RESUMEN
The purpose of this study was to investigate the effect of gold nanoparticles on the signaling cascade related to angiogenesis and vascular permeability induced by Vascular Endothelial Growth Factor (VEGF) in Bovine retinal endothelial cells (BRECs). The effect of VEGF and gold nanoparticles on cell viability, migration and tubule formation was assessed. PP2 (Src Tyrosine Kinase inhibitor) was used as the positive control and the inhibitor assay was performed to compare the effect of AuNPs on VEGF induced angiogenesis. The transient transfection assay was performed to study the VEGFR2/Src activity during experimental conditions and was confirmed using western blot analysis. Treatment of BRECs with VEGF significantly increased the cell proliferation, migration and tube formation. Furthermore, gold nanoparticles (500 nM) significantly inhibited the proliferation, migration and tube formation, in the presence of VEGF in BRECs. The gold nanoparticles also inhibited VEGF induced Src phosphorylation through which their mode of action in inhibiting angiogenic pathways is revealed. The fate of the gold nanoparticles within the cells is being analyzed using the TEM images obtained. The potential of AuNPs to inhibit the VEGF165-induced VEGFR-2 phosphorylation is also being confirmed through the receptor assay which elucidates one of the possible mechanism by which AuNPs inhibit VEGF induced angiogenesis. These results indicate that gold nanoparticles can block VEGF activation of important signaling pathways, specifically Src in BRECs and hence modulation of these pathways may contribute to gold nanoparticles ability to block VEGF-induced retinal neovascularization.
Asunto(s)
Permeabilidad Capilar/efectos de los fármacos , Células Endoteliales/enzimología , Oro/química , Nanopartículas del Metal/química , Neovascularización Fisiológica/efectos de los fármacos , Factor A de Crecimiento Endotelial Vascular/farmacología , Familia-src Quinasas/metabolismo , Animales , Bioensayo , Bovinos , Permeabilidad de la Membrana Celular/efectos de los fármacos , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Dextranos/metabolismo , Células Endoteliales/citología , Células Endoteliales/efectos de los fármacos , Células Endoteliales/ultraestructura , Humanos , Nanopartículas del Metal/ultraestructura , Fosforilación/efectos de los fármacos , Retina/citología , Rodaminas/metabolismo , Transducción de Señal/efectos de los fármacos , Transfección , Receptor 2 de Factores de Crecimiento Endotelial Vascular/metabolismoRESUMEN
BACKGROUND: Oxidative stress is imperative for its morbidity towards diabetic complications, where abnormal metabolic milieu as a result of hyperglycemia, leads to the onset of several complications. A biological antioxidant capable of inhibiting oxidative stress mediated diabetic progressions; during hyperglycemia is still the need of the era. The current study was performed to study the effect of biologically synthesized gold nanoparticles (AuNPs) to control the hyperglycemic conditions in streptozotocin induced diabetic mice. RESULTS: The profound control of AuNPs over the anti oxidant enzymes such as GSH, SOD, Catalase and GPx in diabetic mice to normal, by inhibition of lipid peroxidation and ROS generation during hyperglycemia evidence their anti-oxidant effect during hyperglycemia. The AuNPs exhibited an insistent control over the blood glucose level, lipids and serum biochemical profiles in diabetic mice near to the control mice provokes their effective role in controlling and increasing the organ functions for better utilization of blood glucose. Histopathological and hematological studies revealed the non-toxic and protective effect of the gold nanoparticles over the vital organs when administered at dosage of 2.5 mg/kilogram.body.weight/day. ICP-MS analysis revealed the biodistribution of gold nanoparticles in the vital organs showing accumulation of AuNPs in the spleen comparatively greater than other organs. CONCLUSION: The results obtained disclose the effectual role of AuNPs as an anti-oxidative agent, by inhibiting the formation of ROS, scavenging free radicals; thus increasing the anti-oxidant defense enzymes and creating a sustained control over hyperglycemic conditions which consequently evoke the potential of AuNPs as an economic therapeutic remedy in diabetic treatments and its complications.
RESUMEN
Biofilms are ensued due to bacteria that attach to surfaces and aggregate in a hydrated polymeric matrix. Formation of these sessile communities and their inherent resistance to anti-microbial agents are the source of many relentless and chronic bacterial infections. Such biofilms are responsible play a major role in development of ocular related infectious diseases in human namely microbial keratitis. Different approaches have been used for preventing biofilm related infections in health care settings. Many of these methods have their own demerits that include chemical based complications; emergent antibiotic resistant strains, etc. silver nanoparticles are renowned for their influential anti-microbial activity. Hence the present study over the biologically synthesized silver nanoparticles, exhibited a potential anti-biofilm activity that was tested in vitro on biofilms formed by Pseudomonas aeruginosa and Staphylococcus epidermidis during 24-h treatment. Treating these organisms with silver nanoparticles resulted in more than 95% inhibition in biofilm formation. The inhibition was known to be invariable of the species tested. As a result this study demonstrates the futuristic application of silver nanoparticles in treating microbial keratitis based on its potential anti-biofilm activity.
Asunto(s)
Biopelículas/efectos de los fármacos , Biopelículas/crecimiento & desarrollo , Nanopartículas del Metal/química , Pseudomonas aeruginosa/fisiología , Plata/farmacología , Staphylococcus epidermidis/fisiología , Antibacterianos/farmacología , Adhesión Bacteriana/efectos de los fármacos , Nanopartículas del Metal/ultraestructura , Pruebas de Sensibilidad Microbiana , Pseudomonas aeruginosa/efectos de los fármacos , Staphylococcus epidermidis/efectos de los fármacosRESUMEN
Pathological retinal angiogenesis (neovascularization) is one of the most feared complications among retinal diseases, leading to visual impairment and irreversible blindness. Recent findings made by us on therapeutic applications of biologically synthesized silver nanoparticles (AgNPs) against VEGF induced retinal endothelial cells, elucidates the effectual inhibitory activities of AgNPs over the downstream signaling pathways (Src and AKT/PI3K) leading to retinal angiogenesis. The current review focuses on the imperative role of VEGF induced angiogenesis in the development of retinal neovascularization and despite the fact that several VEGF targeting ocular drugs are available; the review examines the need for a cost economic alternative, thereby suggesting the role of AgNPs as an emerging economic ocular drug for retinal therapies. The current technologies available for the development of targeted and controlled release of drugs is being discussed and a model has been proposed for the amenable targeting mechanism, by which Poly gamma glutamic acid (PGA) capsulated AgNPs conjugated to cyclic RGD peptides carry out a sustained controlled release specifically targeting the neovascularization cells and induce apoptosis unaffecting the normal retinal cells. These constructs consequently affirm the futuristic application of silver nanoparticles as a boon to ocular therapies.
Asunto(s)
Preparaciones de Acción Retardada/farmacología , Nanopartículas del Metal/uso terapéutico , Retina/metabolismo , Enfermedades de la Retina/tratamiento farmacológico , Plata/farmacología , Factor A de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Animales , Bovinos , Células Cultivadas , Preparaciones de Acción Retardada/metabolismo , Perros , Relación Dosis-Respuesta a Droga , Células Endoteliales/metabolismo , Ojo/metabolismo , Humanos , Nanopartículas del Metal/química , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Nanomedicina/tendencias , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ratas , Retina/citología , Enfermedades de la Retina/patología , Neovascularización Retiniana/metabolismo , Transducción de Señal/efectos de los fármacos , Plata/metabolismo , Porcinos , Factor A de Crecimiento Endotelial Vascular/metabolismo , Factor A de Crecimiento Endotelial Vascular/uso terapéutico , Factores de Crecimiento Endotelial Vascular/metabolismoRESUMEN
The present study demonstrates an unprecedented green process for the production of spherical-shaped Au and Ag nanoparticles synthesized and stabilized using a bacterium, Brevibacterium casei. Aqueous solutions of chloroaurate ions for Au and Ag(+) ions for silver were treated with B. casei biomass for the formation of Au nanoparticles (AuNP) and Ag nanoparticles (AgNP). The nanometallic dispersions were characterized by surface plasmon absorbance measuring at 420 and 540 nm for Ag and Au nanoparticles, respectively. Transmission electron microscopy showed the formation of nanoparticles in the range of 10-50 nm (silver), and 10-50 nm (gold). XRD analysis of the silver and gold nanoparticles confirmed the formation of metallic silver and gold. Further analysis carried out by Fourier Transform Infrared Spectroscopy (FTIR), provides evidence for the presence of proteins as possible biomolecules responsible for the reduction and capping agent which helps in increasing the stability of the synthesized silver and gold nanoparticles. The biological activities of the synthesized particles were confirmed based on their stable anti-coagulant effects. The use of bacterium for nanoparticles synthesis offers the benefits of ecofriendliness and amenability for large-scale production.