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1.
NanoImpact ; 35: 100517, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38848992

RESUMO

Superparamagnetic iron oxide nanoparticles (SPIONs) have gained significant attention in biomedical research due to their potential applications. However, little is known about their impact and toxicity on testicular cells. To address this issue, we conducted an in vitro study using primary mouse testicular cells, testis fragments, and sperm to investigate the cytotoxic effects of sodium citrate-coated SPIONs (Cit_SPIONs). Herein, we synthesized and physiochemically characterized the Cit_SPIONs and observed that the sodium citrate diminished the size and improved the stability of nanoparticles in solution during the experimental time. The sodium citrate (measured by thermogravimetry) was biocompatible with testicular cells at the used concentration (3%). Despite these favorable physicochemical properties, the in vitro experiments demonstrated the cytotoxicity of Cit_SPIONs, particularly towards testicular somatic cells and sperm cells. Transmission electron microscopy analysis confirmed that Leydig cells preferentially internalized Cit_SPIONs in the organotypic culture system, which resulted in alterations in their cytoplasmic size. Additionally, we found that Cit_SPIONs exposure had detrimental effects on various parameters of sperm cells, including motility, viability, DNA integrity, mitochondrial activity, lipid peroxidation (LPO), and ROS production. Our findings suggest that testicular somatic cells and sperm cells are highly sensitive and vulnerable to Cit_SPIONs and induced oxidative stress. This study emphasizes the potential toxicity of SPIONs, indicating significant threats to the male reproductive system. Our findings highlight the need for detailed development of iron oxide nanoparticles to enhance reproductive nanosafety.


Assuntos
Nanopartículas Magnéticas de Óxido de Ferro , Espermatozoides , Testículo , Masculino , Animais , Camundongos , Testículo/efeitos dos fármacos , Nanopartículas Magnéticas de Óxido de Ferro/toxicidade , Nanopartículas Magnéticas de Óxido de Ferro/química , Espermatozoides/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Intersticiais do Testículo/efeitos dos fármacos , Células Intersticiais do Testículo/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Citrato de Sódio , Células Cultivadas
2.
J Dairy Sci ; 107(5): 2681-2689, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-37923204

RESUMO

The potential use of carbon-based methodologies for drug delivery and reproductive biology in cows raises concerns about residues in milk and food safety. This study aimed to assess the potential of Fourier transform Raman spectroscopy and discriminant analysis using partial least squares (PLS-DA) to detect functionalized multiwalled carbon nanotubes (MWCNT) in bovine raw milk. Oxidized MWCNT were diluted in milk at different concentrations from 25.00 to 0.01 µg/mL. Raman spectroscopy measurements and PLS-DA were performed to identify low concentrations of MWCNT in milk samples. The PLS-DA model was characterized by the analysis of the variable importance in projection (VIP) scores. All the training samples were correctly classified by the model, resulting in no false-positive or false-negative classifications. For test samples, only one false-negative result was observed, for 0.01 µg/mL MWCNT dilution. The association between Raman spectroscopy and PLS-DA was able to identify MWCNT diluted in milk samples up to 0.1 µg/mL. The PLS-DA model was built and validated using a set of test samples and spectrally interpreted based on the highest VIP scores. This allowed the identification of the vibrational modes associated with the D and G bands of MWCNT, as well as the milk bands, which were the most important variables in this analysis.

3.
Nanotechnology ; 33(6)2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34700304

RESUMO

Carboxylated multi-wall carbon nanotube (MWCNT-COOH) presents unique properties due to nanoscale dimensions and permits a broad range of applications in different fields, such as bone tissue engineering and regenerative medicine. However, the cytocompatibility of MWCNT-COOH with human stem cells is poorly understood. Thus, studies elucidating how MWCNT-COOH affects human stem cell viability are essential to a safer application of nanotechnologies. Using stem cells from the human exfoliated deciduous teeth model, we have evaluated the effects of MWCNT-COOH on cell viability, oxidative cell stress, and DNA integrity. Results demonstrated that despite the decreased metabolism of mitochondria, MWCNT-COOH had no toxicity against stem cells. Cells maintained viability after MWCNT-COOH exposure. MWCNT-COOH did not alter the superoxide dismutase activity and did not cause genotoxic effects. The present findings are relevant to the potential application of MWCNT-COOH in the tissue engineering and regenerative medicine fields.


Assuntos
Nanomedicina , Nanotubos de Carbono/toxicidade , Células-Tronco , Engenharia Tecidual , Dente Decíduo/citologia , Ácidos Carboxílicos/toxicidade , Sobrevivência Celular/efeitos dos fármacos , Humanos , Células-Tronco/citologia , Células-Tronco/efeitos dos fármacos
4.
J Mater Chem B ; 9(5): 1414-1423, 2021 02 07.
Artigo em Inglês | MEDLINE | ID: mdl-33464273

RESUMO

Flow cytometry is a universally applied technique in many biological and clinical assays to evaluate cells, bacteria, parasites, and particles at a micrometre scale. More advanced flow cytometers can detect small molecules down to the nanometre scale that may identify intracellular nanostructures. Advancements in the field of nanobiotechnology have led to techniques that allow the study of cellular behaviour after exposure to nanomaterials, particularly, metal nanoparticles. The optical properties of gold nanoparticles regarding surface plasmon resonance (SPR) are established to increase the fluorescence quantum yields of several dyes working as optical antennas, enabling the enhancement of light emission in fluorescent emitters. In this work we constructed a nanoprobe using gold nanoparticles coated with primary antibody Cetuximab. Then, we investigated whether this nanoprobe labelled with secondary fluorescent antibody Alexa Fluor 488, at low concentrations, could promote fluorescent signal enhancement, associated with SPR, and detected by the flow cytometry technique. Our results showed an enhanced fluorescent signal likely due to the proximity between the extinction coefficient of gold nanoparticles and the emission peak of Alexa Fluor 488, at exceptionally low concentrations, occurring within a high level of specificity. Moreover, the nanoprobe did not alter the cellular viability suggesting gold nanoparticles as a feasible approach for cell labelling using low concentrations of secondary antibodies for routine flow cytometry applications.


Assuntos
Anticorpos/química , Citometria de Fluxo/métodos , Corantes Fluorescentes/química , Ouro/química , Nanopartículas Metálicas/química , Humanos
5.
Nat Prod Res ; 35(22): 4694-4697, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31894699

RESUMO

The investigation of the effects of three essential oils (EOs) from Taxandria fragrans (FRA), Melaleuca alternifolia (TTO) and Boswellia serrata (IF), alone and combined with ketoconazole (KTZ), and their functionalised gold nanoparticles (AuNP) against Trichophyton interdigitale both in vitro and in vivo indicated that EOs presented activity against T. interdigitale. The combination of EOs and KTZ was antagonistic. FRA, TTO, gold nanoparticles capped with T. fragrans (AuNPFRA) and gold nanoparticles capped with M. alternifolia (AuNPTTO) presented antidermatophytic activity in vivo, with the capacity to reduce fungal burden and to preserve tissue architecture; however, combination treatment with KTZ increased fungal burden and caused tissue damage. The combination of EO with KTZ exhibited antagonistic activity and was histologically harmful. In contrast, FRA, TTO, AuNPFRA and AuNPTTO are promising treatments for dermatophytosis.


Assuntos
Melaleuca , Nanopartículas Metálicas , Nanosferas , Óleos Voláteis , Arthrodermataceae , Ouro , Cetoconazol/farmacologia , Óleos Voláteis/farmacologia
6.
Biomed Pharmacother ; 134: 111120, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33341671

RESUMO

Visceral leishmaniasis (VL) is a systemic parasitic disease that leads to high rates of morbidity and mortality in humans worldwide. There is a great need to develop new drugs and novel strategies to make chemotherapy for this disease more efficacious and well tolerated. Recent reports on the immunomodulatory effects and the low toxicity of the spherical carbon nanostructure fullerol led us to investigate in vitro and in vivo antileishmanial activity in free and encapsulated forms in liposomes. When assayed against intramacrophagic Leishmania amastigotes, fullerol showed a dose-dependent reduction of the infection index with IC50 of 0.042 mg/mL. When given daily by i.p. route for 20 days (0.05 mg/kg/d) in a murine model of acute VL, fullerol promoted significant reduction in the liver parasite load. To improve the delivery of fullerol to the infection sites, liposomal formulations were prepared by the dehydration-rehydration method. When evaluated in the acute VL model, liposomal fullerol (Lip-Ful) formulations given i.p. at 0.05 and 0.2 mg/kg with 4-days intervals were more effective than the free form, with significant parasite reductions in both liver and spleen. Lip-Ful at 0.2 mg/kg promoted complete parasite elimination in the liver. The antileishmanial activity of Lip-Ful was further confirmed in a chronic model of VL. Lip-Ful was also found to induce secretion of pro-inflammatory TNF-α, IFN-γ and IL-1ß cytokines. In conclusion, this work reports for the first time the antileishmanial activity of fullerol and introduces an innovative approach for treatment of VL based on the association of this nanostructure with liposomes.


Assuntos
Fulerenos/farmacologia , Leishmania infantum/efeitos dos fármacos , Leishmania mexicana/efeitos dos fármacos , Leishmaniose Visceral/tratamento farmacológico , Lipídeos/química , Fígado/parasitologia , Macrófagos Peritoneais/parasitologia , Tripanossomicidas/farmacologia , Animais , Citocinas/sangue , Modelos Animais de Doenças , Composição de Medicamentos , Feminino , Fulerenos/química , Mediadores da Inflamação/sangue , Leishmania infantum/crescimento & desenvolvimento , Leishmania mexicana/crescimento & desenvolvimento , Leishmaniose Visceral/sangue , Leishmaniose Visceral/parasitologia , Lipossomos , Fígado/metabolismo , Mesocricetus , Camundongos Endogâmicos BALB C , Nanopartículas , Carga Parasitária , Tripanossomicidas/química
7.
Sci Rep ; 10(1): 11302, 2020 07 09.
Artigo em Inglês | MEDLINE | ID: mdl-32647259

RESUMO

The Flaviviridae virus family was named after the Yellow-fever virus, and the latin term flavi means "of golden color". Dengue, caused by Dengue virus (DENV), is one of the most important infectious diseases worldwide. A sensitive and differential diagnosis is crucial for patient management, especially due to the occurrence of serological cross-reactivity to other co-circulating flaviviruses. This became particularly important with the emergence of Zika virus (ZIKV) in areas were DENV seroprevalence was already high. We developed a sensitive and specific diagnostic test based on gold nanorods (GNR) functionalized with DENV proteins as nanosensors. These were able to detect as little as one picogram of anti-DENV monoclonal antibodies and highly diluted DENV-positive human sera. The nanosensors could differentiate DENV-positive sera from other flavivirus-infected patients, including ZIKV, and were even able to distinguish which DENV serotype infected individual patients. Readouts are obtained in ELISA-plate spectrophotometers without the need of specific devices.


Assuntos
Técnicas Biossensoriais/métodos , Dengue/diagnóstico , Ressonância de Plasmônio de Superfície/métodos , Infecção por Zika virus/diagnóstico , Anticorpos Antivirais/sangue , Brasil , Estudos de Coortes , Dengue/virologia , Ouro/química , Humanos , Nanopartículas Metálicas/química , Estudos Soroepidemiológicos , Proteínas do Envelope Viral/imunologia , Infecção por Zika virus/virologia
8.
J Inorg Biochem ; 206: 111017, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32120160

RESUMO

Cancer-Associated Fibroblasts (CAFs) contribute to tumour progression and have received significant attention as a therapeutic target. These cells produce growth factors, cytokines and chemokines, stimulating cancer cell proliferation and inhibiting their apoptosis. Recent advances in drug delivery have demonstrated a significant promise of iron oxide nanoparticles in clinics as theranostic agents, mainly due to their magnetic properties. Here, we designed superparamagnetic iron oxide nanoparticles (SPIONs) to induce apoptosis of human fibroblasts. SPIONs were synthesized via co-precipitation method and coated with sodium citrate (SPION_Cit). We assessed the intracellular uptake of SPIONs by human fibroblast cells, as well as their cytotoxicity and ability to induce thermal effects under the magnetic field. The efficiency and time of nanoparticle internalization were assessed by Prussian Blue staining, flow cytometry and transmission electron microscopy. SPIONs_Cit were detected in the cytoplasm of human fibroblasts 15 min after in vitro exposure, entering into cells mainly via endocytosis. Analyses through Cell Titer Blue assay, AnnexinV-fluorescein isothiocyanate (FITC) and propidium iodide (PI) cellular staining demonstrated that concentrations below 8 × 10-2 mg/mL of SPIONs_Cit did not alter cell viability of human fibroblast. Furthermore, it was also demonstrated that SPIONs_Cit associated with alternating current magnetic field were able to induce hyperthermia and human fibroblast cell death in vitro, mainly through apoptosis (83.5%), activating caspase 8 (extrinsic apoptotic via) after a short exposure period. Collectively these findings suggest that our nanoplatform is biocompatible and can be used for therapeutic purposes in human biological systems, such as inducing apoptosis of CAFs.


Assuntos
Apoptose/efeitos dos fármacos , Compostos Férricos/farmacologia , Fibroblastos/efeitos dos fármacos , Nanopartículas Magnéticas de Óxido de Ferro/administração & dosagem , Fibroblastos Associados a Câncer/efeitos dos fármacos , Morte Celular/efeitos dos fármacos , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Ácido Cítrico/química , Endocitose , Compostos Férricos/química , Citometria de Fluxo , Humanos , Hipertermia Induzida , Nanopartículas Magnéticas de Óxido de Ferro/química , Microscopia Eletrônica de Transmissão , Neoplasias/metabolismo , Neoplasias/patologia
9.
Arch Environ Contam Toxicol ; 73(4): 649-658, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28687867

RESUMO

Multi-walled carbon nanotubes (MWCNTs) have potential applications in the industrial, agricultural, pharmaceutical, medical, and environmental remediation fields. However, many uncertainties exist regarding the environmental implications of engineered nanomaterials. This study examined the effect of the MWCNTs on metabolic status and morphology of filamentous green microalgae Klebsormidium flaccidum. Appropriate concentrations of MWCNT (1, 50, and 100 µg mL-1) were added to a microalgal culture in the exponential growth phase and incubated for 24, 48, 72, and 96 h. Exposure to MWCNT led to reductions in algal growth after 48 h and decreased on cell viability for all experimental endpoints except for 1 µg mL-1 at 24 h and 100 µg mL-1 after 72 h. At 100 µg mL-1, MWCNTs induced reactive oxygen species (ROS) production and had an effect on intracellular adenosine triphosphate (ATP) content depending on concentration and time. No photosynthetic activity variation was observed. Observations by scanning transmission electron microscopy showed cell damage. In conclusion, we have demonstrated that exposure to MWCNTs affects cell metabolism and microalgal cell morphology. To our best knowledge, this is the first case in which MWCNTs exhibit adverse effects on filamentous green microalgae K. flaccidum. These results contribute to elucidate the mechanism of MWCNT nanotoxicity in the bioindicator organism of terrestrial and freshwater habitats.


Assuntos
Microalgas/fisiologia , Nanotubos de Carbono/toxicidade , Poluentes Químicos da Água/toxicidade , Sobrevivência Celular/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo
10.
Int J Radiat Biol ; 93(9): 958-966, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28609167

RESUMO

PURPOSE: To investigate the effects of high dose rate (HDR) brachytherapy on cellular progression of a radioresistant human squamous cell carcinoma in vitro, based on clinical parameters. MATERIALS AND METHODS: An acrylic platform was designed to attach tissue culture flasks and assure source positioning during irradiation. At exponential phase, A431cells, a human squamous cell carcinoma, were irradiated twice up to 1100 cGy. Cellular proliferation was assessed by Trypan blue exclusion assay and survival fraction was calculated by clonogenic assay. DNA content analysis and cell cycle phases were assessed by flow cytometry and gel electrophoresis, respectively. Cellular death patterns were measured by HOPI double-staining method. RESULTS: Significant decreasing cellular proliferation rate (p < 0.05) as well as reduced survival fraction (p < 0.001) in irradiated cells were observed. Moreover, increased percentage of cells arrested in the G2/M phase (32.3 ± 1.5%) in the irradiated group as compared with untreated cells (8.22 ± 1.2%) was detected. Also, a significant (p < 0.0001) nuclei shrinking in irradiated cells without evidence of necrosis or apoptosis was found. CONCLUSION: HDR brachytherapy led to a decreased proliferation rate and cell survival and also hampered cellular progression to mitosis suggesting that tumor cell death mainly occurred due to mitotic death and G2/M cell cycle arrest.


Assuntos
Apoptose/efeitos da radiação , Braquiterapia/métodos , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/radioterapia , Ciclo Celular/efeitos da radiação , Proliferação de Células/efeitos da radiação , Linhagem Celular Tumoral , Relação Dose-Resposta à Radiação , Humanos , Hipofracionamento da Dose de Radiação , Resultado do Tratamento
11.
J Nanobiotechnology ; 15(1): 26, 2017 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-28376812

RESUMO

BACKGROUND: Dengue is the most prevalent arthropod-borne viral disease in the world. In this article we present results on the development, characterization and immunogenic evaluation of an alternative vaccine candidate against Dengue. METHODS: The MWNT-DENV3E nanoconjugate was developed by covalent functionalization of carboxylated multi-walled carbon nanotubes (MWNT) with recombinant dengue envelope (DENV3E) proteins. The recombinant antigens were bound to the MWNT using a diimide-activated amidation process and the immunogen was characterized by TEM, AFM and Raman Spectroscopy. Furthermore, the immunogenicity of this vaccine candidate was evaluated in a murine model. RESULTS: Immunization with MWNT-DENV3E induced comparable IgG responses in relation to the immunization with non-conjugated proteins; however, the inoculation of the nanoconjugate into mice generated higher titers of neutralizing antibodies. Cell-mediated responses were also evaluated, and higher dengue-specific splenocyte proliferation was observed in cell cultures derived from mice immunized with MWNT-DENV3E when compared to animals immunized with the non-conjugated DENV3E. CONCLUSIONS: Despite the recent licensure of the CYD-TDV dengue vaccine in some countries, results from the vaccine's phase III trial have cast doubts about its overall efficacy and global applicability. While questions about the effectiveness of the CYD-TDV vaccine still lingers, it is wise to keep at hand an array of vaccine candidates, including alternative non-classical approaches like the one presented here.


Assuntos
Formação de Anticorpos , Vacinas contra Dengue/imunologia , Dengue/prevenção & controle , Nanotubos de Carbono/química , Proteínas do Envelope Viral/imunologia , Animais , Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , Antígenos Virais/imunologia , Proliferação de Células , Citocinas/imunologia , Dengue/imunologia , Vacinas contra Dengue/uso terapêutico , Vírus da Dengue/imunologia , Feminino , Imunidade Celular , Imunoglobulina G/sangue , Camundongos , Camundongos Endogâmicos BALB C , Microscopia de Força Atômica , Microscopia Eletrônica de Transmissão , Nanoconjugados/química , Nanomedicina , Proteínas Recombinantes/química , Proteínas Recombinantes/imunologia , Análise Espectral Raman , Baço/citologia , Vacinas de Subunidades Antigênicas/imunologia , Vacinas de Subunidades Antigênicas/uso terapêutico
12.
Medchemcomm ; 8(10): 1993-2002, 2017 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-30108718

RESUMO

In this work, we characterize nor-ß-lapachone-loaded (NßL-loaded) microcapsules prepared using an emulsification/solvent extraction technique. Features such as surface morphology, particle size distribution, zeta potential, optical absorption, Raman and Fourier transform infrared spectra, thermal analysis data, drug encapsulation efficiency, drug release kinetics and in vitro cytotoxicity were studied. Spherical microcapsules with a size of 1.03 ± 0.46 µm were produced with an encapsulation efficiency of approximately 19%. Quantum DFT calculations were also performed to estimate typical interaction energies between a single nor-ß-lapachone molecule and the surface of the microparticles. The NßL-loaded PLGA microcapsules exhibited a pronounced initial burst release. After the in vitro treatment with NßL-loaded microcapsules, a clear phagocytosis of the spheres was observed in a few minutes. The cytotoxic activity against a set of cancer cell lines was investigated.

13.
Sci Rep ; 6: 33588, 2016 09 19.
Artigo em Inglês | MEDLINE | ID: mdl-27642034

RESUMO

The pellucid zone (PZ) is a protective embryonic cells barrier against chemical, physical or biological substances. This put, usual transfection methods are not efficient for mammal oocytes and embryos as they are exclusively for somatic cells. Carbon nanotubes have emerged as a new method for gene delivery, and they can be an alternative for embryos transfection, however its ability to cross the PZ and mediated gene transfer is unknown. Our data confirm that multiwall carbon nanotubes (MWNTs) can cross the PZ and delivery of pDNA into in vitro-fertilized bovine embryos. The degeneration rate and the expression of genes associated to cell viability were not affected in embryos exposed to MWNTs. Those embryos, however, had lower cell number and higher apoptotic cell index, but this did not impair the embryonic development. This study shows the potential utility of the MWNT for the development of new method for delivery of DNA into bovine embryos.


Assuntos
Blastocisto/metabolismo , DNA/administração & dosagem , Técnicas de Transferência de Genes , Nanotubos de Carbono , Animais , Bovinos , Técnicas de Cultura de Células , Células Cultivadas , Feminino , Genes Reporter , Nanotubos de Carbono/química , Nanotubos de Carbono/ultraestrutura , Técnicas de Transferência Nuclear , Plasmídeos/administração & dosagem , Plasmídeos/genética , Gravidez
14.
Molecules ; 21(7)2016 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-27384551

RESUMO

Prostate cancer is one of the most common malignant tumors in males and it has become a major worldwide public health problem. This study characterizes the encapsulation of Nor-ß-lapachone (NßL) in poly(d,l-lactide-co-glycolide) (PLGA) microcapsules and evaluates the cytotoxicity of the resulting drug-loaded system against metastatic prostate cancer cells. The microcapsules presented appropriate morphological features and the presence of drug molecules in the microcapsules was confirmed by different methods. Spherical microcapsules with a size range of 1.03 ± 0.46 µm were produced with an encapsulation efficiency of approximately 19%. Classical molecular dynamics calculations provided an estimate of the typical adsorption energies of NßL on PLGA. Finally, the cytotoxic activity of NßL against PC3M human prostate cancer cells was demonstrated to be significantly enhanced when delivered by PLGA microcapsules in comparison with the free drug.


Assuntos
Benzofuranos/administração & dosagem , Cápsulas , Preparações de Ação Retardada , Portadores de Fármacos , Ácido Láctico , Naftoquinonas/administração & dosagem , Ácido Poliglicólico , Antineoplásicos/administração & dosagem , Antineoplásicos/química , Benzofuranos/química , Cápsulas/química , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sistemas de Liberação de Medicamentos , Humanos , Concentração Inibidora 50 , Ácido Láctico/química , Masculino , Modelos Moleculares , Conformação Molecular , Estrutura Molecular , Naftoquinonas/química , Ácido Poliglicólico/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Neoplasias da Próstata , Análise Espectral Raman
15.
Nanomedicine (Lond) ; 10(15): 2423-50, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26244905

RESUMO

Graphene and its derivatives, due to a wide range of unique properties that they possess, can be used as starting material for the synthesis of useful nanocomplexes for innovative therapeutic strategies and biodiagnostics. Here, we summarize the latest progress in graphene and its derivatives and their potential applications for drug delivery, gene delivery, biosensor and tissue engineering. A simple comparison with carbon nanotubes uses in biomedicine is also presented. We also discuss their in vitro and in vivo toxicity and biocompatibility in three different life kingdoms (bacterial, mammalian and plant cells). All aspects of how graphene is internalized after in vivo administration or in vitro cell exposure were brought about, and explain how blood-brain barrier can be overlapped by graphene nanomaterials.


Assuntos
Grafite/química , Nanoestruturas , Microscopia Eletrônica de Transmissão , Engenharia Tecidual
16.
Cell Commun Signal ; 12: 78, 2014 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-25539979

RESUMO

BACKGROUND: Succinate is an intermediate of the citric acid cycle as well as an extracellular circulating molecule, whose receptor, G protein-coupled receptor-91 (GPR91), was recently identified and characterized in several tissues, including heart. Because some pathological conditions such as ischemia increase succinate blood levels, we investigated the role of this metabolite during a heart ischemic event, using human and rodent models. RESULTS: We found that succinate causes cardiac hypertrophy in a GPR91 dependent manner. GPR91 activation triggers the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2), the expression of calcium/calmodulin dependent protein kinase IIδ (CaMKIIδ) and the translocation of histone deacetylase 5 (HDAC5) into the cytoplasm, which are hypertrophic-signaling events. Furthermore, we found that serum levels of succinate are increased in patients with cardiac hypertrophy associated with acute and chronic ischemic diseases. CONCLUSIONS: These results show for the first time that succinate plays an important role in cardiomyocyte hypertrophy through GPR91 activation, and extend our understanding of how ischemia can induce hypertrophic cardiomyopathy.


Assuntos
Cardiopatias/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Ácido Succínico/metabolismo , Adulto , Animais , Animais Recém-Nascidos , Pressão Sanguínea/efeitos dos fármacos , Cálcio/metabolismo , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo , Cardiopatias/patologia , Histona Desacetilases/metabolismo , Humanos , Cirrose Hepática/metabolismo , Camundongos Knockout , Pessoa de Meia-Idade , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Ratos Wistar , Ácido Succínico/sangue
17.
Microsc Res Tech ; 76(12): 1278-83, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24123490

RESUMO

Combined microscopy techniques are used to establish the usability of phosphonic acid layers as promoters of hydroxyapatite (HAp) growth. Using spread coating, octadecylphosphonic acid (OPA) self-assembled bilayers are delivered to the thin natural oxide layer of a titanium film surface with no prior treatment. These bilayers aggregate two major advantages of phosphonic moieties to titanium surfaces: nucleation of hydroxyapatite crystals from ionic solution and affinity for both titanium oxide surface and HAp crystals. The functionalized substrates and bare titanium (control) samples are immersed in an aqueous solution containing calcium and phosphorus ions. Over a 4-week immersion time, OPA-functionalized substrates present numerous large agglomerates of inorganic crystals, in contrast to control samples, with no significant amount of deposits. Initial sample characterization was performed with atomic force microscopy (AFM). Compositional and structural characterization of these agglomerates (using TEM, EDS, and electron diffraction), revealed that they are indeed HAp, the main component of the inorganic bone matrix.


Assuntos
Matriz Óssea/química , Materiais Revestidos Biocompatíveis/química , Durapatita/química , Cálcio/química , Cristalização , Durapatita/metabolismo , Microscopia de Força Atômica , Microscopia Eletrônica de Transmissão , Microscopia de Varredura por Sonda , Ácidos Fosforosos/química , Fósforo/química , Propriedades de Superfície , Titânio/química
18.
Int J Nanomedicine ; 7: 4511-29, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22923989

RESUMO

In recent years, significant progress has been made in organ transplantation, surgical reconstruction, and the use of artificial prostheses to treat the loss or failure of an organ or bone tissue. In recent years, considerable attention has been given to carbon nanotubes and collagen composite materials and their applications in the field of tissue engineering due to their minimal foreign-body reactions, an intrinsic antibacterial nature, biocompatibility, biodegradability, and the ability to be molded into various geometries and forms such as porous structures, suitable for cell ingrowth, proliferation, and differentiation. Recently, grafted collagen and some other natural and synthetic polymers with carbon nanotubes have been incorporated to increase the mechanical strength of these composites. Carbon nanotube composites are thus emerging as potential materials for artificial bone and bone regeneration in tissue engineering.


Assuntos
Proteínas da Matriz Extracelular/química , Nanotubos de Carbono/química , Engenharia Tecidual/métodos , Alicerces Teciduais , Animais , Proteínas da Matriz Extracelular/metabolismo , Humanos , Células-Tronco/citologia , Células-Tronco/metabolismo
19.
Adv Exp Med Biol ; 740: 891-916, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22453975

RESUMO

The increasing interest in stem cell research is linked to the promise of developing treatments for many lifethreatening, debilitating diseases, and for cell replacement therapies. However, performing these therapeutic innovations with safety will only be possible when an accurate knowledge about the molecular signals that promote the desired cell fate is reached. Among these signals are transient changes in intracellular Ca(2+) concentration [Ca(2+)](i). Acting as an intracellular messenger, Ca(2+) has a key role in cell signaling pathways in various differentiation stages of stem cells. The aim of this chapter is to present a broad overview of various moments in which Ca(2+)-mediated signaling is essential for the maintenance of stem cells and for promoting their development and differentiation, also focusing on their therapeutic potential.


Assuntos
Sinalização do Cálcio/fisiologia , Células-Tronco/citologia , Animais , Cálcio/metabolismo , Diferenciação Celular , Células-Tronco Embrionárias/citologia , Perfilação da Expressão Gênica , Humanos , Células-Tronco Neurais/citologia
20.
Materials (Basel) ; 4(3): 575-584, 2011 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-28880007

RESUMO

Carbon nanotubes (CNTs) and nanofibers (CNFs) were synthesized on clinker and silica fume particles in order to create a low cost cementitious nanostructured material. The synthesis was carried out by an in situ chemical vapor deposition (CVD) process using converter dust, an industrial byproduct, as iron precursor. The use of these materials reduces the cost, with the objective of application in large-scale nanostructured cement production. The resulting products were analyzed by scanning electron microscopy (SEM), transmission electron microscopy (TEM) and thermogravimetric analysis (TGA) and were found to be polydisperse in size and to have defective microstructure. Some enhancement in the mechanical behavior of cement mortars was observed due to the addition of these nano-size materials. The contribution of these CNTs/CNFs to the mechanical strength of mortar specimens is similar to that of high quality CNTs incorporated in mortars by physical mixture.

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