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1.
J Biochem Mol Toxicol ; 33(9): e22376, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31328346

RESUMO

Nickel oxide nanoparticles (NiO-NPs) are progressively used for an immense number of new applications in modern industries sectors. Nevertheless, the toxic impact of NiO-NPs has not been clearly elucidated on human melanoma cell lines at the cellular and molecular level. Hence, this study was designed to examine the in vitro cytotoxicity potentials of NiO-NPs on malignant cutaneous melanoma (MCM) mitochondria. Results revealed that NiO-NPs significantly increased reactive oxygen species level, lipid peroxidation, and mitochondrial membrane potential and decreased succinate dehydrogenase activity, glutathione level, and ATP content on skin mitochondria isolated from the mouse model of melanoma compared with the non-cancerous mouse skin mitochondria. Our results revealed that NiO-NPs induced lysosomal membrane labialization on mentioned mitochondria. The current study showed that NiO-NPs could significantly induce selective cytotoxicity on MCM mitochondria. Therefore, this compound may be considered as a promising candidate for further in vivo and clinical studies to reach a new anti-MCM drug.


Assuntos
Lisossomos/efeitos dos fármacos , Melanoma/patologia , Nanopartículas Metálicas/toxicidade , Mitocôndrias/efeitos dos fármacos , Níquel/química , Pele/efeitos dos fármacos , Animais , Modelos Animais de Doenças , Lisossomos/metabolismo , Masculino , Melanoma/metabolismo , Melanoma/ultraestrutura , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Mitocôndrias/metabolismo , Espécies Reativas de Oxigênio/metabolismo
2.
Adv Drug Deliv Rev ; 144: 162-179, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-31176755

RESUMO

Patient deaths resulting from cardiovascular diseases are increasing across the globe, posing the greatest risk to patients in developed countries. Myocardial infarction, as a result of inadequate blood flow to the myocardium, results in irreversible loss of cardiomyocytes which can lead to heart failure. A sequela of myocardial infarction is scar formation that can alter the normal myocardial architecture and result in arrhythmias. Over the past decade, a myriad of tissue engineering approaches has been developed to fabricate engineered scaffolds for repairing cardiac tissue. This paper highlights the recent application of electrically conductive nanomaterials (carbon and gold-based nanomaterials, and electroactive polymers) to the development of scaffolds for cardiac tissue engineering. Moreover, this work summarizes the effects of these nanomaterials on cardiac cell behavior such as proliferation and migration, as well as cardiomyogenic differentiation in stem cells.


Assuntos
Condutividade Elétrica , Infarto do Miocárdio/terapia , Nanoestruturas/administração & dosagem , Engenharia Tecidual , Animais , Materiais Biocompatíveis , Carbono/administração & dosagem , Ouro/administração & dosagem , Humanos , Miócitos Cardíacos/efeitos dos fármacos , Polímeros/administração & dosagem
3.
Artif Cells Nanomed Biotechnol ; 47(1): 2316-2324, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31184218

RESUMO

Nowadays, gold nanoshells are used in targeted nano photothermal cancer therapy. This study surveyed the application of gold nanoshell (GNs) to thermal ablative therapy for melanoma cancer cells and it takes advantage of the near infrared absorption of gold nanoshells. The synthesis and characterization of glycosylated gold nanoshells (GGNs) were done. The cytotoxicity and photothermal effects of GNs on melanoma cells were evaluated using MTT assay and flow cytometry. The characterization data showed that GGNs are spherical, with a hydrodynamic size of 46.7 nm. Results suggest that the cellular uptake of GGNs was about 78%. Viability assays showed no significant toxicity at low concentrations of GNs. The higher heating rate and toxicity of cancer cells were obtained for the cells exposed to 808 nm NIR laser after incubation with GGNs rather than the GNs. The viability of these cells has dramatically decreased by 29%. Furthermore, 61% more cell lethality was achieved for A375 cells using combined photothermal therapy and treatment with GGNs in comparison to NIR radiation alone. In conclusion, our findings suggest that the synthesized gold/silica core-shell nanoparticles conjugated with glucosamine have high potentials to be considered as an efficient metal-nanoshell in the process of targeted cancer photothermal therapy.


Assuntos
Ouro/química , Ouro/farmacologia , Raios Infravermelhos , Melanoma/patologia , Nanoconchas/química , Fototerapia/métodos , Temperatura , Linhagem Celular Tumoral , Glicosilação , Humanos , Melanoma/terapia , Nanopartículas/química , Dióxido de Silício/química
4.
Int J Biol Macromol ; 129: 1034-1039, 2019 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-30742919

RESUMO

Nowadays, regenerating peripheral nerves injuries (PNIs) remain a major clinical challenge, which has gained a great attention between scientists. Here, we represent a nanocomposite based on silk fibroin reinforced gold nanorods (SF/GNRs) to evaluate the proliferation and attachment of PC12 cells. The morphological characterization of nanocomposites with transmission electron microscopy (TEM) and Scanning electron microscopy (SEM) showed that the fabricated scaffolds have porous structure with interconnected pores that is suitable for cell adhesion and growth. GNRs significantly improved the poor electrical conductivity of bulk silk fibroin scaffold. Evaluating the morphology of PC12 cells on the scaffold also confirmed the normal morphology of cells with good rate of adhesion. SF/GNRs nanocomposites showed better cellular attachment, growth and proliferation without any toxicity compared with bulk SF scaffold. Moreover, immunostaining studies represented the overexpression of neural specific proteins like nestin and neuron specific enolase (NSE) in the cells cultured on SF/GNRs nanocomposites in comparison to neat SF scaffolds.


Assuntos
Materiais Biocompatíveis/farmacologia , Fibroínas/química , Ouro/química , Nanocompostos/química , Nanotubos/química , Nervos Periféricos/citologia , Engenharia Tecidual , Animais , Materiais Biocompatíveis/química , Adesão Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Condutividade Elétrica , Células PC12 , Ratos
5.
Toxicol Mech Methods ; 29(2): 86-94, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30132356

RESUMO

Today, nanoparticles (NPs) have been widely used in various fields. Manganese oxide nanoparticles have attracted a lot of attention due to many applications. One of the major concerns regarding the widespread use of various NPs is the exposure and accumulation in human organs and finally toxicity. The generation of reactive oxygen species (ROS) by mitochondria is one of the most important mechanisms of toxicity suggested by published studies induced by other NPs. However, limited studies have been conducted on the mechanism of toxicity of MnO2-NPs and MnO2-microparticles (MnO2-MPs). In this study, we compared the accumulation of MnO2-NPs and MnO2-MPs in different tissues and evaluated their effects on mitochondrial complexes in isolated mitochondria. Our results showed that intravascular (iv) administration of the MnO2-NPs in the same dose compared to the MnO2-MPs resulted in more accumulation in the C57 mouse female tissues. The effect of MnO2-NPs and MnO2-MPs in mitochondria showed that complexes I and III play an important role in increasing ROS generation and this effect is related to type of tissue. Also, our results showed that exposure to MnO2-NPs and MnO2-MPs reduced the activity of mitochondrial complexes II and IV. Our results suggest that the toxicity of the MnO2-NPs is higher than that of the MnO2-MPs and can lead to the depletion of antioxidant status, likely induction of apoptosis, cancer, and neurodegenerative disease. Abbreviations: NPs: nanoparticles; ROS: reactive oxygen species; SDH: succinate dehydrogenase; DCFH-DA: dichloro-dihydro-fluorescein diacetate; ELISA: enzyme-linked immunosorbent assay; MnO2-NPs: manganese oxide nanoparticles.


Assuntos
Complexo de Proteínas da Cadeia de Transporte de Elétrons/metabolismo , Nanopartículas Metálicas/toxicidade , Mitocôndrias/efeitos dos fármacos , Óxidos/toxicidade , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/enzimologia , Feminino , Rim/efeitos dos fármacos , Rim/enzimologia , Pulmão/efeitos dos fármacos , Pulmão/enzimologia , Compostos de Manganês/química , Nanopartículas Metálicas/química , Camundongos Endogâmicos C57BL , Mitocôndrias/enzimologia , Mitocôndrias Cardíacas/efeitos dos fármacos , Mitocôndrias Cardíacas/enzimologia , Mitocôndrias Hepáticas/efeitos dos fármacos , Mitocôndrias Hepáticas/enzimologia , Ovário/efeitos dos fármacos , Ovário/enzimologia , Estresse Oxidativo/efeitos dos fármacos , Óxidos/química , Tamanho da Partícula , Espécies Reativas de Oxigênio/metabolismo , Distribuição Tecidual
6.
Cell J ; 21(1): 14-26, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30507084

RESUMO

OBJECTIVE: The purpose of this study was to evaluate in vitro cytotoxicity of gold nanorods (GNRs) on the viability of spermatogonial cells (SSCs) and mouse acute lymphoblastic leukemia cells (EL4s). MATERIALS AND METHODS: In this experimental study, SSCs were isolated from the neonate mice, following enzymatic digestion and differential plating. GNRs were synthesized, then modified by silica and finally conjugated with folic acid to form F-Si-GNRs. Different doses of F-Si-GNRs (25, 50, 75, 100, 125 and 140 µM) were used on SSCs and EL4s. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) proliferation assay was performed to examine the GNRs toxicity. Flow cytometry was used to confirm the identity of the EL4s and SSCs. Also, the identity and functionality of SSCs were determined by the expression of specific spermatogonial genes and transplantation into recipient testes. Apoptosis was determined by flow cytometry using an annexin V/propidium iodide (PI) kit. RESULTS: Flow cytometry showed that SSCs and EL4s were positive for Plzf and H-2kb, respectively. The viability percentage of SSCs and EL4s that were treated with 25, 50, 75, 100, 125 and 140 µM of F-Si-GNRs was 65.33 ± 3.51%, 60 ± 3.6%, 51.33 ± 3.51%, 49 ± 3%, 30.66 ± 2.08% and 16.33 ± 2.51% for SSCs and 57.66 ± 0.57%, 54.66 ± 1.5%, 39.66 ± 1.52%, 12.33 ± 2.51%, 10 ± 1% and 5.66 ± 1.15% for EL4s respectively. The results of the MTT assay indicated that 100 µM is the optimal dose to reach the highest and lowest level of cell death in EL4s and in SSCs, respectively. CONCLUSION: Cell death increased with increasing concentrations of F-Si-GNRs. Following utilization of F-Si-GNRs, there was a significant difference in the extent of apoptosis between cancer cells and SSCs.

7.
Biomed Pharmacother ; 108: 1244-1252, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30453447

RESUMO

BACKGROUND: The aim of this study was to investigate the neurotoxic effects of Fe3O4 magnetic- CurNPs on isolated schizophrenia mitochondria of rats as an in vivo model. METHODS: We designed CMN loaded superparamagnetic iron oxide nanoparticles (SPIONs) (Fe3O4 magnetic- CurNPs) to achieve an enhanced therapeutic effect. The physicochemical properties of Fe3O4 magnetic- CurNPs were characterized using X-ray diffraction (XRD), and dynamic laser light scattering (DLS) and zeta potential. Further, to prove Fe3O4 magnetic- CurNPs results in superior therapeutic effects, and also, the mitochondrial membrane potential collapse, mitochondrial complex II activity, reactive oxygen species generation, ATP level, cytochrome c release and histopathology of cerebellums were determined in brains of schizophrenic rats. RESULTS: We showed that effective treatment with CMN reduced or prevented Fe3O4 magnetic-induced oxidative stress and mitochondrial dysfunction in the rat brain probably, as well as mitochondrial complex II activity, MMP, and ATP level were remarkably reduced in the cerebellum mitochondria of treated group toward control (p < 0.05). Therewith, ROS generation, and cytochrome c release were notably (p < 0.05) increased in the cerebellum mitochondria of treated group compared with control group. CONCLUSION: Taken together, Fe3O4 magnetic- CurNPs exhibits potent antineurotoxicity activity in cerebellums of schizophrenic rats. This approach can be extended to preclinical and clinical use and may have importance in schizophernia treatment in the future. To our knowledge this is the first report that provides the Fe3O4 magnetic- CurNPs could enhance the neuroprotective effects of CMN in the Schizophrenia.


Assuntos
Cerebelo/efeitos dos fármacos , Curcumina/administração & dosagem , Nanopartículas de Magnetita/administração & dosagem , Mitocôndrias/efeitos dos fármacos , Esquizofrenia/tratamento farmacológico , Trifosfato de Adenosina/metabolismo , Animais , Escala de Avaliação Comportamental , Cerebelo/metabolismo , Cerebelo/patologia , Curcumina/química , Citocromos c/metabolismo , Modelos Animais de Doenças , Nanopartículas de Magnetita/química , Masculino , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Neuroproteção , Fármacos Neuroprotetores/administração & dosagem , Fármacos Neuroprotetores/química , Distribuição Aleatória , Ratos , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismo , Esquizofrenia/metabolismo , Esquizofrenia/patologia
8.
Regul Toxicol Pharmacol ; 98: 240-244, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30102957

RESUMO

Metal nanoparticles (NPs) have been extensively used in industry as well as in biomedical application. Manganese oxide-nanoparticles (MnO2-NPs) one of these materials, have many applications. This study was designed to evaluate the protective role of vitamin D against MnO2-NPs -induced toxicity in the BALB c mice. These mice were randomly assigned to 4 (n = 10). In this study, MnO2-NPs (10 mg/kg), vitamin D (10 mg/kg) and MnO2-NPs plus vitamin D were administered interperitoneally once daily for 50 consecutive days. The liver and kidney functions, the levels of serum glucose, albumin (ALB), bilirubin (BIL) and total protein were studied. The results indicated that MnO2-NPs administration significantly decreased liver and kidney functions, and increased glucose and bilirubin serum levels compared to control group (P < 0.05). However, vitamin D administration significantly boosted liver and kidney functions, decreased glucose and bilirubin serum level compared to the group received MnO2-NPs (P < 0.05). It seems that vitamin D administration could protect the liver and kidney damage induced by MnO2-NPs. Probably, given the use of these nanoparticles as a contest agent in humans, having normal levels of vitamin D or receiving it at the time of the test can inhibit liver and kidney toxicity induced by MnO2-NPs.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Nefropatias/tratamento farmacológico , Nanopartículas Metálicas/toxicidade , Óxidos/toxicidade , Substâncias Protetoras/uso terapêutico , Vitamina D/uso terapêutico , Animais , Nefropatias/induzido quimicamente , Masculino , Compostos de Manganês , Camundongos Endogâmicos BALB C
9.
Int J Nanomedicine ; 13: 2943-2954, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29849458

RESUMO

BACKGROUND: Some male survivors of childhood cancer are suffering from azoospermia. In addition, spermatogonial stem cells (SSCs) are necessary for the improvement of spermatogenesis subsequent to exposure to cytotoxic agents such as cisplatin. OBJECTIVE: The aim of this study was to evaluate the anticancer activity of cisplatin-loaded folic acid-conjugated poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) on mouse malignant cell line (EL4) and SSCs in vitro. METHODS: SSCs were co-cultured with mouse malignant cell line (EL4) cells and divided into four culture groups: 1) control (cells were co-cultured in the culture medium), 2) co-cultured cells were treated with cisplatin (10 µg/mL), 3) co-cultured cells were treated with cisplatin-loaded folic acid-conjugated PLGA NPs, and 4) co-cultures were treated with folic acid-conjugated PLGA for 48 hours. The NPs were prepared, characterized, and targeted with folate. In vitro release characteristics, loading efficiency, and scanning electron microscopy and transmission electron microscopy images were studied. Cancer cells were assayed after treatment using flow cytometry and TUNEL assay. The co-cultures of SSCs and EL4 cells were injected into seminiferous tubules of the testes after treating with cis-diaminedichloroplatinum/PLGA NPs. RESULTS: The mean diameter of PLGA NPs ranged between 150 and 250 nm. The number of TUNEL-positive cells increased, and the expression of Bax and caspase-3 were upregulated in EL4 cells in Group 4 compared with Group 2. There was no pathological tumor in testes after transplantation with treated co-cultured cells. CONCLUSION: The PLGA NPs appeared to act as a promising carrier for cisplatin administration, which was consistent with a higher activation of apoptosis than free drug.


Assuntos
Antineoplásicos/administração & dosagem , Cisplatino/administração & dosagem , Ácido Fólico/química , Nanopartículas/administração & dosagem , Espermatogônias/patologia , Animais , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Técnicas de Cocultura , Portadores de Fármacos/administração & dosagem , Portadores de Fármacos/química , Ácido Fólico/administração & dosagem , Ácido Láctico/química , Masculino , Camundongos , Microscopia Eletrônica de Transmissão , Nanopartículas/química , Ácido Poliglicólico/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Túbulos Seminíferos/efeitos dos fármacos , Túbulos Seminíferos/patologia , Espermatogônias/efeitos dos fármacos
10.
J Biochem Mol Toxicol ; 32(6): e22056, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29719092

RESUMO

Silk fibroin nanoparticles (SFNPs) as a natural polymer have been utilized in biomedical applications such as suture, tissue engineering-based scaffolds, and drug delivery carriers. Since there is little data regarding the toxicity effects on different cells and tissues, we aimed to determine the toxicity mechanisms of SFNPs on human lymphocytes and monocytes based on reliable methods. Our results showed that SFNPs (0.5, 1, and 2 mg/mL) induced oxidative stress via increasing reactive oxygen species production, mitochondrial membrane potential (∆Ψ) collapse, which was correlated to cytochrome c release and Adenosine diphosphate (ADP)/Adenosine tri phosphate (ATP) ratio increase as well as lysosomal as another toxicity mechanism, which led to cytosolic release of lysosomal digestive proteases, phosphor lipases, and apoptosis signaling. Taken together, these data suggested that SFNPs toxicity was associated with mutual mitochondrial/lysosomal cross-talk and oxidative stress on human lymphocytes and monocytes with activated apoptosis signaling.


Assuntos
Fibroínas/toxicidade , Linfócitos/efeitos dos fármacos , Monócitos/efeitos dos fármacos , Estresse Oxidativo , Difosfato de Adenosina/metabolismo , Trifosfato de Adenosina/metabolismo , Apoptose , Células Cultivadas , Citocromos c/metabolismo , Complexo IV da Cadeia de Transporte de Elétrons/metabolismo , Glutationa/metabolismo , Humanos , Linfócitos/metabolismo , Lisossomos/efeitos dos fármacos , Lisossomos/metabolismo , Malondialdeído/metabolismo , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Monócitos/metabolismo , Nanopartículas , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais
11.
Int J Biol Macromol ; 118(Pt A): 1319-1325, 2018 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-29715556

RESUMO

Pirfenidone (PFD) is one of the pyridine family components with anti-inflammatory, antifibrotic effects and US FDA approved for the treatment of idiopathic pulmonary fibrosis (IPF). Presently, PFD is administered orally and this has setbacks. Hence, it is important to eliminate the pharmacotherapeutic limitations of PFD. This research was carried out to study the possibility of transdermal delivery of PFD using chitosan-sodium alginate nanogel carriers. In order to synthesize chitosan-sodium alginate nanoparticles loaded with PFD, the pre-gelation method was used. Scanning electron microscopy (SEM), transmission electron microscopy (TEM), dynamic light scattering (DLS), and Fourier-transform infrared spectroscopy (FTIR) analyses were used for the characterization. Drug encapsulation and release manner were studied using UV spectroscopy. Ex vivo permeation examinations were performed using Franz diffusion cell and fluorescence microscopy. The results showed that nanoparticles having spherical morphology and size in the range of 80 nm were obtained. In vitro drug release profile represents sustained release during 24 h, while 50% and 94% are the loading capacity and efficiency, respectively. Also, the skin penetration of PFD loaded in nanoparticles was significantly increased as compared to PFD solution. The obtained results showed that synthesized nanoparticles can be considered as promising carriers for PFD delivery.


Assuntos
Alginatos , Quitosana , Portadores de Fármacos , Fibrose Pulmonar Idiopática/tratamento farmacológico , Piridonas , Administração Cutânea , Alginatos/química , Alginatos/farmacocinética , Alginatos/farmacologia , Animais , Quitosana/química , Quitosana/farmacocinética , Quitosana/farmacologia , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Portadores de Fármacos/farmacologia , Ácido Glucurônico/química , Ácido Glucurônico/farmacocinética , Ácido Glucurônico/farmacologia , Ácidos Hexurônicos/química , Ácidos Hexurônicos/farmacocinética , Ácidos Hexurônicos/farmacologia , Humanos , Fibrose Pulmonar Idiopática/metabolismo , Fibrose Pulmonar Idiopática/patologia , Camundongos , Piridonas/química , Piridonas/farmacocinética , Piridonas/farmacologia , Pele/metabolismo , Pele/patologia
12.
Iran J Pharm Res ; 17(Suppl2): 134-145, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-31011348

RESUMO

Emerging line research showed that silk nanoparticles (NPs) have toxicity on the fibroblast and Huvec cells without any toxicity recognized mechanisms. Recently, it suggested peripheral arterial disease confounds almost eight million Americans. Also, due to the main effect of fibroblast in a production of extracellular matrix (ECM), adhesive molecules, glycoproteins and various cytokines, it decided to define the toxicity mechanistic of silk NPs in fibroblast and Huvec cells based on oxidative stress markers. Therefore, it investigated whether silk NPs is able to induce any abnormality in the fibroblast and Huvec cells based on reliable and documented oxidative stress methods. Our results indicated that silk NPs (0.5, 1 and 2 mg/mL) induces cellular and mitochondrial dysfunction including an increase in ROS production, lipid peroxidation, mitochondria membrane potential (MMP) collapse, and oxidation of thiol groups which caused to cytochrome c release. Besides, lysosomal integrity damage and decreased in ATP/ADP ratio proposed disruptive effect of silk NPs on the mitochondrial respiratory chain and cell death signaling induction.

13.
J Biomed Mater Res A ; 106(2): 580-589, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-28884517

RESUMO

As the applications of titanium dioxide nanomaterials (nTiO2 ) are growing with an ever-increasing speed, the hazardous risks of this material have become a major concern. Several recent studies have reported that nTiO2 can cross the placental barrier in pregnant mice and cause neurotoxicity in their offspring. However, the influence of these nanoparticles on the fetoplacental unit during the pregnancy is yet to be studied. The present study reports on the effects of nTiO2 on the anatomical structure of fetal brain and liver in a pregnant mice model. Moreover, changes in the size and weight of the fetus and placenta are investigated as markers of fetal growth. Lastly, the toxicity of nTiO2 in primary brain and liver is quantified. Animals treated with nTiO2 showed a disrupted anatomical structure of the fetal brain and liver. Furthermore, the fetus and placental unit in the mice treated with these nanoparticles were smaller compared to untreated controls. Toxicity analyses revealed that nTiO2 was toxic to the brain and liver cells and the mechanism of cell death was mostly necrosis. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 580-589, 2018.


Assuntos
Materiais Biocompatíveis/farmacologia , Feto/efeitos dos fármacos , Teste de Materiais , Nanopartículas/química , Placenta/efeitos dos fármacos , Titânio/farmacologia , Animais , Apoptose/efeitos dos fármacos , Encéfalo/citologia , Córtex Cerebral/efeitos dos fármacos , Feminino , Feto/anatomia & histologia , Ventrículos do Coração/efeitos dos fármacos , Fígado/anatomia & histologia , Fígado/citologia , Camundongos , Nanopartículas/ultraestrutura , Necrose , Tamanho do Órgão/efeitos dos fármacos , Placenta/anatomia & histologia , Gravidez , Difração de Raios X
14.
Int J Biol Macromol ; 109: 955-962, 2018 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-29154878

RESUMO

Despite frequent scientific efforts, efficient ocular drug delivery is a major challenge for pharmaceutical scientists. Poor bioavailability of ophthalmic solutions can be overcome by using smart ophthalmic drug-delivery systems. In this research, loading and delivery of Timolol Maleate (TM) through the cornea by synthesized nanoparticles based on biopolymers (chitosan-alginate) were studied. The physico-chemical properties of these nanoparticles were characterized using scanning electron microscopy (SEM), transmission electron microscopy (TEM) and dynamic light scattering (DLS). Loading and release were evaluated by a UV-vis spectrometer and the ex vivo permeation study was carried out using the Franz Diffusion Cell and fluorescent microscopy studies. The results indicated that morphology and size of nanoparticles were spherical and in the range of 80-100nm. The loading capacity and encapsulation efficiency were about 42% and 94% respectively. They illustrated a burst release in the first hour followed by a slower and more sustained drug release during the next 24h. Also, the results indicated that the cornea penetration of TM loaded in nanoparticles was twice than that of TM. Hence, this nanocarrier can be considered as a suitable candidate for controlled TM delivery and release through the cornea.


Assuntos
Produtos Biológicos/química , Córnea/efeitos dos fármacos , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos , Géis/química , Nanocompostos/química , Polímeros/química , Timolol/administração & dosagem , Liberação Controlada de Fármacos , Estabilidade de Medicamentos , Glaucoma , Nanocompostos/ultraestrutura , Nanopartículas/química , Nanopartículas/ultraestrutura , Tamanho da Partícula , Permeabilidade , Espectroscopia de Infravermelho com Transformada de Fourier , Timolol/farmacocinética , Viscosidade
15.
Cutan Ocul Toxicol ; 37(2): 157-166, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28768445

RESUMO

PURPOSE: Nanomaterials (NM) exhibit novel anticancer properties. MATERIALS AND METHODS: The toxicity of three nanoparticles that are currently being produced in high tonnage including single-walled carbon nanotube (SWCNT), multi-walled carbon nanotube (MWCNT) and Fe2O3 nanoparticles, were compared with normal and melanoma cells. RESULTS: All tested nanoparticles induced selective toxicity and caspase 3 activation through mitochondria pathway in melanoma cells and mitochondria cause the generating of reactive oxygen species (ROS), mitochondrial membrane potential decline (MMP collapse), mitochondria swelling, and cytochrome c release. The pretreatment of butylated hydroxytoluene (BHT), a cell-permeable antioxidant and cyclosporine A (Cs. A), a mitochondrial permeability transition (MPT), pore sealing agent decreased cytotoxicity, caspase 3 activation, ROS generation, and mitochondrial damages induced by SWCNT, MWCNT, and IONPs. CONCLUSIONS: Our promising results provide a potential approach for the future therapeutic use of SWCNT, MWCNT, and IONPs in melanoma through mitochondrial targeting.


Assuntos
Antineoplásicos/farmacologia , Compostos Férricos/farmacologia , Mitocôndrias/efeitos dos fármacos , Nanopartículas , Nanotubos de Carbono , Animais , Apoptose/efeitos dos fármacos , Caspase 3/metabolismo , Citocromos c/metabolismo , Melanoma/metabolismo , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Camundongos , Mitocôndrias/metabolismo , Mitocôndrias/fisiologia , Espécies Reativas de Oxigênio/metabolismo , Succinato Desidrogenase/metabolismo , Células Tumorais Cultivadas
16.
Biomed Environ Sci ; 30(8): 581-590, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28807098

RESUMO

OBJECTIVE: Scorpion (Hemiscorpius lepturus) stings are a public health concern in Iran, particularly in south and southwestern regions of Iran. The gold standard for the treatment of a scorpion sting is anti-venom therapy. However, immunotherapy can have serious side effects, such as anaphylactic shock (which can sometimes even lead to death). The aim of the current study was to demonstrate the protective effect of ozone against toxicity induced by Hemiscorpius lepturus (H. lepturus) venom in mice. METHODS: Eight hours after the injection of ozone to the experimental design groups, the male mice were decapitated and mitochondria were isolated from five different tissues (liver, kidney, heart, brain, and spinal cord) using differential ultracentrifugation. Then, assessment of mitochondrial parameters including mitochondrial reactive oxidative species (ROS) production, mitochondrial membrane potential (MMP), ATP level, and the release of cytochrome c from the mitochondria was performed. RESULTS: Our results showed that H. lepturus venom-induced oxidative stress is related to ROS production and MMP collapse, which is correlated with cytochrome c release and ATP depletion, indicating the predisposition to the cell death signaling. CONCLUSION: In general, ozone therapy in moderate dose can be considered as clinically effective for the treatment of H. lepturus sting as a protective and antioxidant agent.


Assuntos
Ozônio/farmacologia , Venenos de Escorpião/toxicidade , Escorpiões/fisiologia , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Citocromos c/metabolismo , Coração/efeitos dos fármacos , Rim/efeitos dos fármacos , Rim/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos BALB C , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/metabolismo , Miocárdio/metabolismo , Medula Espinal/efeitos dos fármacos , Medula Espinal/metabolismo
17.
J Biomed Mater Res A ; 105(7): 2047-2055, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28296041

RESUMO

With the ever-increasing use of carbon nanotubes (CNTs) in health-related and engineering applications, the hazardous risks of this material have become a major concern. It is well known that CNTs accumulate with cytotoxic and genotoxic levels within vital organs. It has also been shown that treating cell cultures with CNTs resulted in cell-cycle arrest and increased apoptosis/necrosis. The goal of this pilot study is to perform a comprehensive comparative study on the toxicity of single-wall (SW) and multiwall (MW) CNTs in rat skin cells. Our results confirm a dose-dependent toxicity of SWCNTs and MWCNTs due to the loss of mitochondrial activity, increase in mitochondrial reactive oxygen species (ROS) formation, and mitochondrial membrane potential collapse before mitochondrial swelling. Moreover, disturbance in the oxidative phosphorylation is observed by a decrease in ATP level. These events induced the release of cytochrome c via outer membrane rupture or MPT pore opening and subsequently programmed cell death of all doses compared to control group. Our results demonstrate that although MWCNTs can be very toxic, SWCNTs cause more mitochondrial damage to the cells. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 2047-2055, 2017.


Assuntos
Apoptose , Pontos de Checagem do Ciclo Celular , Mitocôndrias/metabolismo , Nanotubos de Carbono/química , Estresse Oxidativo , Animais , Masculino , Camundongos , Ratos
18.
Mol Imaging Biol ; 19(4): 522-530, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-27957646

RESUMO

PURPOSE: Early stage diseases diagnosed using magnetic resonance imaging (MRI) techniques is of high global interest as a potent noninvasive modality. MRI contrast agents are improved through modifications in structural and physicochemical properties of the applied nanoprobes. But, the potential toxic effects of nanoprobes upon exposure to biological systems are still a major concern. PROCEDURE: In this study, the acute toxicity of glycosylated Gd3+-based silica mesoporous nanospheres (GSNs) as a MRI contrast agent was evaluated in Balb/c mice. In order to evaluate in vivo toxicity of GSN, preclinical studies, daily weight monitoring, hematological/blood chemistry tests, and histological assessment were conducted. Magnetic resonance relaxivities of GSN was determined using a MRI scanner. RESULTS: The obtained results suggest that in vivo toxicity of GSN was mostly influenced by nanoparticle surface area, functionality, and nanoparticle zeta potential. The maximum tolerated dose (MTD) increased in the following order: mesoporous silica nanospheres (MSNs) at 1 mg/mice < GSN (aspect ratio 1, 2, 8) at 40 mg/mice. The results also indicate GSN, one of the best cell imaging contrast agent, which does not show any significant toxicity on multiple vital organs following injection of 20 mg/mice, while a significant T1-weighted enhancement was observed in whole body of a Balb/c mice 15 min postinjection of (5 µmol/kg) of body weight of GSN. CONCLUSIONS: These results shed light on the functionality of MSNs to minimize in vivo toxicity. Also, glyconanoprobe can be beneficially used for nanomedicine and cellular imaging applications without any significant toxicity.


Assuntos
Gadolínio/toxicidade , Nanosferas/toxicidade , Dióxido de Silício/toxicidade , Testes de Toxicidade Aguda , Animais , Glicosilação , Rim/efeitos dos fármacos , Rim/patologia , Imageamento por Ressonância Magnética , Masculino , Dose Máxima Tolerável , Camundongos Endogâmicos BALB C , Porosidade
19.
Biosens Bioelectron ; 77: 99-106, 2016 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-26397420

RESUMO

Circulating miRNAs are emerging as novel reliable biomarkers for early detection of cancer diseases. Through combining the advantages of electrochemical methods and nanomaterials with the selectivity of the oligo-hybridization-based biosensors, a novel electrochemical nanobiosensor for plasma miR-155 detection have demonstrated here, based on thiolated probe-functionalized gold nanorods (GNRs) decorated on the graphene oxide (GO) sheet on the surface of the glassy carbon electrode (GCE). The reduction signals of a novel intercalating label Oracet Blue (OB), were measured by differential pulse voltammetry (DPV) method. The transmission electron microscope (TEM) imaging, UV-vis spectrophotometry, cyclic voltammetry (CV), field emission scanning electron microscope (FE-SEM) imaging and energy dispersive spectroscopy (EDS) were proved the right synthesis of the GNRs and correct assembly of the modified electrode. The electrochemical signal had a linear relationship with the concentration of the target miRNA ranging from 2.0 fM to 8.0 pM, and the detection limit was 0.6 fM. Furthermore, the nanobiosensor showed high Specificity, and was able to discriminate sharply between complementary target miRNA, single-, three-base mismatch, and non-complementary miRNA. Alongside the outstanding sensitivity and selectivity, this nanobiosensor had great storage ability, reproducibility, and showed a decent response in the real sample analysis with plasma. In conclusion, the proposed electrochemical nanobiosensor could clinically be used in the early detection of the breast cancer, by direct detection of the plasma miR-155 in real clinical samples, without a need for sample preparation, RNA extraction and/or amplification.


Assuntos
Técnicas Biossensoriais/instrumentação , Neoplasias da Mama/diagnóstico , Condutometria/instrumentação , Detecção Precoce de Câncer/instrumentação , MicroRNAs/sangue , Nanotubos/química , Biomarcadores Tumorais/sangue , Neoplasias da Mama/sangue , Desenho de Equipamento , Análise de Falha de Equipamento , Ouro/química , Grafite/química , Nanopartículas Metálicas/química , Nanopartículas Metálicas/ultraestrutura , Nanotecnologia/instrumentação , Nanotubos/ultraestrutura , Óxidos/química , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
20.
Int J Biol Macromol ; 50(4): 1063-9, 2012 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-22269345

RESUMO

Silica-encapsulated magnetic nanoparticles (MNPs) were prepared via microemulsion method. The products were characterized by high resolution transmission electron microscopy (HRTEM) and energy-dispersive X-ray spectrum (EDS). MNPs with no observed cytotoxic activity against human lung carcinoma cell and brine shrimp lethality were used as suitable support for glucose oxidase (GOD) immobilization. Binding of GOD onto the support was confirmed by the FTIR spectra. The amount of immobilized GODs was 95 mg/g. Storage stability study showed that the immobilized GOD retained 98% of its initial activity after 45 days and 90% of the activity was also remained after 12 repeated uses. Considerable enhancements in thermal stabilities were observed for the immobilized GOD at elevated temperatures up to 80°C and the activity of immobilized enzyme was less sensitive to pH changes in solution.


Assuntos
Enzimas Imobilizadas/química , Glucose Oxidase/química , Imãs/química , Nanopartículas/química , Nanopartículas/toxicidade , Dióxido de Silício/química , Animais , Cápsulas , Bovinos , Linhagem Celular Tumoral , Estabilidade Enzimática , Enzimas Imobilizadas/metabolismo , Glucose Oxidase/metabolismo , Humanos , Concentração de Íons de Hidrogênio , Cinética , Propriedades de Superfície , Temperatura
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