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Melanoma has gained considerable attention due to its high mortality and morbidity rate worldwide. The currently available treatment options are associated with several limitations such as nonspecificity, drug resistance, easy clearance, low efficacy, toxicity-related issues, etc. To this end, nanotechnology has garnered significant attention for the treatment of melanoma. In the present manuscript, we have demonstrated the in vitro and in vivo anticancer activity of silver nitroprusside nanoparticles (abbreviated as AgNNPs) against melanoma. The AgNNPs exhibit cytotoxicity against B16F10 cells, which has been investigated by several in vitro experiments including [methyl 3H]-thymidine incorporation assay, cell cycle and apoptosis analysis by flow cytometry, and ROS generation through DCFDA, DHE, and DAF2A reagents. Further, the internalization of nanoparticles was determined by ICPOES analysis, while their colocalization was analyzed by confocal microscopy. Additionally, JC-1 staining is performed to examine mitochondrial membrane potential (MMP). Cytoskeleton integrity was observed by phalloidin staining. Expression of different markers (Ki-67, cytochrome c, and E-cadherin) was checked using an immunofluorescence assay. The in vivo therapeutic efficacy of AgNNPs has been validated in the melanoma model established by inoculating B16F10 cells into the dorsal right abdomen of C57BL/6J mice. The intraperitoneal administration of AgNNPs reduced melanoma growth and increased the survivability of tumor-bearing mice. The in vivo immunofluorescence studies (Ki-67, CD31, and E-cadherin) and TUNEL assay support the inhibitory and apoptotic nature of AgNNPs toward melanoma, respectively. Furthermore, the various signaling pathways and molecular mechanisms involved in anticancer activity are evaluated by Western blot analysis. These findings altogether demonstrate the promising anticancer potential of AgNNPs toward melanoma.
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Antineoplásicos , Apoptosis , Proliferación Celular , Ensayos de Selección de Medicamentos Antitumorales , Ratones Endogámicos C57BL , Nitroprusiato , Plata , Animales , Ratones , Antineoplásicos/farmacología , Antineoplásicos/química , Nitroprusiato/farmacología , Nitroprusiato/química , Apoptosis/efectos de los fármacos , Plata/química , Plata/farmacología , Proliferación Celular/efectos de los fármacos , Tamaño de la Partícula , Ensayo de Materiales , Melanoma/tratamiento farmacológico , Melanoma/patología , Nanopartículas del Metal/química , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Nanopartículas/química , Supervivencia Celular/efectos de los fármacos , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Línea Celular Tumoral , Especies Reactivas de Oxígeno/metabolismo , Melanoma Experimental/tratamiento farmacológico , Melanoma Experimental/patología , Melanoma Experimental/metabolismoRESUMEN
Bacterial infections can lead to the formation of chronic wounds and delay the wound-healing process. Therefore, it is important to explore safe and efficient antimicrobial agents that have wound-healing and biocompatible properties. In this study, novel starch-fabricated silver nitroprusside nanoparticles (S-AgNP NPs) were prepared for biocompatible wound-healing applications. The study showed that S-AgNP NPs are spherical, with an average size of 356 ± 22.28 d. nm and zeta potential of -27.8 ± 2.80 mV, respectively. Furthermore, the FTIR and XRD results showed that S-AgNP NPs have functional groups and crystal structures from the silver nitroprusside nanoparticles (AgNP NPs) and starch. Additionally, S-AgNP NPs showed excellent bacterial and biofilm inhibition on B. cereus (15.6 µg/mL), L. monocytogenes (15.6 µg/mL), S. aureus (31.3 µg/mL), E. coli (31.3 µg/mL) and S. enterica (62.5 µg/mL). Moreover, S-AgNP NPs promoted cell migration and proliferation at a concentration of 62.5 µg/mL compared to AgNP NPs. Meanwhile, S-AgNP NPs had good biocompatibility and low cytotoxicity compared to AgNP NPs. Therefore, this study provided new ideas for the development of wound-healing agents with bacteriostatic properties in chronic wounds.
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Banana (Musa acuminate) has been popular among consumers worldwide due to its rich nutrients and minerals. However, bananas are highly susceptible to the physical and biological factors that lead to postharvest loss during transportation and storage. In this work, novel sodium alginate (SA) films incorporated with silver nitroprusside nanoparticles (AgNNPs) were prepared to extend the shelf life of bananas through antibacterial and antioxidant coating. The results exhibited that AgNNPs were cubical and that their size was <500 nm, with metal composition being Ag and Fe. Additionally, the incorporation of AgNNPs in the SA film was seen in FE-SEM and zeta analysis, with an average size of about 365.6 nm. Furthermore, the functional and crystalline properties of AgNNPs were assessed through FTIR and XRD. Transmittance testing of the SA-AgNNPs films confirmed they have good UV barrier properties. SA-AgNNPs films exhibited excellent high antibacterial activity against foodborne pathogens including L. monocytogenes, S. enterica, and E. coli at the concentration of 500 µg/mL. Moreover, during the storage of bananas, SA-AgNNPs nanocomposite coatings act as a barrier to microbial contamination and slow down the ripening of bananas. As a result, compared with SA-coated and uncoated bananas, SA-AgNNPs-coated bananas exhibited the lowest weight loss and lowest total bacterial colonies, thus greatly extending their shelf life. Particularly when coated with SA-AgNNPs films, total bacterial colonies (TBC) in the banana peel and pulp were as low as 1.13 × 103 and 51 CUF/g on the ninth day of storage, respectively. Our work offers an efficient strategy to improve the quality of bananas during the postharvest period, with extensive applications in fruit preservation and food packing.
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INTRODUCTION: Chemodynamic therapy (CDT) holds great promise in achieving cancer therapy through Fenton and Fenton-like reactions, which generate highly toxic reactive species. However, CDT is limited by the lower amount of catalyst ions that can decompose already existing intracellular H2O2 and produce reactive oxygen species (ROS) to attain a therapeutic outcome. OBJECTIVES: To overcome these limitations, a tailored approach, which utilizes dual metals cations (Ag+, Fe2+) based silver pentacyanonitrosylferrate or silver nitroprusside (AgNP) were developed for Fenton like reactions that can specifically kill cancer cells by taking advantage of tumor acidic environment without used of any external stimuli. METHODS: A simple solution mixing procedure was used to synthesize AgNP as CDT agent. AgNP were structurally and morphologically characterized, and it was observed that a minimal dose of AgNP is required to destroy cancer cells with limited effects on normal cells. Moreover, comprehensive in vitro studies were conducted to evaluate antitumoral mechanism. RESULTS: AgNP have an effective ability to decompose endogenous H2O2 in cells. The decomposed endogenous H2O2 generates several different types of reactive species (â¢OH, O2â¢-) including peroxynitrite (ONOO-) species as apoptotic inducers that kill cancer cells, specifically. Cellular internalization data demonstrated that in short time, AgNP enters in lysosomes, avoid degradation and due to the acidic pH of lysosomes significantly generate high ROS levels. These data are further confirmed by the activation of different oxidative genes. Additionally, we demonstrated the biocompatibility of AgNP on mouse liver and ovarian organoids as an ex vivo model while AgNP showed the therapeutic efficacy on patient derived tumor organoids (PDTO). CONCLUSION: This work demonstrates the therapeutic application of silver nitroprusside as a multiple ROS generator utilizing Fenton like reaction. Thereby, our study exhibits a potential application of CDT against HGSOC (High Grade Serous Ovarian Cancer), a deadly cancer through altering the redox homeostasis.
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Neoplasias , Plata , Ratones , Animales , Humanos , Especies Reactivas de Oxígeno/metabolismo , Plata/química , Plata/farmacología , Plata/uso terapéutico , Nitroprusiato/farmacología , Nitroprusiato/uso terapéutico , Ácido Peroxinitroso/uso terapéutico , Peróxido de Hidrógeno/química , Neoplasias/tratamiento farmacológicoRESUMEN
There have been reports of different types of wound dressings for various functions and purposes. Cotton being one of the most widely used wound dressing material due to its non-toxic, biodegradable, and other properties is used for fabrication as well as in the form of scaffolds for faster and effective wound closure. Our research team has already demonstrated the role of silver nitroprusside nanoparticles (SNPNPs) for wound healing and antibacterial activity. In the current study, we have developed cotton fabric impregnated with SNPNPs (SNPCFs) which remain photo inert and displayed long-term antimicrobial activity due to the surface modification with the silver nitroprusside complex. These SNPCFs were characterized by various analytical techniques (XRD, FTIR, UV spectroscopy, TGA, TEM, FESEM, EDAX, ICP-OES). The fabricated cotton dressings with nanoparticles showed an improved water contact angle (113-130°) than that of bare cotton gauze (60°) and exhibited more antibacterial property in case of both Gram-negative bacteria (Klebsiella aerogenes and Escherichia coli) and Gram-positive bacteria (Pseudomonas aeruginosa and Bacillus subtilis) even after several washings. The biocompatible nature of SNPCFs was assessed by in vivo chorioallantoic membrane assay that showed no obstruction in the formation of blood vessels. The SNPCFs exhibited better wound healing activity compared to the bare cotton and AgCFs as observed in the C57BL6/J mouse. The histopathological investigation reveals increase in re-epithelialization and deposition of connective tissue. The macrophage (M2) counts in SNPCF-treated skin tissues were supportive of more wound healing activity than mice treated with cotton fabric impregnated with chemically synthesized silver nanoparticles. Based on biodistribution analysis using ICP-OES, the data illustrated that a significant amount of silver is absorbed in the skin tissues of mice as compared to the blood and kidney. Furthermore, the absence of silver from the vital organs (heart, liver, and kidney) corroborates our hypothesis that the SNPCFs can act excellently in treating wounds when topically applied over skin. Thereafter, all these results highlight a strong possibility that SNPCFs exemplify the potential as a new antimicrobial and wound healing agent in future times.
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Antibacterianos/uso terapéutico , Vendajes , Nanopartículas del Metal/uso terapéutico , Nitroprusiato/uso terapéutico , Compuestos de Plata/uso terapéutico , Cicatrización de Heridas/efectos de los fármacos , Animales , Antibacterianos/química , Antibacterianos/farmacocinética , Bacterias/efectos de los fármacos , Fibra de Algodón , Femenino , Gossypium/química , Nanopartículas del Metal/química , Ratones , Ratones Endogámicos C57BL , Pruebas de Sensibilidad Microbiana , Nitroprusiato/química , Nitroprusiato/farmacocinética , Células RAW 264.7 , Compuestos de Plata/química , Compuestos de Plata/farmacocinéticaRESUMEN
Therapeutic agents harboring both wound healing and antibacterial activities have much demand in biomedical applications. Development of such candidates with clinically approved materials adds more advantages toward these applications. Recently, silver metal complex nanomaterials have been playing a major role in medical uses especially for antibacterial activity and wound healing. In this report, we designed and synthesized silver nitroprusside complex nanoparticles (abbreviated as AgNNPs) using sodium nitroprusside and silver nitrate (both are FDA approved precursors). The nanoparticles (AgNNPs) were thoroughly characterized by various physicochemical techniques such as XRD, FTIR, TGA, DLS, EDAX, Raman, ICP-OES, HRTEM, and FESEM. The cell viability assay in normal cells (EA.hy 926 cells, NIH 3T3) using MTT reagents and CEA assay (CEA: Chick embryo angiogenesis assay) in fertilized eggs demonstrate the biocompatibility of AgNNPs. These nanoparticles show effective antibacterial activity against both Gram positive and Gram negative bacteria through membrane and DNA damage. Additionally, AgNNPs accelerate the wound healing in C57BL6 mice by altering the macrophages from M1 to M2. Considering the results together, the current study may offer the development of new silver nanocomplex nanomaterials that shows synergistic effect on antibacterial activity and wound healing (2-in-1-system). To the best of our knowledge, this is the first report for the synthesis, characterization, and biomedical applications of silver nitroprusside nanoparticles.
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Cystinuria is a common aminoaciduria due to a COAL transporter defect in renal tubular epithelium. Increased level of cystine in urine with occasional cystine crystal can be diagnostic. With reference to clinical examinations, symptoms and laboratory reports we present a case of primary cystinuria. Prevention of complication in cystinuric relies on detection at early stage and targeting treatment towards maintaining low level of urinary cystine level.