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1.
Cent Eur J Public Health ; 28(3): 202-207, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32997476

RESUMO

OBJECTIVE: Nanomaterials consist of particles smaller than 100 nm - nanoparticles (NPs). Their nano dimensions allow them to penetrate through various membranes and enter into the bloodstream and disseminate into different body organs. Massive expansion of nanotechnologies together with production of new nanoparticles which have not yet been in contact with living organisms may pose a potential health problem. It is therefore necessary to investigate the health impact of NPs after experimental exposure. Comparison of the effect of TiO2 and NPs Fe3O4 in Wistar rats at time intervals 1, 7, 14 and 28 days was performed by studying the cytotoxic effect in the isolated inflammatory cells from bronchoalveolar lavage (BAL). METHODS: Wistar rats were intravenously (i.v.) given a suspension of NPs TiO2 or Fe3O4 (coated by sodium oleate) via the tail vein. After time intervals of 1, 7, 14 and 28 days, we sacrificed the animals under anaesthesia, performed BAL and isolated the cells. The number of animals in the individual groups was 7-8. We examined the differential count of BAL cells (alveolar macrophages - AM, polymorphonuclear leukocytes - PMN, lymphocytes - Ly); viability and phagocytic activity of AM; the proportion of immature and polynuclear cells and enzymes - cathepsin D - CAT D, lactate dehydrogenase - LDH and acid phosphatase - ACP. RESULTS: We found that TiO2 NPs are relatively inert - without induction of inflammatory and cytotoxic response. Exposure to nanoparticles Fe3O4 induced - under the same experimental conditions - in comparison with the control and TiO2 a more extensive inflammatory and cytotoxic response, albeit only at 1, 7 and 14 days after injection. CONCLUSIONS: The results suggest that TiO2 and Fe3O4 nanoparticles used in our study were transferred from the bloodstream to the respiratory tract, but this effect was not observed at 28 days after i.v. injection, probably due to their removal from the respiratory tract.


Assuntos
Óxido Ferroso-Férrico/toxicidade , Nanopartículas Metálicas/toxicidade , Doenças Respiratórias/induzido quimicamente , Titânio/toxicidade , Administração Intravenosa , Animais , Óxido Ferroso-Férrico/administração & dosagem , Nanopartículas Metálicas/administração & dosagem , Ratos , Ratos Wistar , Titânio/administração & dosagem
2.
J Toxicol Sci ; 45(8): 411-422, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32741894

RESUMO

Lanthanum oxide (La2O3) nanoparticles (NPs) have been widely used in photoelectric and catalytic applications. However, their exposure and reproductive toxicity is unknown. In this study, the effect of the intragastric administration of two different-sized La2O3 particles in the testes of mice for 60 days was investigated. Although the body weight of mice treated or not treated with La2O3 NPs was not different and La2O3 NPs were distributed in the organs including the testis, liver, kidney, spleen, heart and brain. La2O3 NPs accumulate more than micro-sized La2O3 (MPs) in mice testes. The histopathological evaluation showed that moderate reproductive toxicity induced by La2O3 NPs in the testicle tissues. Furthermore, increased MDA, 8-OHdG levels and decreased SOD activities were detected in the La2O3 NP-treated groups. Moreover, qRT-PCR and western blotting data indicated that La2O3 NPs affecting the blood-testis barrier (BTB)-related genes in mice testes. Taken together, these findings suggested that La2O3 NPs activated inflammation responses and cross the BTB in the murine testes. This study provided useful information for risk analysis and regulation of La2O3 NPs by administrative agencies.


Assuntos
Lantânio/administração & dosagem , Lantânio/toxicidade , Nanopartículas Metálicas/toxicidade , Óxidos/administração & dosagem , Óxidos/toxicidade , Tamanho da Partícula , Reprodução/efeitos dos fármacos , Testículo/efeitos dos fármacos , Administração Oral , Animais , Barreira Hematotesticular/metabolismo , Desoxiadenosinas/metabolismo , Expressão Gênica/efeitos dos fármacos , Inflamação , Lantânio/metabolismo , Masculino , Malondialdeído/metabolismo , Nanopartículas Metálicas/administração & dosagem , Camundongos , Óxidos/metabolismo , Superóxido Dismutase/metabolismo , Testículo/metabolismo , Distribuição Tecidual
3.
Int J Nanomedicine ; 15: 4705-4716, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32636626

RESUMO

Purpose: Ultra-small gold nanoclusters (AuNCs), as emerging fluorescent nanomaterials with excellent biocompatibility, have been widely investigated for in vivo biomedical applications. However, their effects in guiding osteogenic differentiation have not been investigated, which are important for osteoporosis therapy and bone regeneration. Herein, for the first time, lysozyme-protected AuNCs (Lys-AuNCs) are used to stimulate osteogenic differentiation, which have the potential for the treatment of bone disease. Methods: Proliferation of MC3T3E-1 is important for osteogenic differentiation. First, the proliferation rate of MC3T3E-1 was studied by Cell Counting Kit-8 (CCK8) assays. Signaling pathways of PI3K/Akt play central roles in controlling proliferation throughout the body. The expression of PI3K/Akt was investigated in the presence of lysozyme, and lysozyme-protected AuNCs (Lys-AuNCs) by Western blot (WB) and intracellular cell imaging to evacuate the osteogenic differentiation mechanisms. Moreover, the formation of osteoclasts (OC) plays a negative role in the differentiation of osteoblasts. Nuclear factor κB ligand (RANKL) and macrophage colony-stimulating factor (M-CSF) signaling pathways are used to understand the negative influence of the osteogenic differentiation by the investigation of Raw 264.7 cell line. Raw 264.7 (murine macrophage-like) cells and NIH/3T3 (mouse fibroblast) cells were treated with tyloxapol, and the cell viability was assessed. Raw 264.7 cells have also been used for in vitro studies, on understanding the osteoclast formation and function. The induced osteoclasts were identified by TRAP confocal fluorescence imaging. These key factors in osteoclast formation, such as (NFATc-1, c-Fos, V-ATPase-2 and CTSK), were investigated by Western blot. Results: Based on the above investigation, Lys-AuNCs were found to promote osteogenic differentiation and decrease osteoclast activity. It is noteworthy that the lysozyme (protected template), AuNPs, or the mixture of Lysozyme and AuNPs have negligible effects on osteoblastic differentiation compared to Lys-AuNCs. Conclusion: This study opens up a novel avenue to develop a new gold nanomaterial for promoting osteogenic differentiation. The possibility of using AuNCs as nanomedicines for the treatment of osteoporosis can be expected.


Assuntos
Nanopartículas Metálicas/química , Osteoclastos/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Animais , Diferenciação Celular/efeitos dos fármacos , Ouro/farmacologia , Nanopartículas Metálicas/administração & dosagem , Camundongos , Muramidase/química , Muramidase/metabolismo , Fatores de Transcrição NFATC/metabolismo , Nanomedicina/métodos , Osteoblastos/citologia , Osteoclastos/citologia , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-fos/metabolismo , Células RAW 264.7
4.
PLoS One ; 15(7): e0234964, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32614844

RESUMO

In this study, a facile, ecological and economical green method is described for the fabrication of iron (Fe), copper (Cu) and silver (Ag) nanoparticles (NPs) from the extract of Syzygium cumini leaves. The obtained metal NPs were categorized using UV/Vis, SEM, TEM, FTIR and EDX-ray spectroscopy techniques. The Fe-, Cu- and Ag-NPs were crystalline, spherical and size ranged from 40-52, 28-35 and 11-19 nm, respectively. The Ag-NPs showed excellent antimicrobial activities against methicillin- and vancomycin-resistance Staphylococcus aureus bacterial strains and Aspergillus flavus and A. parasiticus fungal species. Furthermore, the aflatoxins (AFs) production was also significantly inhibited when compared with the Fe- and Cu-NPs. In contrast, the adsorption results of NPs with aflatoxin B1 (AFB1) were observed as following order Fe->Cu->Ag-NPs. The Langmuir isotherm model well described the equilibrium data by the sorption capacity of Fe-NPs (105.3 ng mg-1), Cu-NPs (88.5 ng mg-1) and Ag-NPs (81.7 ng mg-1). The adsorption was found feasible, endothermic and follow the pseudo-second order kinetic model as revealed by the thermodynamic and kinetic studies. The present findings suggests that the green synthesis of metal NPs is a simple, sustainable, non-toxic, economical and energy-effective as compared to the others conventional approaches. In addition, synthesized metal NPs might be a promising AFs adsorbent for the detoxification of AFB1 in human and animal food/feed.


Assuntos
Aflatoxina B1/isolamento & purificação , Anti-Infecciosos/metabolismo , Biotecnologia/métodos , Cobre , Química Verde/métodos , Ferro , Nanopartículas Metálicas , Extratos Vegetais/metabolismo , Folhas de Planta/metabolismo , Prata , Desintoxicação por Sorção , Syzygium/metabolismo , Adsorção , Anti-Infecciosos/farmacologia , Aspergillus/efeitos dos fármacos , Aspergillus flavus/efeitos dos fármacos , Técnicas de Química Analítica , Cobre/administração & dosagem , Cobre/farmacologia , Resistência Microbiana a Medicamentos , Ferro/administração & dosagem , Ferro/farmacologia , Cinética , Nanopartículas Metálicas/administração & dosagem , Nanopartículas Metálicas/química , Nanopartículas Metálicas/ultraestrutura , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Oxirredução , Prata/administração & dosagem , Prata/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Termodinâmica , Vancomicina/farmacologia
5.
PLoS One ; 15(7): e0234916, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32614882

RESUMO

A great deal of attention has been focused on nanoparticles for cancer therapy, with the promise of tumor-selective delivery. However, despite intense work in the field over many years, the biggest obstacle to this vision remains extremely low delivery efficiency of nanoparticles into tumors. Due to the cost, time, and impact on the animals for in vivo studies, the nanoparticle field predominantly uses cellular uptake assays as a proxy to predict in vivo outcomes. Extensive research has focused on decreasing macrophage uptake in vitro as a proxy to delay nanoparticle accumulation in the mononuclear phagocytic system (MPS), mainly the liver and spleen, and thereby increase tumor accumulation. We have recently reported novel synthetic methods employing small molecule crosslinkers for the controlled assembly of small nanoparticles into larger aggregates and found that these nanoaggregates had remarkably high surface coverage and low cell uptake, even in macrophages. We further found that this extremely low cellular uptake could be recapitulated on solid gold nanoparticles by densely coating their surface with small molecules. Here we report our studies on the biodistribution and clearance of these materials in comparison to more conventional PEGylated gold nanoparticles. It was expected that the remarkably low macrophage uptake in vitro would translate to extended blood circulation time in vivo, but instead we found no correlation between either surface coverage or in vitro macrophage cell uptake and in vivo blood circulation. Gold nanoaggregates accumulate more rapidly and to a higher level in the liver compared to control gold nanoparticles. The lack of correlation between in vitro macrophage uptake and in vivo blood circulation suggests that the field must find other in vitro assays to use as a primary proxy for in vivo outcomes or use direct in vivo experimentation as a primary assay.


Assuntos
Materiais Revestidos Biocompatíveis/farmacocinética , Ouro/farmacocinética , Nanopartículas Metálicas , Polietilenoglicóis , Animais , Endocitose , Jejum/metabolismo , Feminino , Ouro/administração & dosagem , Ouro/sangue , Meia-Vida , Rim/metabolismo , Fígado/metabolismo , Macrófagos/fisiologia , Nanopartículas Metálicas/administração & dosagem , Nanopartículas Metálicas/classificação , Camundongos , Especificidade de Órgãos , Projetos Piloto , Células RAW 264.7 , Organismos Livres de Patógenos Específicos , Baço/metabolismo , Distribuição Tecidual
6.
Khirurgiia (Mosk) ; (5): 81-86, 2020.
Artigo em Russo | MEDLINE | ID: mdl-32500694

RESUMO

Increase of the frequency of soft tissues pyoinflammatory diseases and purulent-septic complications against the background the antibiotic-resistance of organism dictates the necessity of search of rational new surgical technologies and preparations with the intense bactericidal effect. Period of the connective tissue (cicatrix) formation on a place of wound defect of the operated purulent abscess of soft tissue (PAST) is defined by the speed of the granulations and epithelial tissue formation. Therefore, one of the task of experimental surgery is search of new methods of the effective postoperative influence on terms of the regeneration and complete obliteration of the PAST cavity. The perspective direction in treatment of surgical infection is application of metals nanoparticles. In treatment of pyoinflammatory processes it is applied the preparation Eplan and also zinc oxide nanoparticles which have bactericidal, antiinflammatory and regenerative effects. However, till now it was not carried out experimental works on modelling and surgical treatment of PAST with local application of the laser technologies in combinations with Eplan and metals nanoparticles.


Assuntos
Abscesso/terapia , Antibacterianos/uso terapêutico , Nanopartículas Metálicas/uso terapêutico , Infecções dos Tecidos Moles/terapia , Abscesso/tratamento farmacológico , Abscesso/cirurgia , Antibacterianos/administração & dosagem , Combinação de Medicamentos , Humanos , Terapia a Laser , Nanopartículas Metálicas/administração & dosagem , Pomadas/administração & dosagem , Pomadas/uso terapêutico , Infecções dos Tecidos Moles/tratamento farmacológico , Infecções dos Tecidos Moles/cirurgia , Supuração/tratamento farmacológico , Supuração/cirurgia , Supuração/terapia , Óxido de Zinco/administração & dosagem , Óxido de Zinco/uso terapêutico
7.
Int J Nanomedicine ; 15: 3827-3842, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32581533

RESUMO

Introduction: Copper oxide nanoparticles (CuO-NPs) are widely used as feed additives for livestock and poultry and implicated in many biomedical applications; however, overload of copper NPs induces various toxicological changes and dysfunction of animal's organs. Thus, this study was designed to evaluate the comparative toxicological effects of biologically and chemically synthesized CuO-NPs on mice. Methods: Transmission electron microscopy (TEM), X-ray diffraction (XRD) and Fourier-transform infrared spectroscopy (FT-IR) were used to characterize the sizes, shapes and functional groups of CuO-NPs. Forty-five mice were randomly allocated into three groups. Control group received distilled water. The second group was administered a single dose of biologically synthesized CuO-NPs (500 mg/kg bw) orally. The third group was administered a single dose of chemically synthesized CuO-NPs (500 mg/kg bw) orally. Results: TEM revealed that biologically synthesized NPs were spherical in shape, whereas chemically synthesized NPs were spherical or elongated in shape. XRD showed that the size of biologically synthesized NPs ranged from 4.14 to 12.82 nm and that of chemically synthesized NPs ranged from 4.06 to 26.82 nm. FT-IR spectroscopy indicated that the peaks appeared between 779 cm-1 and 425 cm-1 in biologically synthesized NPs and between 858 cm-1 and 524 cm-1 in chemically synthesized NPs were for Cu-O nanostructure. Four mice died due to administration of biologically synthesized CuO-NPs. Both biologically and chemically synthesized CuO-NPs induced leukocytosis, elevated serum activities of alanine aminotransferase and aspartate aminotransferase and serum levels of urea and creatinine and increased P53 mRNA and caspase-3 protein expressions in hepatic tissues. Moreover, CuO-NPs induced degenerative and necrotized changes in hepatic, renal and splenic tissues. Biochemical, apoptotic and pathological changes were more serious in mice administered with biologically synthesized CuO-NPs. Conclusion: This study indicated that a high dose of biologically and chemically synthesized CuO-NPs induced adverse effects on hepatic, renal and splenic tissues. At the same dose level, the biologically synthesized CuO-NPs evoked more potent toxic effects than the chemically synthesized CuO-NPs.


Assuntos
Cobre/toxicidade , Nanopartículas Metálicas/química , Nanopartículas Metálicas/toxicidade , Administração Oral , Animais , Caspase 3/metabolismo , Cobre/administração & dosagem , Rim/efeitos dos fármacos , Rim/patologia , Fígado/efeitos dos fármacos , Fígado/patologia , Masculino , Nanopartículas Metálicas/administração & dosagem , Camundongos , Microscopia Eletrônica de Transmissão , Nanopartículas , Espectroscopia de Infravermelho com Transformada de Fourier , Baço/efeitos dos fármacos , Baço/patologia , Ulva/metabolismo , Difração de Raios X
8.
Int J Nanomedicine ; 15: 3843-3850, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32581534

RESUMO

Purpose: Despite tremendous results achieved by immune checkpoint inhibitors, most patients are not responders, mainly because of the lack of a pre-existing anti-tumor immune response. Thus, solutions to efficiently prime this immune response are currently under intensive investigations. Radiotherapy elicits cancer cell death, generating an antitumor-specific T cell response, turning tumors in personalized in situ vaccines, with potentially systemic effects (abscopal effect). Nonetheless, clinical evidence of sustained anti-tumor immunity as abscopal effect are rare. Methods: Hafnium oxide nanoparticles (NBTXR3) have been designed to increase energy dose deposit within cancer cells. We examined the effect of radiotherapy-activated NBTXR3 on anti-tumor immune response activation and abscopal effect production using a mouse colorectal cancer model. Results: We demonstrate that radiotherapy-activated NBTXR3 kill more cancer cells than radiotherapy alone, significantly increase immune cell infiltrates both in treated and in untreated distant tumors, generating an abscopal effect dependent on CD8+ lymphocyte T cells. Conclusion: These data show that radiotherapy-activated NBTXR3 could increase local and distant tumor control through immune system priming. Our results may have important implications for immunotherapeutic agent combination with radiotherapy.


Assuntos
Antineoplásicos Imunológicos/farmacologia , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/radioterapia , Háfnio/farmacologia , Óxidos/farmacologia , Animais , Antineoplásicos Imunológicos/química , Antineoplásicos Imunológicos/farmacocinética , Disponibilidade Biológica , Linfócitos T CD8-Positivos/imunologia , Neoplasias Colorretais/imunologia , Feminino , Háfnio/química , Háfnio/farmacocinética , Nanopartículas Metálicas/administração & dosagem , Nanopartículas Metálicas/química , Camundongos Endogâmicos BALB C , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Experimentais/imunologia , Neoplasias Experimentais/radioterapia , Óxidos/química , Óxidos/farmacocinética
9.
Int J Nanomedicine ; 15: 2829-2839, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32368057

RESUMO

Objective: To investigate the remineralizing and staining effects of sodium fluoride (NaF) solution with polyethylene glycol-coated silver nanoparticles (PEG-AgNPs) on artificial dentine caries. Materials and Methods: Demineralized human dentine blocks were allocated to three groups. The blocks in group 1 underwent a topical application of a 12% silver diamine fluoride (SDF, 14,150 ppm fluoride) solution. The blocks in group 2 received a topical application of a 2.5% NaF (11,310 ppm fluoride) with PEG-AgNPs (400 ppm silver). The blocks in group 3 received deionized water. All blocks were subjected to pH cycling for 8 days. The surface morphology and cross-sectional features were investigated using scanning electron microscopy (SEM). The color parameters, crystal characteristics, lesion depth, and collagen degradation of the blocks were assessed using digital spectrophotometry, X-ray diffraction (XRD), micro-computed tomography, and spectrophotometry with a hydroxyproline assay, respectively. Results: The SEM showed that dentine collagen was exposed in group 3 but not in groups 1 and 2. The mean lesion depths in groups 1 to 3 were 118±7 µm, 121±14 µm, and 339±20 µm, respectively (groups1,2<3; p<0.001). The data indicated that fluoridated PEG-AgNPs introduced no significant color effect on dentine, but SDF caused distinct discoloration. The XRD indicated that silver chloride was formed in group 1, and fluorapatite was detected in groups 1 and 2. The concentration of hydroxyproline liberated from collagen was significantly less in groups 1 and 2 than in group 3. Conclusion: The use of NaF solution with PEG-AgNPs can remineralize artificial dentine caries and inhibit collagen degradation without causing significant tooth staining.


Assuntos
Cárie Dentária/tratamento farmacológico , Dentina/efeitos dos fármacos , Nanopartículas Metálicas/uso terapêutico , Fluoreto de Sódio/farmacologia , Remineralização Dentária/métodos , Colágeno , Cor , Dentina/metabolismo , Dentina/patologia , Fluoretos/farmacologia , Fluoretos Tópicos/química , Fluoretos Tópicos/farmacologia , Humanos , Hidroxiprolina/metabolismo , Nanopartículas Metálicas/administração & dosagem , Nanopartículas Metálicas/química , Microscopia Eletrônica de Varredura , Dente Serotino/efeitos dos fármacos , Dente Serotino/patologia , Dente Serotino/ultraestrutura , Polietilenoglicóis/química , Compostos de Amônio Quaternário/química , Compostos de Amônio Quaternário/farmacologia , Prata , Compostos de Prata/química , Compostos de Prata/farmacologia , Fluoreto de Sódio/administração & dosagem , Difração de Raios X , Microtomografia por Raio-X
10.
Cancer Immunol Immunother ; 69(9): 1833-1840, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32350593

RESUMO

BACKGROUND: Bladder cancer is diagnosed by the use of several biomarkers, including survivin. This protein has an important role in the cancer progression by controlling the rate of cell apoptosis. Findings show that there is no survivin in normal tissues, whereas the level of survivin expression increases in tumor cells. DESIGN: The purpose of this study was to specify the reactive antibodies to survivin protein as a biomarker to determine the bladder cancer stage with ELISA method and using GNPs conjugated with survivin antibody. The serum and urine samples of patients with bladder cancer were collected among those referred to Sina Hospital, Tehran, Iran. The survivin protein level was measured in the serum and urine by ELISA technique and in the urine by GNPs conjugated with survivin. RESULTS: Based on the results of ELISA, the serum and urinary levels of survivin increased significantly in T3 and T4 stages of the disease (high grades), compared with the healthy individuals. Also, using conjugated GNPs, survivin protein was detected in the urine specimens of patients at all grades (low and high grades). CONCLUSION: Our findings showed that using the ELISA technique, the increased level of survivin could be identified in high grades of bladder cancer, but using anti-survivin antibody-conjugated GNPs, bladder cancer can be detected in early stages. The applied method was found to be a rapid tool, dependent on visible color changes and colorimetric detection, without any need for reader devices.


Assuntos
Anticorpos/metabolismo , Ouro/administração & dosagem , Nanopartículas Metálicas/administração & dosagem , Survivina/metabolismo , Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias da Bexiga Urinária/metabolismo , Biomarcadores Tumorais/metabolismo , Feminino , Humanos , Masculino , Sensibilidade e Especificidade , Ressonância de Plasmônio de Superfície/métodos
11.
Exp Parasitol ; 215: 107915, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32461112

RESUMO

Acanthamoeba castellanii is an opportunistic protozoan responsible for serious human infections including Acanthamoeba keratitis and granulomatous amoebic encephalitis. Despite advances in antimicrobial therapy and supportive care, infections due to Acanthamoeba are a major public concern. Current methods of treatment are not fully effective against both the trophozoite and cyst forms of A. castellanii and are often associated with severe adverse effects, host cell cytotoxicity and recurrence of infection. Therefore, there is an urgent need to develop new therapeutic approaches for the treatment and management of Acanthamoebic infections. Repurposing of clinically approved drugs is a viable avenue for exploration and is particularly useful for neglected and rare diseases where there is limited interest by pharmaceutical companies. Nanotechnology-based drug delivery systems offer promising approaches in the biomedical field, particularly in diagnosis and drug delivery. Herein, we conjugated an antihyperglycemic drug, metformin with silver nanoparticles and assessed its anti-acanthamoebic properties. Characterization by ultraviolet-visible spectrophotometry and atomic force microscopy showed successful formation of metformin-coated silver nanoparticles. Amoebicidal and amoebistatic assays revealed that metformin-coated silver nanoparticles reduced the viability and inhibited the growth of A. castellanii significantly more than metformin and silver nanoparticles alone at both 5 and 10 µM after 24 h incubation. Metformin-coated silver nanoparticles also blocked encystation and inhibited the excystation in Acanthamoeba after 72 h incubation. Overall, the conjugation of metformin with silver nanoparticles was found to enhance its antiamoebic effects against A. castellanii. Furthermore, the pretreatment of A. castellanii with metformin and metformin-coated silver nanoparticles for 2 h also reduced the amoebae-mediated host cell cytotoxicity after 24 h incubation from 73% to 10% at 10 µM, indicating that the drug-conjugated silver nanoparticles confer protection to human cells. These findings suggest that metformin-coated silver nanoparticles hold promise in the improved treatment and management of Acanthamoeba infections.


Assuntos
Acanthamoeba castellanii/efeitos dos fármacos , Metformina/administração & dosagem , Ceratite por Acanthamoeba/tratamento farmacológico , Ceratite por Acanthamoeba/parasitologia , Anti-Infecciosos Locais/farmacologia , Infecções Protozoárias do Sistema Nervoso Central/tratamento farmacológico , Infecções Protozoárias do Sistema Nervoso Central/parasitologia , Clorexidina/farmacologia , Células HeLa , Humanos , Encefalite Infecciosa/tratamento farmacológico , Encefalite Infecciosa/parasitologia , Nanopartículas Metálicas/administração & dosagem , Nanopartículas Metálicas/uso terapêutico , Metformina/farmacologia , Metformina/uso terapêutico , Microscopia de Força Atômica , Encistamento de Parasitas/efeitos dos fármacos , Prata , Espectrofotometria Ultravioleta , Trofozoítos/efeitos dos fármacos
12.
Braz J Med Biol Res ; 53(5): e8457, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32348428

RESUMO

The objective of this study was to investigate whether the conjugation of gold nanoparticles (GNPs) to 5-aminolevulinic acid (5-ALA) could enhance the anti-tumor efficiency of photodynamic therapy (PDT) in epidermoid carcinoma cells. The mRNA and protein expression levels were determined by quantitative real-time PCR and western blot, respectively. Cell viability, apoptosis, invasion, and migration were determined by MTT assay, flow cytometry, transwell invasion assay, and migration assay, respectively. Singlet oxygen generation was detected by the singlet oxygen sensor green reagent assay. Our results showed that PDT with 5-ALA and GNPs-conjugated 5-ALA (5-ALA-GNPs) significantly suppressed cell viability, increased cell apoptosis and singlet oxygen generation in both HaCat and A431 cells, and PDT with 5-ALA and 5-ALA-GNPs had more profound effects in A431 cells than that in HaCat cells. More importantly, 5-ALA-GNPs treatment potentiated the effects of PDT on cell viability, cell apoptosis, and singlet oxygen generation in A431 cells compared to 5-ALA treatment. Further in vitro assays showed that PDT with 5-ALA-GNPs significantly decreased expression of STAT3 and Bcl-2 and increased expression of Bax in A431 cells compared with PDT with 5-ALA. In addition, 5-ALA-GNPs treatment enhanced the inhibitory effects of PDT on cell invasion and migration and Wnt/ß-catenin signaling activities in A431 cells compared to 5-ALA treatment. In conclusion, our results suggested that GNPs conjugated to 5-ALA significantly enhanced the anti-tumor efficacy of PDT in A431 cells, which may represent a better strategy to improve the outcomes of patients with cutaneous squamous cell carcinoma.


Assuntos
Carcinoma de Células Escamosas/patologia , Ácidos Levulínicos/farmacologia , Nanopartículas Metálicas/administração & dosagem , Fotoquimioterapia , Neoplasias Cutâneas/patologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Humanos , RNA Neoplásico
13.
Chem Commun (Camb) ; 56(35): 4852-4855, 2020 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-32236262

RESUMO

Detection of chemical reactions in living cells is critical in understanding physiological metabolic processes in the context of nanomedicine. Carbon monoxide (CO) is one of the important gaseous signaling molecules. Surface-enhanced Raman spectroscopy (SERS)-based CO-releasing nanoparticles (CORN) is utilized to investigate the chemical reaction of CO delivery in live cells. Using SERS CORN, carbonyl dissociation from CORN-Ag-CpW(CO)3 to CORN-Ag-CpW(CO)2 in live cells is observed. The subsequent irreversible degradation to CO-free CORN is a consequence of oxidative stress in cells. This observation affirms the step transition of CORN-Ag-CpW(CO)3 in cellular: CORN-Ag-CpW(CO)3 first proceeds via a direct loss of one CO followed by a oxidative decomposition giving rise to CORN-Ag-WO3 and as well as the release of one equivalents of CO. Importantly, the decarbonylation process can be correlated with the level of inflammatory biomarkers. For the first time, we provide unambiguous evidence for the steps transition of CO-release mechanism in cellular.


Assuntos
Monóxido de Carbono/metabolismo , Nanopartículas Metálicas/administração & dosagem , Prata/administração & dosagem , Tungstênio/administração & dosagem , Animais , Linhagem Celular , Citocinas/metabolismo , Humanos , Camundongos , Análise Espectral Raman
14.
Int J Nanomedicine ; 15: 2011-2026, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32273699

RESUMO

Introduction: The bone regeneration of endosseous implanted biomaterials is often impaired by the host immune response, especially macrophage-related inflammation which plays an important role in the bone healing process. Thus, it is a promising strategy to design an osteo-immunomodulatory biomaterial to take advantage of the macrophage-related immune response and improve the osseointegration performance of the implant. Methods: In this study, we developed an antibacterial silver nanoparticle-loaded TiO2 nanotubes (Ag@TiO2-NTs) using an electrochemical anodization method to make the surface modification and investigated the influences of Ag@TiO2-NTs on the macrophage polarization, osteo-immune microenvironment as well as its potential molecular mechanisms in vitro and in vivo. Results: The results showed that Ag@TiO2-NTs with controlled releasing of ultra-low-dose Ag+ ions had the excellent ability to induce the macrophage polarization towards the M2 phenotype and create a suitable osteo-immune microenvironment in vitro, via inhibiting PI3K/Akt, suppressing the downstream effector GLUT1, and activating autophagy. Moreover, Ag@TiO2-NTs surface could improve bone formation, suppress inflammation, and promote osteo-immune microenvironment compared to the TiO2-NTs and polished Ti surfaces in vivo. These findings suggested that Ag@TiO2-NTs with controlled releasing of ultra-low-dose Ag+ ions could not only inhibit the inflammation process but also promote the bone healing by inducing healing-associated M2 polarization. Discussion: Using this surface modification strategy to modulate the macrophage-related immune response, rather than prevent the host response, maybe a promising strategy for implant surgeries in the future.


Assuntos
Autofagia/efeitos dos fármacos , Transportador de Glucose Tipo 1/metabolismo , Fatores Imunológicos/administração & dosagem , Macrófagos/efeitos dos fármacos , Nanopartículas Metálicas/administração & dosagem , Prata/farmacocinética , Animais , Antibacterianos/farmacocinética , Antibacterianos/farmacologia , Materiais Biocompatíveis/química , Técnicas Eletroquímicas , Transportador de Glucose Tipo 1/genética , Fatores Imunológicos/imunologia , Masculino , Nanopartículas Metálicas/química , Camundongos , Nanotubos/química , Osseointegração/efeitos dos fármacos , Osteoblastos/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/metabolismo , Próteses e Implantes , Células RAW 264.7 , Ratos Sprague-Dawley , Prata/química , Tíbia/diagnóstico por imagem , Tíbia/cirurgia , Titânio/química , Cicatrização/efeitos dos fármacos
15.
Int J Nanomedicine ; 15: 1457-1468, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32184598

RESUMO

Purpose: Zinc oxide nanoparticles (nZnO) have been widely used in the medicine field. Numerous mechanistic studies for nZnO's anticancer effects are merely performed under high concentration exposure. However, possible anticancer mechanisms of epigenetic dysregulation induced by low doses of nZnO are unclear. Methods: nZnO were characterized and bladder cancer T24 cells were treated with nZnO for 48 hrs at different exposure concentrations. Cell cycle, apoptosis, cell migration and invasion were determined. We performed qRT-PCR, Western blot and chromatin immunoprecipitation to detect the mRNA and protein levels of signaling pathway cascades for histone modification. Results: In this study, we investigated the potential anticancer effects and mechanisms of nZnO on histone modifications in bladder cancer T24 cells upon low-dose exposure. Our findings showed that low concentrations of nZnO resulted in cell cycle arrest at S phase, facilitated cellular late apoptosis, repressed cell invasion and migration after 48 hrs exposure. These anticancer effects could be attributed to increased RUNX3 levels resulting from reduced H3K27me3 occupancy on the RUNX3 promoter, as well as decreased contents of histone methyltransferase EZH2 and the trimethylation of histone H3K27. Our findings reveal that nZnO are able to enter into the cytoplasm and nucleus of T24 cells. Additionally, both particles and ions from nZnO may jointly contribute to the alteration of histone methylation. Moreover, sublethal nZnO-conducted anticancer effects and epigenetic mechanisms were not associated with oxidative stress or DNA damage. Conclusion: We reveal a novel epigenetic mechanism for anticancer effects of nZnO in bladder cancer cells under low-dose exposure. This study will provide experimental basis for the toxicology and cancer therapy of nanomaterials.


Assuntos
Antineoplásicos/farmacologia , Metilação de DNA/efeitos dos fármacos , Histonas/metabolismo , Nanopartículas Metálicas/uso terapêutico , Neoplasias da Bexiga Urinária/tratamento farmacológico , Óxido de Zinco/farmacologia , Antineoplásicos/administração & dosagem , Linhagem Celular Tumoral , Subunidade alfa 3 de Fator de Ligação ao Core/genética , Subunidade alfa 3 de Fator de Ligação ao Core/metabolismo , Relação Dose-Resposta a Droga , Epigênese Genética/efeitos dos fármacos , Humanos , Lisina/metabolismo , Nanopartículas Metálicas/administração & dosagem , Nanopartículas Metálicas/química , Estresse Oxidativo/efeitos dos fármacos , Regiões Promotoras Genéticas , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/metabolismo , Óxido de Zinco/administração & dosagem
16.
Artigo em Inglês | MEDLINE | ID: mdl-32167009

RESUMO

Silver nanoparticles (AgNPs) have been widely used for a multitude of applications without full comprehensive knowledge regarding their safety. In particular, lack of data on hazard characterization may lead to uncertainties regarding potential human health risk. To provide the foundation for human health risk assessment of AgNPs, this study evaluates existing hazard characterization data, including reported pharmacokinetics, symptoms, and their corresponding dose-response relationships. Human equivalent relationships are also provided by extrapolation from animal dose-response relationships. From the data analyzed, it appears that AgNPs may persist for long periods (from days to years) in the human body. It was found that AgNP toxicity on traditional major targets of exogenous substances were generally underestimated. Some omissions of toxicity on sensitive systems in the AgNP toxicity assessment require attention, such as reprotoxicity and neurotoxicity. The necessity of the establishment of toxicity tests specifically for nanomaterials is highlighted. The scientific basis of a toxicity testing strategy is advised by this study, which paves the way for the monitoring and regulation of the ENP utilization in various industries.


Assuntos
Exposição Ambiental/efeitos adversos , Substâncias Perigosas/toxicidade , Nanopartículas Metálicas/toxicidade , Prata/toxicidade , Administração Cutânea , Administração Oral , Animais , Exposição Ambiental/análise , Substâncias Perigosas/administração & dosagem , Substâncias Perigosas/química , Substâncias Perigosas/farmacocinética , Humanos , Exposição por Inalação , Injeções Intravenosas , Injeções Subcutâneas , Nanopartículas Metálicas/administração & dosagem , Nanopartículas Metálicas/química , Especificidade de Órgãos , Prata/administração & dosagem , Prata/química , Prata/farmacocinética , Distribuição Tecidual , Testes de Toxicidade
17.
Int J Nanomedicine ; 15: 1499-1515, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32189965

RESUMO

Purpose: Some chemotherapeutics have been shown to induce both the release of damage-associated molecular patterns (DAMPs) and the production of type I interferon (IFN-I), leading to immunogenic cell death (ICD). However, the standard chemotherapy drug for glioma, temozolomide (TMZ), cannot induce ICD as it cannot activate IFN-I signaling. Moreover, inefficient delivery of immunostimulants across the blood-brain barrier (BBB) is the main obstacle to overcome in order to induce local immune responses in the brain. Methods: A new oligonucleotide nanoformulation (Au@PP)/poly(I:C)) was constructed by coating gold nanoparticles (AuNPs) with methoxypolyethylene glycol (mPEG)-detachable (d)-polyethyleneimine (PEI) (Au@PP) followed by inducing the formation of electrostatic interactions with polyinosinic-polycytidylic acid (poly(I:C)). Intracranial GL261 tumor-bearing C57BL/6 mice were used to explore the therapeutic outcomes of Au@PP/poly(I:C) plus TMZ in vivo. The anti-tumor immune response in the brain induced by this treatment was analyzed by RNA sequencing and immunohistochemical analyses. Results: Au@PP/poly(I:C) induced IFN-I production after endocytosis into glioma cells in vitro. Additionally, Au@PP/poly(I:C) was efficiently accumulated in the glioma tissue after intranasal administration, which allowed the nanoformulation to enter the brain while bypassing the BBB. Furthermore, Au@PP/poly(I:C) plus TMZ significantly improved the overall survival of the tumor-bearing mice compared with group TMZ only. RNA sequencing and immunohistochemical analyses revealed efficient immune response activation and T lymphocyte infiltration in the Au@PP/poly(I:C) plus TMZ group. Conclusion: This study demonstrates that intranasal administration of Au@PP/poly(I:C) combined with TMZ induces ICD, thereby stimulating an in situ immune response to inhibit glioma growth.


Assuntos
Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/imunologia , Glioma/tratamento farmacológico , Glioma/imunologia , Nanopartículas Metálicas/administração & dosagem , Nanopartículas Metálicas/uso terapêutico , Administração Intranasal , Animais , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sistemas de Liberação de Medicamentos , Feminino , Ouro/uso terapêutico , Humanos , Interferon Tipo I/metabolismo , Nanopartículas Metálicas/ultraestrutura , Camundongos , Camundongos Endogâmicos C57BL , Poli I-C/síntese química , Poli I-C/química , Polietilenoglicóis/síntese química , Polietilenoglicóis/química , Polietilenoimina/síntese química , Polietilenoimina/química , Análise de Sobrevida , Linfócitos T/efeitos dos fármacos , Temozolomida/farmacologia , Temozolomida/uso terapêutico
18.
Int J Nanomedicine ; 15: 1363-1372, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32184591

RESUMO

Purpose: In this study, we constructed novel brain-targeting complexes (U2-AuNP) by conjugating aptamer U2 to the gold nanoparticle (AuNPs) surface as a promising option for GBM therapy. Materials and Methods: The properties of the U2-AuNP complexes were thoroughly characterized. Then, we detected the in vitro effects of U2-AuNP in U87-EGFRvIII cell lines and the in vivo antitumor effects of U2-AuNP in GBM-bearing mice. Furthermore, we explored the inhibition mechanism of U2-AuNP in U87-EGFRvIII cell lines. Results: We found that U2-AuNP inhibits the proliferation and invasion of U87-EGFRvIII cell lines and prolongs the survival time of GBM-bearing mice. We found that U2-AuNP can inhibit the EGFR-related pathway and prevent DNA damage repair in GBM cells. Conclusion: These results reveal the promising potential of U2-AuNP as a drug candidate for targeted therapy in GBM.


Assuntos
Antineoplásicos/farmacologia , Aptâmeros de Nucleotídeos/farmacologia , Neoplasias Encefálicas/tratamento farmacológico , Receptores ErbB/antagonistas & inibidores , Glioblastoma/tratamento farmacológico , Ouro/química , Nanopartículas Metálicas/administração & dosagem , Animais , Antineoplásicos/química , Apoptose , Aptâmeros de Nucleotídeos/química , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Proliferação de Células , Glioblastoma/genética , Glioblastoma/metabolismo , Glioblastoma/patologia , Humanos , Masculino , Nanopartículas Metálicas/química , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
19.
Int J Nanomedicine ; 15: 1373-1385, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32184592

RESUMO

Background: Photothermal therapy (PTT) has great potential application in the treatment of tumors. However, due to the low penetration of near-infrared light (NIR) and the low concentration of nanomaterials in the tumor site, the application of PTT has been limited. Purpose: The objective of this study was to investigate the therapeutic effect of transcatheter intra-arterial infusion of lecithin-modified Bi nanoparticles (Bi-Ln NPs) combined with interventional PTT (IPTT) on hepatocellular carcinoma. Methods: Bi-Ln NPs were prepared by emulsifying the hydrophobic Bi nanoparticles and lecithin, and the photothermal conversion and cytotoxicity of Bi-Ln NPs were then measured by infrared imaging and MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay, respectively. Twenty-four VX2 hepatic carcinoma rabbits were randomly divided into four groups. Rabbits in group A received Bi-Ln NPs by intra-arterial infusion and NIR laser treatment (IA Bi-Ln NPs + Laser), group B received Bi-Ln NPs by intravenous infusion and NIR laser treatment (IV Bi-Ln NPs + Laser), group C received PBS (phosphate buffer saline) via intra-arterial infusion with NIR laser treatment (IA PBS + Laser), group D received PBS via intra-arterial infusion (IA PBS). Transcatheter intra-arterial infusion was conducted by superselective intubation under digital subtraction angiography (DSA) guidance. IPTT was performed by introducing an NIR optical fiber access to the rabbit VX2 hepatic carcinoma under real-time ultrasound guidance. Magnetic resonance imaging (MRI) was performed to evaluate the tumor size. Hematoxylin and eosin (H&E) stain and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) were conducted 7 days after treatment to evaluate the necrosis rate and viability of tumor, respectively. Results: The Bi-Ln NPs have the advantages of good biological compatibility and high photothermal conversion efficiency. Minimally invasive transcatheter intra-arterial infusion can markedly increase the concentration of Bi-Ln NPs in tumor tissues. IPTT can contribute to the significant improvement in the photothermal efficiency of Bi-Ln NPs. Compared to other groups, the group of IA Bi-Ln NPs + Laser showed a significantly higher tumor inhibition rate (TIR) of 93.38 ± 19.57%, a higher tumor necrosis rate of 83.12 ± 8.02%, and a higher apoptosis rate of (43.26 ± 10.65%) after treatment. Conclusion: Transcatheter intra-arterial infusion combined with interventional PTT (IPTT) is safe and effective in eradicating tumor cells and inhibiting tumor growth and may provide a novel and valuable choice for the treatment of hepatocellular carcinoma in the future.


Assuntos
Bismuto/química , Carcinoma Hepatocelular/terapia , Neoplasias Hepáticas Experimentais/terapia , Nanopartículas Metálicas/administração & dosagem , Fototerapia , Ultrassonografia/métodos , Animais , Apoptose , Carcinoma Hepatocelular/patologia , Terapia Combinada , Feminino , Artéria Hepática , Raios Infravermelhos , Infusões Intra-Arteriais , Lecitinas/química , Neoplasias Hepáticas Experimentais/patologia , Masculino , Nanopartículas Metálicas/química , Necrose , Coelhos
20.
Life Sci ; 252: 117571, 2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32201278

RESUMO

AIMS: Nanoparticles (NPs) exposure is associated with increased risk of cardiovascular diseases, but the underlying mechanism is still obscure. In this study, we investigated the role of NADPH oxidase 4 (NOX4) in copper oxide nanoparticles (CuONPs)-induced cytotoxicity in human umbilical vein endothelial cells (HUVECs). MATERIALS AND METHODS: Morphology changes were examined under the microscope. Cell viability was determined by MTS assay and Calcein AM assay. Apoptosis and the levels of superoxide anion (O2-) and hydrogen peroxide (H2O2) were measured by fluorescence activated cell sorting (FACS). Oxidative stress was detected by assaying the levels of glutathione/glutathione disulfide (GSH/GSSG) and malondialdehyde (MDA). Protein expression levels were determined by western blotting. KEY FINDINGS: We revealed that O2- rather than H2O2 was the major component of reactive oxygen species (ROS) in CuONPs-treated HUVECs. Meanwhile, CuONPs downregulated expression of O2--eliminating enzyme NOX4 both at mRNA and protein levels, but did not affect the expression of SOD2 and catalase. NOX4 knockdown caused more accumulation of O2-, and a further decrease of H2O2 in CuONPs-treated HUVECs, suggesting that NOX4 regulates the conversion of O2- to H2O2 in CuONPs-treated HUVECs. Furthermore, we revealed that NOX4 knockdown aggravated CuONPs-induced oxidative stress, characterized by a decrease of GSH/GSSG ratio, an increase of MDA level, and upregulation of HSPA5 and γH2AX. Finally, we showed that NOX4 knockdown exacerbated CuONPs-induced apoptotic cell death in HUVECs, indicating that NOX4 could protect ECs from CuONPs-induced cell death. SIGNIFICANCE: Our study provides the evidence that NOX4 protects vascular endothelial cells from CuONPs-induced oxidative stress and cell death.


Assuntos
Cobre/química , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Nanopartículas Metálicas/toxicidade , NADPH Oxidase 4/genética , Estresse Oxidativo/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Catalase/metabolismo , Morte Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Técnicas de Silenciamento de Genes , Humanos , Peróxido de Hidrogênio/metabolismo , Malondialdeído/metabolismo , Nanopartículas Metálicas/administração & dosagem , Espécies Reativas de Oxigênio/metabolismo
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