , Masculino , Nanopartículas del Metal/química , Nanopartículas del Metal/ultraestructura , Compuestos de Sulfhidrilo/química , Difracción de Rayos X , Proteínas tau/sangre
11.
Int J Nanomedicine ; 16: 1993-2011, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33727811

RESUMEN

Background: Even with considerable improvement in treatment of epithelial ovarian cancer achieved in recent years, an increasing chemotherapy resistance and disease 5-year relapse is recorded for a majority part of patients that encourages the search for better therapeutic options. Gold nanoparticles (Au NPs) due to plethora of unique physiochemical features are thoroughly tested as drug delivery, radiosensitizers, as well as photothermal and photodynamic therapy agents. Importantly, due to highly controlled synthesis, it is possible to obtain nanomaterials with directed size and shape. Methods: In this work, we developed novel elongated-type gold nanoparticles in the shape of nanopeanuts (AuP NPs) and investigated their cytotoxic potential against ovarian cancer cells SKOV-3 using colorimetric and fluorimetric methods, Western blot, flow cytometry, and fluorescence microscopy. Results: Peanut-shaped gold nanoparticles showed high anti-cancer activity in vitro against SKOV-3 cells at doses of 1-5 ng/mL upon 72 hours treatment. We demonstrate that AuP NPs decrease the viability and proliferation capability of ovarian cancer cells by triggering cell apoptosis and autophagy, as evidenced by flow cytometry and Western blot analyses. The overproduction of reactive oxygen species (ROS) was noted to be a critical mediator of AuP NPs-mediated cell death. Conclusion: These data indicate that gold nanopeanuts might be developed as nanotherapeutics against ovarian cancer.


Asunto(s)
Apoptosis , Autofagia , Oro/química , Nanopartículas del Metal/química , Neoplasias Ováricas/patología , Especies Reactivas de Oxígeno/metabolismo , Apoptosis/efectos de los fármacos , Proteínas Reguladoras de la Apoptosis/metabolismo , Arachis , Autofagia/efectos de los fármacos , Carcinoma Epitelial de Ovario/tratamiento farmacológico , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Femenino , Humanos , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Nanopartículas del Metal/toxicidad , Nanopartículas del Metal/ultraestructura , Neoplasias Ováricas/tratamiento farmacológico , Oxidación-Reducción
12.
Int J Nanomedicine ; 16: 2071-2085, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33727814

RESUMEN

Background: Radiation therapy remains an important treatment modality in cancer therapy, however, resistance is a major problem for treatment failure. Elevated expression of glutathione is known to associate with radiation resistance. We used glutathione overexpressing small cell lung cancer cell lines, SR3A-13 and SR3A-14, established by transfection with γ-glutamylcysteine synthetase (γ-GCS) cDNA, as a model for investigating strategies of overcoming radiation resistance. These radiation-resistant cells exhibit upregulated human copper transporter 1 (hCtr1), which also transports cisplatin. This study was initiated to investigate the effect and the underlying mechanism of iron-platinum nanoparticles (FePt NPs) on radiation sensitization in cancer cells. Materials and Methods: Uptakes of FePt NPs in these cells were studied by plasma optical emission spectrometry and transmission electron microscopy. Effects of the combination of FePt NPs and ionizing radiation were investigated by colony formation assay and animal experiment. Intracellular reactive oxygen species (ROS) were assessed by using fluorescent probes and imaged by a fluorescence-activated-cell-sorting caliber flow cytometer. Oxygen consumption rate (OCR) in mitochondria after FePt NP and IR treatment was investigated by a Seahorse XF24 cell energy metabolism analyzer. Results: These hCtr1-overexpressing cells exhibited elevated resistance to IR and the resistance could be overcome by FePt NPs via enhanced uptake of FePt NPs. Overexpression of hCtr1 was responsible for the increased uptake/transport of FePt NPs as demonstrated by using hCtr1-transfected parental SR3A (SR3A-hCtr1-WT) cells. Increased ROS and drastic mitochondrial damages with substantial reduction of oxygen consumption rate were observed in FePt NPs and IR-treated cells, indicating that structural and functional insults of mitochondria are the lethal mechanism of FePt NPs. Furthermore, FePt NPs also increased the efficacy of radiotherapy in mice bearing SR3A-hCtr1-WT-xenograft tumors. Conclusion: These results suggest that FePt NPs can potentially be a novel strategy to improve radiotherapeutic efficacy in hCtr1-overexpressing cancer cells via enhanced uptake and mitochondria targeting.


Asunto(s)
Aleaciones/farmacología , Transportador de Cobre 1/metabolismo , Hierro/farmacología , Nanopartículas del Metal/química , Mitocondrias/metabolismo , Neoplasias/metabolismo , Platino (Metal)/farmacología , Tolerancia a Radiación , Aerobiosis , Animales , Línea Celular Tumoral , Respiración de la Célula/efectos de los fármacos , Glutatión/metabolismo , Humanos , Nanopartículas del Metal/ultraestructura , Ratones SCID , Mitocondrias/efectos de los fármacos , Mitocondrias/ultraestructura , Modelos Biológicos , Tolerancia a Radiación/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Resultado del Tratamiento , Rayos X
13.
Int J Mol Sci ; 22(4)2021 Feb 10.
Artículo en Inglés | MEDLINE | ID: mdl-33578653

RESUMEN

We present a template-assisted method for synthesizing nanogap shell structures for biomolecular detections based on surface-enhanced Raman scattering. The interior nanogap-containing a silver shell structure, referred to as a silver nanogap shell (Ag NGS), was fabricated on silver nanoparticles (Ag NPs)-coated silica, by adsorbing small aromatic thiol molecules on the Ag NPs. The Ag NGSs showed a high enhancement factor and good signal uniformity, using 785-nm excitation. We performed in vitro immunoassays using a prostate-specific antigen as a model cancer biomarker with a detection limit of 2 pg/mL. To demonstrate the versatility of Ag NGS nanoprobes, extracellular duplex surface-enhanced Raman scattering (SERS) imaging was also performed to evaluate the co-expression of cancer biomarkers, human epidermal growth factor-2 (HER2) and epidermal growth factor receptor (EGFR), in a non-small cell lung cancer cell line (H522). Developing highly sensitive Ag NGS nanoprobes that enable multiplex biomolecular detection and imaging can open up new possibilities for point-of-care diagnostics and provide appropriate treatment options and prognosis.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/diagnóstico , Neoplasias Pulmonares/diagnóstico , Nanopartículas del Metal/química , Receptor ErbB-2/análisis , Plata/química , Biomarcadores de Tumor/análisis , Línea Celular Tumoral , Receptores ErbB/análisis , Humanos , Nanopartículas del Metal/ultraestructura , Espectrometría Raman/métodos
14.
Int J Nanomedicine ; 16: 1345-1360, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33633450

RESUMEN

Purpose: Despite the extensive development of antibacterial biomaterials, there are few reports on the effects of materials on the antibacterial ability of the immune system, and in particular of neutrophils. In this study, we observe differences between the in vivo and in vitro anti-infective efficacies of silver nanoparticles (AgNPs). The present study was designed to further explore the mechanism for this inconsistency using ex vivo models and in vitro experiments. Methods: AgNPs were synthesized using the polyol process and characterized by transmission electron microscopy and X-ray photoelectron spectroscopy. The antibacterial ability of AgNPs and neutrophils was tested by the spread-plate method. The infected air pouch model was prepared to detect the antimicrobial ability of AgNPs in vivo. Furthermore, blood-AgNPs-bacteria co-culture model and reactive oxygen species (ROS) measurement were used to evaluate the effect of AgNPs to neutrophil-mediated phagocytosis and ROS production. Results: The antibacterial experiments in vitro showed that AgNPs had superior antibacterial properties in cell compatible concentration. While, AgNPs had no significant antibacterial effect in vivo, and pathological section in AgNPs group indicated less neutrophil infiltration in inflammatory site than S. aureus group. Furthermore, AgNPs were found to reduce the phagocytosis of neutrophils and inhibit their ability to produce ROS and superoxide during ex vivo and in vitro experiments. Conclusion: This study selects AgNPs as the representative of inorganic nano-biomaterials and reveals the phenomenon and the mechanism underlying the significant AgNPs-induced inhibition of the antibacterial ability of neutrophils, and may have a certain enlightening effect on the development of biomaterials in the future. In the fabrication of antibacterial biomaterials, however, attention should be paid to both cell and immune system safety to make the antibacterial properties of the biomaterials and innate immune system complement each other and jointly promote the host's ability to resist the invasion of pathogenic microorganisms.


Asunto(s)
Antibacterianos/farmacología , Sistema Inmunológico/efectos de los fármacos , Inmunidad Innata/efectos de los fármacos , Nanopartículas del Metal/química , Neutrófilos/citología , Fagocitosis/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Plata/farmacología , Animales , Movimiento Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Modelos Animales de Enfermedad , Femenino , Humanos , Mediadores de Inflamación/metabolismo , Nanopartículas del Metal/ultraestructura , Pruebas de Sensibilidad Microbiana , Neutrófilos/efectos de los fármacos , ARN/metabolismo , Ratas Sprague-Dawley , Staphylococcus aureus/efectos de los fármacos , Superóxidos/metabolismo
15.
Int J Nanomedicine ; 16: 515-538, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33519199

RESUMEN

Background: Several studies have demonstrated various molecular mechanisms involved in the biogenesis and release of exosomes. However, how external stimuli, such as platinum nanoparticles (PtNPs), induces the biogenesis and release of exosomes remains unclear. To address this, PtNPs were synthesized using lutein to examine their effect on the biogenesis and release of exosomes in human lung epithelial adenocarcinoma cancer cells (A549). Methods: The size and concentration of isolated exosomes were characterized by dynamic light scattering (DLS) and nanoparticle tracking analysis system (NTA). Morphology and structure of exosomes were examined using scanning electron microscopy and transmission electron microscopy (TEM), respectively. Quantification of exosomes were analyzed by EXOCETTM assay and fluorescence polarization (FP). The expression of typical markers of exosomes were analyzed by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA). Results: A549 cells cultured with PtNPs enhance exosome secretion by altering various physiological processes. Interestingly, A549 cells treated with PtNPs increases total protein concentration, biogenesis and release of exosomes associated with PtNPs-induced oxidative stress. GW4869 inhibits PtNPs induced biogenesis and release of exosomes and also acetylcholinesterase (AChE), neutral sphingomyelinase activity (n-SMase), and exosome counts. A549 cells pre-treated with N-acetylcysteine (NAC) significantly inhibited PtNPs induced exosome biogenesis and release. These findings confirmed that PtNPs-induced exosome release was due to the induction of oxidative stress and the ceramide pathway. These factors enhanced exosome biogenesis and release and may be useful in understanding the mechanism of exosome formation, release, and function. Conclusion: PtNPs provide a promising agent to increase exosome production in A549 cells. These findings offer novel strategies for enhancing exosome release, which can be applied in the treatment and prevention of cancer. Importantly, this is the first study, to our knowledge, showing that PtNPs stimulate exosome biogenesis by inducing oxidative stress and the ceramide pathway.


Asunto(s)
Adenocarcinoma del Pulmón/metabolismo , Ceramidas/metabolismo , Exosomas/metabolismo , Neoplasias Pulmonares/metabolismo , Nanopartículas del Metal/química , Estrés Oxidativo , Platino (Metal)/farmacología , Células A549 , Acetilcolinesterasa/metabolismo , Acetilcisteína/farmacología , Adenocarcinoma del Pulmón/genética , Adenocarcinoma del Pulmón/patología , Compuestos de Anilina/farmacología , Compuestos de Bencilideno/farmacología , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Activación Enzimática/efectos de los fármacos , Exosomas/ultraestructura , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Luteína/farmacología , Nanopartículas del Metal/ultraestructura , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Estrés Oxidativo/efectos de los fármacos , Tamaño de la Partícula , ARN Mensajero/genética , ARN Mensajero/metabolismo , Suero , Esfingomielina Fosfodiesterasa/metabolismo , Electricidad Estática
16.
Int J Nanomedicine ; 16: 851-865, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33574666

RESUMEN

Background: Ionizing radiation (IR) is commonly used in triple-negative breast cancer (TNBC) treatment regimens. However, off-target toxicity affecting normal tissue and grueling treatment regimens remain major limitations. Hyperthermia is one of the greatest IR sensitizers, but only if heat is administered simultaneously or immediately prior to ionizing radiation. Difficulty in co-localizing ionizing radiation (IR) in rapid succession with hyperthermia, and confining treatment to the tumor have hindered widespread clinical adoption of combined thermoradiation treatment. Metal nanoparticle-based approaches to IR sensitization and photothermal heat generation may aid in overcoming these issues and improve treatment specificity. Methods: We assessed the potential to selectively treat MDA-MB-231 TNBC cells without affecting non-malignant MCF-10A breast cells using a multimodal approach based upon combined photothermal therapy, IR sensitization, and specific cytotoxicity using triangular silver nanoparticles (TAgNPs) with peak absorbance in the near-infrared light (NIR) spectrum. Results: We found that TAgNP-mediated photothermal therapy and radiosensitization offer a high degree of specificity for treatment of TNBC without affecting non-malignant mammary epithelial cells. Discussion: If given at a high enough dose, IR, heat, or TAgNPs alone could be sufficient for tumor treatment. However, when the dose of one or all of these modalities increases, off-target effects also increase. The challenge lies in identifying the minimal doses of each individual treatment such that when combined they provide maximum selectivity for treatment of TNBC cells with minimum off-target effects on non-malignant breast cells. Our results provide proof of concept that this combination is highly selective for TNBC cells while sparing non-malignant mammary epithelial cells. This treatment would be particularly important for patients undergoing breast conservation therapy and for treatment of invasive tumor margins near the periphery where each individual treatment might be at a sub-therapeutic level.


Asunto(s)
Nanopartículas del Metal/uso terapéutico , Radiación Ionizante , Plata/uso terapéutico , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Neoplasias de la Mama Triple Negativas/radioterapia , Animales , Apoptosis/efectos de los fármacos , Apoptosis/efectos de la radiación , Carcinogénesis/efectos de los fármacos , Carcinogénesis/patología , Carcinogénesis/efectos de la radiación , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/efectos de la radiación , Terapia Combinada , Femenino , Humanos , Rayos Infrarrojos , Nanopartículas del Metal/ultraestructura , Fármacos Sensibilizantes a Radiaciones/farmacología , Fármacos Sensibilizantes a Radiaciones/uso terapéutico , Plata/farmacología , Neoplasias de la Mama Triple Negativas/patología
17.
Int J Nanomedicine ; 16: 941-950, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33603361

RESUMEN

Purpose: Candidemia infection is common in the clinic and has a high mortality rate. Candida albicans, Candida tropicalis, and Candida krusei are very important and common pathogenic species. Candida is difficult to isolate from clinical samples and culture, and immunological detection cannot distinguish these related strains. Furthermore, Candida has a complex cell wall, which causes difficulties in the extraction of DNA for nucleic acid detection. The purpose of this study was to establish a protocol for the direct identification of Candida from serum. Materials and Methods: We synthesized Fe3O4@PEI (where PEI stands for polyethylenimine) magnetic nanoparticles to capture Candida and prepared positively charged silver nanoparticles (AgNPs+) as the substrate for surface-enhanced Raman scattering (SERS). Candida was directly identified from serum by SERS detection. Results: Orthogonal partial least squares discriminant analysis (OPLS-DA) was used as the multivariate analysis tool. Principal component analysis confirmed that this method can clearly distinguish common Candida. After 10-fold cross-validation, the accuracy of training data in this model was 100% and the accuracy of test data was 99.8%, indicating that the model has good classification ability. Conclusion: The detection could be completed within 40 minutes using Fe3O4@PEI and AgNPs+ prepared in advance. This is the first time that Fe3O4@PEI was used in the detection of Candida by SERS. We report the first rapid method to identify fungi directly from serum without breaking the cell wall to extract DNA from the fungi.


Asunto(s)
Candida/aislamiento & purificación , Nanopartículas de Magnetita/química , Nanopartículas del Metal/química , Plata/química , Espectrometría Raman/métodos , Candida albicans , Análisis Discriminante , Humanos , Análisis de los Mínimos Cuadrados , Nanopartículas de Magnetita/ultraestructura , Nanopartículas del Metal/ultraestructura , Análisis Multivariante , Polietileneimina/química
18.
Int J Nanomedicine ; 16: 753-761, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33568905

RESUMEN

Purpose: Biomimetic approaches for the synthesis of silver nanoparticles (AgNPs) had created a substantial impression among the research community that focuses on nano-bio interactions. In this study, an eco-friendly method using Rhizophora apiculata aqueous leaf extract as a reductant-rich hydrosol was followed to synthesize AgNPs and test its cytotoxicity. Methods: To optimise the parameters for the synthesis of AgNPs, central composite design based on response surface methodology was used. The particles synthesized at a nano-scale were characterized in our previously published report. The present report further characterizes the nanoparticles by X-ray diffraction, SEM and TEM at varying sites and magnifications. The characterized AgNPs were tested for their cytotoxic effects on HEK-293 and HeLa cells. Results: The cytotoxicity on the cell lines was dose-dependent. At a concentration of 2.5 µL/mL of the AgNPs-containing hydrosol, 100% inhibition of HEK-293 cells and 75% inhibition of the HeLa cells were observed. The IC50 value for AgNPs on HEK-293 was 0.622 µL/mL (12.135 ng), whereas, for HeLa cells, it was 1.98 µL/mL (38.629 ng). Conclusion: The nanoparticles were three-fold toxic towards the HEK-293 cells in comparison to the HeLa cells. Therefore, the therapeutic index is low for R. apiculata derived AgNPs on HeLa cells when tested in comparison with the HEK-293 cells. The nanotoxicity profile of the synthesized AgNPs seems more prominent than the nanotherapeutic index. According to our knowledge, this is the first-ever report on the optimization of synthesis of AgNPs using response surface methodology and identifying the therapeutic index of mangrove leaf-derived AgNPs.


Asunto(s)
Nanopartículas del Metal/toxicidad , Plata/toxicidad , Pruebas de Toxicidad , Muerte Celular/efectos de los fármacos , Células HEK293 , Células HeLa , Humanos , Nanopartículas del Metal/ultraestructura , Análisis de Regresión , Difracción de Rayos X
19.
Carbohydr Polym ; 255: 117484, 2021 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-33436244

RESUMEN

Wound dressing composed of chitosan, based crosslinked gelatin/ polyvinyl pyrrolidone, embedded silver nanoparticles were fabricated using solution casting method. The membrane was characterized by FTIR, SEM and TGA. Glutaraldehyde (0.5 %) was used for the crosslinking of membrane components and associated with 7-folds boosted mechanical performance, 28 % more hydrolytic stability, 3-folds thickness reduction and morphological roughness. Silver nanoparticles were characterized by UV-vis, XRD and TEM for an average size of 9.9 nm. The membrane with higher concentration of silver nanoparticles showed maximum antibacterial activity against human pathogenic bacteria; and the measured inhibition zones ranged from 1.5 to 3 cm. The activity of the particles ranged from severe to complete reduction in Penicillin, Erythromycin and Macrolide family's resistance genes expression such as ß-Lactamase, mecA and erm. This developed membrane can serve as promising and cost-effective system against severe diabetic and burn wound infections.


Asunto(s)
Antibacterianos/farmacología , Vendajes , Quitosano/química , Citrullus colocynthis/química , Gelatina/química , Povidona/química , Plata/farmacología , Bacillus subtilis/efectos de los fármacos , Bacillus subtilis/crecimiento & desarrollo , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Farmacorresistencia Bacteriana Múltiple/efectos de los fármacos , Farmacorresistencia Bacteriana Múltiple/genética , Eritromicina/farmacología , Escherichia coli/efectos de los fármacos , Escherichia coli/crecimiento & desarrollo , Fibroblastos/citología , Fibroblastos/efectos de los fármacos , Regulación Bacteriana de la Expresión Génica/efectos de los fármacos , Humanos , Macrólidos/farmacología , Nanopartículas del Metal/química , Nanopartículas del Metal/ultraestructura , Metiltransferasas/genética , Metiltransferasas/metabolismo , Pruebas de Sensibilidad Microbiana , Proteínas de Unión a las Penicilinas/genética , Proteínas de Unión a las Penicilinas/metabolismo , Penicilinas/farmacología , Cultivo Primario de Células , Pseudomonas aeruginosa/efectos de los fármacos , Pseudomonas aeruginosa/crecimiento & desarrollo , Salmonella typhi/efectos de los fármacos , Salmonella typhi/crecimiento & desarrollo , Plata/química , Staphylococcus aureus/efectos de los fármacos , Staphylococcus aureus/crecimiento & desarrollo , beta-Lactamasas/genética , beta-Lactamasas/metabolismo
20.
Molecules ; 26(3)2021 Jan 22.
Artículo en Inglés | MEDLINE | ID: mdl-33499047

RESUMEN

Epidermal growth factor receptor (EGFR) is estimated to be overexpressed in 60~80% of colorectal cancer (CRC), which is associated with a poor prognosis. Anti-EGFR targeted monoclonal antibodies (cetuximab and panitumumab) have played an important role in the treatment of metastatic CRC. However, the therapeutic response of anti-EGFR monoclonal antibodies is limited due to multiple resistance mechanisms. With the discovery of new functions for gold nanoparticles (AuNPs), we hypothesize that cetuximab-conjugated AuNPs (cetuximab-AuNPs) will not only improve the cytotoxicity for cancer cells, but also introduce expression change of the related biomarkers on cancer cell surface. In this contribution, we investigated the size-dependent cytotoxicity of cetuximab-AuNPs to CRC cell line (HT-29), while also monitored the expression of cell surface biomarkers in response to treatment with cetuximab and cetuximab-AuNPs. AuNPs with the size of 60 nm showed the highest impact for cell cytotoxicity, which was tested by cell counting kit-8 (CCK-8) assay. Three cell surface biomarkers including epithelial cell adhesion molecule (EpCAM), melanoma cell adhesion molecule (MCAM), and human epidermal growth factor receptor-3 (HER-3) were found to be expressed at higher heterogeneity when cetuximab was conjugated to AuNPs. Both surface-enhanced Raman scattering/spectroscopy (SERS) and flow cytometry demonstrated the correlation of cell surface biomarkers in response to the drug treatment. We thus believe this study provides powerful potential for drug-conjugated AuNPs to enhance cancer prognosis and therapy.


Asunto(s)
Antineoplásicos Inmunológicos/administración & dosificación , Cetuximab/administración & dosificación , Neoplasias Colorrectales/tratamiento farmacológico , Nanopartículas del Metal/administración & dosificación , Biomarcadores de Tumor/metabolismo , Antígeno CD146/metabolismo , Supervivencia Celular/efectos de los fármacos , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/patología , Molécula de Adhesión Celular Epitelial/metabolismo , Oro , Células HT29 , Humanos , Nanopartículas del Metal/ultraestructura , Nanoconjugados/administración & dosificación , Nanoconjugados/ultraestructura , Tamaño de la Partícula , Fenotipo , Receptor ErbB-3/metabolismo , Transducción de Señal/efectos de los fármacos , Espectrometría Raman
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