Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 372
Filtrar
1.
Ecotoxicol Environ Saf ; 211: 111942, 2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33476850

RESUMO

In this work, the internalization and distribution of citric acid-coated magnetite nanoparticles (here, Fe3O4-NPs) in soybean and alfalfa tissues and their effects on plant growth were studied. Both legumes were germinated in pots containing an inert growing matrix (vermiculite) to which Hoagland solution without (control, C), with Fe3O4-NPs (50 and 100 mgironL-1, NP50 and NP100), or with the same amount of soluble iron supplied as Fe-EDTA (Fe50, Fe100) was added once before sowing. Then, plants were watered with the standard nutrient solution. The observation of superparamagnetic signals in root tissues at harvest (26 days after emergence) indicated Fe3O4-NPs uptake by both legumes. A weak superparamagnetic signal was also present in the stems and leaves of alfalfa plants. These findings suggest that Fe3O4-NPs are readily absorbed but not translocated (soybean) or scarcely translocated (alfalfa) from the roots to the shoots. The addition of both iron sources resulted in increased root weight; however, only the addition of Fe3O4-NPs resulted in significantly higher root surface; shoot weight also increased significantly. As a general trend, chlorophyll content enhanced in plants grown in vermiculite supplemented with extra iron at pre-sowing; the greatest increase was observed with NP50. The only antioxidant enzyme significantly affected by our treatments was catalase, whose activity increased in the roots and shoots of both species exposed to Fe3O4-NPs. However, no symptoms of oxidative stress, such as increased lipid peroxidation or reactive oxygen species accumulation, were evidenced in any of these legumes. Besides, no evidence of cell membrane damage or cell death was found. Our results suggest that citric acid-coated Fe3O4-NPs are not toxic to soybean and alfalfa; instead, they behave as plant growth stimulators.


Assuntos
Ácido Cítrico/química , Nanopartículas de Magnetita/química , Medicago sativa/crescimento & desenvolvimento , Soja/crescimento & desenvolvimento , Clorofila/metabolismo , Ácido Cítrico/metabolismo , Germinação , Ferro/metabolismo , Nanopartículas de Magnetita/toxicidade , Medicago sativa/metabolismo , Nanopartículas/metabolismo , Desenvolvimento Vegetal , Folhas de Planta/metabolismo , Raízes de Plantas/metabolismo , Soja/metabolismo
2.
ACS Appl Mater Interfaces ; 13(1): 287-297, 2021 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-33356111

RESUMO

Malaria is one of the deadliest infectious diseases threatening half of the world population. With the deterioration of the parasiticidal effect of the current antimalarials, novel approaches such as screening of more specific inhibitors and targeted delivery of drugs have been under intensive research. Herein, we prepare hollow mesoporous ferrite nanoparticles (HMFNs) of 200 nm with ferromagnetic properties using a one-pot hydrothermal reaction. A magnetically targeted drug-delivery system coloaded with artemisinin in the inner magnetite shell and heparin on the outer mesoporous shell (HMFN@ART@HEP) is developed. Specific targeting of the magnetic nanoparticles to the parasite-infected erythrocytes is achieved by the attraction between the HMFNs and hemozoin (paramagnetic), a vital metabolite of plasmodium in the erythrocytic stage. With the hemozoin production reaching the maximum during the schizont period of the parasite, HMFN@ART@HEPs are adsorbed to the infected red blood cells (iRBCs), which not only interferes with the release of merozoites but also significantly enhances the inhibitory efficacy due to the increased local concentration of artemisinin. Subsequently, the heparin coated on the surface of the nanoparticles can efficiently interfere with the invasion of freshly released merozoites to new RBCs through the specific interaction between the parasite-derived ligands and heparin, which further increases the inhibitory effect on malaria. As a cluster of heparin, heparin-coated nanoparticles provide stronger blocking capability than free heparin, resulting from multivalent interactions with surface receptors on merozoite. Thus, we have developed a HMFN-based delivery system with considerable antimalarial efficacy, which is a promising platform for treatment against malaria.


Assuntos
Antimaláricos/farmacologia , Artemisininas/farmacologia , Heparina/farmacologia , Nanopartículas de Magnetita/química , Adsorção , Células Hep G2 , Heparina/química , Heparina/toxicidade , Humanos , Nanopartículas de Magnetita/toxicidade , Merozoítos/química , Merozoítos/efeitos dos fármacos , Testes de Sensibilidade Parasitária , Plasmodium falciparum/química , Plasmodium falciparum/efeitos dos fármacos , Porosidade
3.
Int J Nanomedicine ; 15: 3605-3620, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32547017

RESUMO

Purpose: Osteonecrosis of the femoral head (ONFH) is a chronic and irreversible disease that eventually develops into a joint collapse and results in joint dysfunction. Early intervention and treatment are essential for preserving the joints and avoiding hip replacement. In this study, a system of human umbilical mesenchymal stem cells-supermagnetic iron oxide nanoparticles (NPs) @polydopamine (SCIOPs) was constructed. The magnetic targeting system gathers in the lesion area, inhibits the apoptosis of bone cells, enhances osteogenic effect, and effectively treats ONFH under external magnetic field. Materials and Methods: The supermagnetic iron oxide NPs @polydopamine (SPION@PDA NPs) were characterized by transmission electron microscopy and zeta potential, respectively. The effects of SPION@PDA NPs on the viability, proliferation, and differentiation of stem cells were detected by the CCK8 method, flow cytometry, and staining, respectively. The serum inflammatory indicators were detected by Luminex method. The bone mass of the femoral head was analyzed by micro computed tomography. The expression of apoptosis and osteoblast-related cytokines was detected by Western blotting. The osteogenesis of the femoral head was detected by histological and immunohistochemical sections. Results: The SCIOPs decreased the pro-inflammatory factors, and the micro CT showed that the bone repair of the femoral head was enhanced after treatment. The hematoxylin and eosin sections also showed an increase in the osteogenesis in the femoral head. Western blotting results showed and increased expression of anti-apoptotic proteins Akt and Bcl-2, decreased expression of apoptotic proteins caspase-3 and Bad, and increased expression of osteogenic proteins Runx-2 and Osterix in the femoral head. Conclusion: Under the effect of magnetic field and homing ability of stem cells, SCIOPs inhibited the apoptosis of osteoblasts, improved the proliferation ability of osteoblasts, and promoted bone repair in the femoral head through the Akt/Bcl-2/Bad/caspase-3 signaling pathway, thereby optimizing the tissue repair ability.


Assuntos
Necrose da Cabeça do Fêmur/induzido quimicamente , Necrose da Cabeça do Fêmur/terapia , Glucocorticoides/efeitos adversos , Fenômenos Magnéticos , Nanopartículas de Magnetita/química , Células-Tronco Mesenquimais/citologia , Transdução de Sinais , Animais , Apoptose/efeitos dos fármacos , Caspase 3/metabolismo , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Citocinas/metabolismo , Feminino , Hemólise/efeitos dos fármacos , Humanos , Indóis/química , Nanopartículas de Magnetita/toxicidade , Nanopartículas de Magnetita/ultraestrutura , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/metabolismo , Osteogênese/efeitos dos fármacos , Polímeros/química , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Microtomografia por Raio-X , Proteína de Morte Celular Associada a bcl/metabolismo
4.
J Nanobiotechnology ; 18(1): 64, 2020 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-32334582

RESUMO

BACKGROUND: The primary strategy to repair peripheral nerve injuries is to bridge the lesions by promoting axon regeneration. Thus, the ability to direct and manipulate neuronal cell axon regeneration has been one of the top priorities in the field of neuroscience. A recent innovative approach for remotely guiding neuronal regeneration is to incorporate magnetic nanoparticles (MNPs) into cells and transfer the resulting MNP-loaded cells into a magnetically sensitive environment to respond to an external magnetic field. To realize this intention, the synthesis and preparation of ideal MNPs is an important challenge to overcome. RESULTS: In this study, we designed and prepared novel fluorescent-magnetic bifunctional Fe3O4·Rhodamine 6G@polydopamine superparticles (FMSPs) as neural regeneration therapeutics. With the help of their excellent biocompatibility and ability to interact with neural cells, our in-house fabricated FMSPs can be endocytosed into cells, transported along the axons, and then aggregated in the growth cones. As a result, the mechanical forces generated by FMSPs can promote the growth and elongation of axons and stimulate gene expression associated with neuron growth under external magnetic fields. CONCLUSIONS: Our work demonstrates that FMSPs can be used as a novel stimulator to promote noninvasive neural regeneration through cell magnetic actuation.


Assuntos
Axônios/fisiologia , Óxido Ferroso-Férrico/química , Indóis/química , Nanopartículas de Magnetita/química , Polímeros/química , Rodaminas/química , Animais , Axônios/efeitos dos fármacos , Caderinas/genética , Caderinas/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Exocitose , Regulação da Expressão Gênica/efeitos dos fármacos , Indóis/farmacologia , Nanopartículas de Magnetita/toxicidade , Camundongos , Microscopia Confocal , Microscopia Eletrônica de Transmissão , Regeneração Nervosa/efeitos dos fármacos , Ácido Oleico/química , Células PC12 , Polímeros/farmacologia , Proteína Fosfatase 1/genética , Proteína Fosfatase 1/metabolismo , Ratos
5.
Langmuir ; 36(16): 4405-4415, 2020 04 28.
Artigo em Inglês | MEDLINE | ID: mdl-32243164

RESUMO

This paper presents sols of uncoated and citric acid-coated Fe3O4 nanoparticles obtained by a combination of coprecipitation and sonochemistry methods. A stable concentrated CA-Fe3O4 sol synthesized by a combination of coprecipitation with an inconvenient Fe2+/Fe3+ ratio, modification with citric acid and US treatment was obtained for the first time. A comparative analysis of the composition and morphology of nanoparticles was performed. The sols are oppositely charged and behave as a typical ferrofluid. The citric acid-modified sol is aggregatively stable over wider ranges of pH and electrolyte concentration, but it becomes less stable with the temperature increase. DLVO calculations showed that steric repulsion forces are a vital factor contributing to increased aggregative stability in a modified Fe3O4 sol. The experiments have revealed the magneto-optical effect in a modified Fe3O4 sol with an electrolyte concentration of 0.025-0.075 M caused by a high potential barrier and a deep secondary minimum in pairwise interaction curves. The "pK spectroscopy" mathematical model to describe the potentiometric curves of synthesized magnetite sols was used for the first time. According to potentiometric titration, the ions of the electrolyte practically do not contribute to formation of a surface charge in modified Fe3O4 with a change in pH due to blocking the magnetite surface by citric acid molecules. Drosophila melanogaster was used as a model to show that Fe3O4 in chronic exposure has a low toxic effect.


Assuntos
Drosophila melanogaster/efeitos dos fármacos , Longevidade/efeitos dos fármacos , Nanopartículas de Magnetita/química , Soluções/química , Animais , Ácido Cítrico/química , Ácido Cítrico/toxicidade , Feminino , Fenômenos Magnéticos , Nanopartículas de Magnetita/toxicidade , Masculino , Fenômenos Ópticos , Tamanho da Partícula , Soluções/toxicidade
6.
Nanotoxicology ; 14(4): 504-532, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32037933

RESUMO

Engineered Nanomaterials (NMs), such as Superparamagnetic Iron Oxide Nanoparticles (SPIONs), offer significant benefits in a wide range of applications, including cancer diagnostic and therapeutic strategies. However, the use of NMs in biomedicine raises safety concerns due to lack of knowledge on possible biological interactions and effects. The initial basis for using SPIONs as biomedical MRI contrast enhancement agents was the idea that they are selectively taken up by macrophage cells, and not by the surrounding cancer cells. To investigate this claim, we analyzed the uptake of SPIONs into well-established cancer cell models and benchmarked this against a common macrophage cell model. In combination with fluorescent labeling of compartments and siRNA silencing of various proteins involved in common endocytic pathways, the mechanisms of internalization of SPIONs in these cell types has been ascertained utilizing reflectance confocal microscopy. Caveolar mediated endocytosis and macropinocytosis are both implicated in SPION uptake into cancer cells, whereas in macrophage cells, a clathrin-dependant route appears to predominate. Colocalization studies confirmed the eventual fate of SPIONs as accumulation in the degradative lysosomes. Dissolution of the SPIONs within the lysosomal environment has also been determined, allowing a fuller understanding of the cellular interactions, uptake, trafficking and effects of SPIONs within a variety of cancer cells and macrophages. Overall, the behavior of SPIONS in non-phagocytotic cell lines is broadly similar to that in the specialist macrophage cells, although some differences in the uptake patterns are apparent.


Assuntos
Meios de Contraste/metabolismo , Endocitose , Macrófagos/metabolismo , Imagem por Ressonância Magnética , Nanopartículas de Magnetita/química , Animais , Transporte Biológico , Linhagem Celular Tumoral , Meios de Contraste/química , Meios de Contraste/toxicidade , Humanos , Processamento de Imagem Assistida por Computador , Lisossomos/metabolismo , Macrófagos/efeitos dos fármacos , Nanopartículas de Magnetita/toxicidade , Microscopia Confocal , Microscopia Eletrônica de Varredura , Tamanho da Partícula , Propriedades de Superfície , Proteínas rab de Ligação ao GTP/metabolismo
7.
Artif Cells Nanomed Biotechnol ; 48(1): 443-451, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32024389

RESUMO

Superparamagnetic iron oxide nanoparticles (SPIONs) have been employed in several biomedical applications where they facilitate both diagnostic and therapeutic aims. Although the potential benefits of SPIONs with different surface chemistry and conjugated targeting ligands/proteins are considerable, complicated interactions between these nanoparticles (NPs) and cells leading to toxic impacts could limit their clinical applications. Hence, elevation of our knowledge regarding the SPION-related toxicity is necessary. Here, the present review article will consider current studies and compare the potential toxic effect of SPIONs with or without identical surface chemistries on different cell lines. It centers on cellular and molecular mechanisms underlying toxicity of SPIONs. Likewise, emphasis is being dedicated for toxicity of SPIONs in various cell lines, in vitro and animal models, in vivo.


Assuntos
Compostos Férricos/farmacocinética , Compostos Férricos/toxicidade , Nanopartículas de Magnetita/toxicidade , Animais , Linhagem Celular , Sobrevivência Celular , Materiais Revestidos Biocompatíveis/toxicidade , Compostos Férricos/química , Humanos , Nanopartículas de Magnetita/química , Nanomedicina , Espécies Reativas de Oxigênio/química , Espécies Reativas de Oxigênio/toxicidade , Distribuição Tecidual
8.
J Nanobiotechnology ; 18(1): 14, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31941495

RESUMO

BACKGROUND: In orthopedics, the treatment of implant-associated infections represents a high challenge. Especially, potent antibacterial effects at implant surfaces can only be achieved by the use of high doses of antibiotics, and still often fail. Drug-loaded magnetic nanoparticles are very promising for local selective therapy, enabling lower systemic antibiotic doses and reducing adverse side effects. The idea of the following study was the local accumulation of such nanoparticles by an externally applied magnetic field combined with a magnetizable implant. The examination of the biodistribution of the nanoparticles, their effective accumulation at the implant and possible adverse side effects were the focus. In a BALB/c mouse model (n = 50) ferritic steel 1.4521 and Ti90Al6V4 (control) implants were inserted subcutaneously at the hindlimbs. Afterwards, magnetic nanoporous silica nanoparticles (MNPSNPs), modified with rhodamine B isothiocyanate and polyethylene glycol-silane (PEG), were administered intravenously. Directly/1/7/21/42 day(s) after subsequent application of a magnetic field gradient produced by an electromagnet, the nanoparticle biodistribution was evaluated by smear samples, histology and multiphoton microscopy of organs. Additionally, a pathohistological examination was performed. Accumulation on and around implants was evaluated by droplet samples and histology. RESULTS: Clinical and histological examinations showed no MNPSNP-associated changes in mice at all investigated time points. Although PEGylated, MNPSNPs were mainly trapped in lung, liver, and spleen. Over time, they showed two distributional patterns: early significant drops in blood, lung, and kidney and slow decreases in liver and spleen. The accumulation of MNPSNPs on the magnetizable implant and in its area was very low with no significant differences towards the control. CONCLUSION: Despite massive nanoparticle capture by the mononuclear phagocyte system, no significant pathomorphological alterations were found in affected organs. This shows good biocompatibility of MNPSNPs after intravenous administration. The organ uptake led to insufficient availability of MNPSNPs in the implant region. For that reason, among others, the nanoparticles did not achieve targeted accumulation in the desired way, manifesting future research need. However, with different conditions and dimensions in humans and further modifications of the nanoparticles, this principle should enable reaching magnetizable implant surfaces at any time in any body region for a therapeutic reason.


Assuntos
Portadores de Fármacos/química , Compostos Férricos/química , Nanopartículas de Magnetita/química , Próteses e Implantes , Dióxido de Silício/química , Animais , Portadores de Fármacos/administração & dosagem , Portadores de Fármacos/farmacocinética , Portadores de Fármacos/toxicidade , Feminino , Corantes Fluorescentes/química , Membro Posterior , Nanopartículas de Magnetita/toxicidade , Camundongos Endogâmicos BALB C , Ortopedia , Polietilenoglicóis/química , Porosidade , Rodaminas/química , Silanos/química , Distribuição Tecidual
9.
Cancer Invest ; 38(1): 61-84, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31791151

RESUMO

Cancer treatment by magnetic hyperthermia offers numerous advantages, but for practical applications many variables still need to be adjusted before developing a controlled and reproducible cancer treatment that is bio-compatible (non-damaging) to healthy cells. In this work, Fe3O4 and CoFe2O4 were synthesized and systematically studied for the development of efficient therapeutic agents for applications in hyperthermia. The biocompatibility of the materials was further evaluated using HepG2 cells as biological model. Colorimetric and microscopic techniques were used to evaluate the interaction of magnetic nano-materials (MNMs) and HepG2 cells. Finally, the behavior of MNMs was evaluated under the influence of an alternating magnetic field (AMF), observing a more efficient temperature increment for CoFe2O4, a desirable behavior for biomedical applications since lower doses and shorter expositions to alternating magnetic field might be required.


Assuntos
Hipertermia Induzida/métodos , Nanopartículas de Magnetita/administração & dosagem , Nanomedicina/métodos , Neoplasias/terapia , Animais , Materiais Biocompatíveis/administração & dosagem , Materiais Biocompatíveis/química , Materiais Biocompatíveis/toxicidade , Cobalto/administração & dosagem , Cobalto/química , Cobalto/toxicidade , Colorimetria , Terapia Combinada/efeitos adversos , Terapia Combinada/métodos , Compostos Férricos/administração & dosagem , Compostos Férricos/química , Compostos Férricos/toxicidade , Óxido Ferroso-Férrico/administração & dosagem , Óxido Ferroso-Férrico/química , Óxido Ferroso-Férrico/toxicidade , Células Hep G2 , Humanos , Hipertermia Induzida/efeitos adversos , Fígado/efeitos da radiação , Terapia de Campo Magnético/efeitos adversos , Terapia de Campo Magnético/métodos , Nanopartículas de Magnetita/química , Nanopartículas de Magnetita/toxicidade , Masculino , Teste de Materiais/métodos , Ratos , Fatores de Tempo , Testes de Toxicidade/métodos
10.
Nanotoxicology ; 14(2): 162-180, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31703536

RESUMO

Mitochondria-associated endoplasmic reticulum (ER) membranes (MAMs) are central microdomains of the ER that interact with mitochondria. MAMs provide an essential platform for crosstalk between the ER and mitochondria and play a critical role in the local transfer of calcium (Ca2+) to maintain cellular functions. Despite the potential uses of superparamagnetic iron oxide nanoparticles (SPIO-NPs) in biomedical applications, the hepatotoxicity of these nanoparticles (NPs) is not well characterized and little is known about the involvement of MAMs in ER-mitochondria crosstalk. We studied SPIO-NPs-associated hepatotoxicity in vitro and in vivo. In vitro, human normal hepatic L02 cells were exposed to SPIO-NPs (2.5, 7.5, and 12.5 µg/mL) for 6 h and SPIO-NPs (12.5 µg/mL) was found to induce apoptosis. In vivo, SPIO-NPs induced liver injury when mice were intravenously injected with 20 mg/kg body weight SPIO-NPs for 24 h. Based on both in vitro and in vivo studies, we found that the structure and Ca2+ transport function of MAMs were perturbated and an accumulation of cyclooxygenase-2 (COX-2) in MAMs fractions was increased upon treatment of SPIO-NPs. The interaction between COX-2 and the components of MAMs, in terms of IP3R-GRP75-VDAC1 complex, was also revealed. Furthermore, the role of COX-2 in SPIO-NPs-associated hepatotoxicity was investigated by modifying the expression of COX-2. We demonstrated that COX-2 increases the structural and functional ER-mitochondria coupling and enhances the efficacy of ER-mitochondria Ca2+ transfer through the MAMs, thus sensitizing hepatocytes to a mitochondrial Ca2+ overload-dependent apoptosis. Taken together, our findings link SPIO-NPs-triggered hepatotoxicity with ER-mitochondria Ca2+ crosstalk which is mediated by COX-2 and provide mechanistic insight into the impact of interorganelle ER-mitochondria communication on hepatic nanotoxicity.


Assuntos
Ciclo-Oxigenase 2/metabolismo , Retículo Endoplasmático/efeitos dos fármacos , Hepatócitos/efeitos dos fármacos , Nanopartículas de Magnetita/toxicidade , Mitocôndrias Hepáticas/efeitos dos fármacos , Membranas Mitocondriais/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Cálcio/metabolismo , Técnicas de Cultura de Células , Doença Hepática Induzida por Substâncias e Drogas/enzimologia , Doença Hepática Induzida por Substâncias e Drogas/patologia , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Ciclo-Oxigenase 2/genética , Inibidores de Ciclo-Oxigenase 2/uso terapêutico , Retículo Endoplasmático/enzimologia , Retículo Endoplasmático/metabolismo , Proteínas de Choque Térmico HSP70/metabolismo , Hepatócitos/enzimologia , Hepatócitos/metabolismo , Humanos , Proteínas de Membrana/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Mitocôndrias Hepáticas/enzimologia , Mitocôndrias Hepáticas/metabolismo , Membranas Mitocondriais/enzimologia , Canal de Ânion 1 Dependente de Voltagem/metabolismo
11.
Food Chem Toxicol ; 136: 110989, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31760074

RESUMO

Superparamagnetic iron oxide nanoparticles (SPION) require stable surface modifications to render safe nanocapsules for biomedical applications. Herein, two types of surface modified poly(lactic-co-glycolic acid)-encapsulated SPION were synthesized using either α-tocopheryl-polyetheleneglycol-succinate (TPGS) or didodecyl-dimethyl-ammonium-bromide (DMAB) as surfactants by emulsification. SPION-TPGS (180 nm) was larger than SPION-DMAB (25 nm) and uncoated SPION (10 nm). Both formulations were positively charged and induced lower cyto-genotoxicity and ROS generation than uncoated SPION in human lymphocytes. SPION-DMAB was least cyto-genotoxic among the three. Based on these results, mice were gavaged with the formulations for 5 consecutive days and biocompatibility studies were performed on the 7th and 21st days. ICP-AES and Prussian blue staining revealed the internalization of SPION-DMAB in brain and spleen, and SPION-TPGS in liver and kidney on day 7. This was correlated with high DNA damage and oxidative stress in the same organs. Substantial clearance of Fe was accompanied by reduced genotoxicity and oxidative stress on day 21. Therefore, SPION-DMAB can be further studied for oral drug delivery to the brain and imaging of cerebral tissue without any functional ligand or external magnetic field.


Assuntos
Materiais Biocompatíveis/toxicidade , Dano ao DNA/efeitos dos fármacos , Nanopartículas de Magnetita/toxicidade , Mutagênicos/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Animais , Materiais Biocompatíveis/química , Humanos , Ferro/metabolismo , Linfócitos/efeitos dos fármacos , Nanopartículas de Magnetita/química , Masculino , Camundongos , Testes de Mutagenicidade , Mutagênicos/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Compostos de Amônio Quaternário/química , Cabeça do Espermatozoide/efeitos dos fármacos , Propriedades de Superfície , Vitamina E/química
12.
Chemosphere ; 238: 124562, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31442774

RESUMO

Superparamagnetic iron oxide nanoparticles (SPION) have been widely studied for different biomedical and environmental applications. In this study we evaluated the toxicity and potential alterations of relevant physiological parameters caused to the microalga Chlamydomonas reinhardtii (C. reinhardtii) upon exposure to SPION. The results showed dose-dependent toxicity. A mechanistic study combining flow cytometry and physiological endpoints showed a toxic response consisting of a decrease in metabolic activity, increased oxidative stress and alterations in the mitochondrial membrane potential. Additionally, and due to the light absorption of SPION suspensions, we observed a significant shading effect, causing a marked decrease in photosynthetic activity. In this work, we demonstrated for the first time, the internalization of SPION by endocytosis in C. reinhardtii. These results demonstrated that SPION pose a potential risk for the environment if not managed properly.


Assuntos
Chlamydomonas reinhardtii/efeitos dos fármacos , Nanopartículas de Magnetita/toxicidade , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Microalgas/efeitos dos fármacos , Fotossíntese/efeitos dos fármacos , Endocitose/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo
13.
Toxicol Mech Methods ; 30(1): 48-59, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31364912

RESUMO

This work was aimed at defining the suitable test for evaluating Fe3O4 NPs cytotoxicity after short-term exposure in human mesenchymal stem cells (hMSCs) using different viability tests, namely NRU, MTT and TB assays, paralleled by cell morphology analyses for cross checking. MTT and NRU data (culture medium with/without hMSCs plus Fe3O4NPs) indicated artificial/false increments in cell viability after Fe3O4NPs. These observations did not fit with the morphological analyses showing reduced cell density, loss of monolayer features, and morphological alterations at Fe3O4NPs ≥50 µg/ml. Fe3O4NPs alone induced a substantial increased absorbance at the wavelength required for MTT and NRU. A significant death (25%) of hMSC at Fe3O4NPs ≥10 µg/ml, with a maximum effect (45%) at 300 µg/ml after 24 h, exacerbated after 48 h, was observed when applying TB test. These results paralleled the effects on cell morphology. The optical properties and stability of Fe3O4NP suspension (tendency to agglomerate in a specific culture medium) represent factors that limit in vitro result interpretation. These findings suggest the non applicability of the spectrophotometric assays for hMSC culture conditions, while TB is an accurate method for determining cell viability after Fe3O4NP exposure in this model. In relation to NPs safety assessment: cell-based assays must be considered on case-by-case basis; selection of relevant cell models is also important for predictive toxicological studies; application of a testing strategy is fundamental for understanding the toxicity pathways driving cellular responses.


Assuntos
Bioensaio , Nanopartículas de Magnetita/toxicidade , Células-Tronco Mesenquimais/efeitos dos fármacos , Testes de Toxicidade Aguda , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Relação Dose-Resposta a Droga , Humanos , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/patologia , Medição de Risco , Fatores de Tempo
14.
Neurochem Res ; 45(1): 159-170, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30945145

RESUMO

Superparamagnetic iron oxide nanoparticles (SPIOn) are widely used as a contrast agent for cell labeling. Macrophages are the first line of defense of organisms in contact with nanoparticles after their administration. In this study we investigated the effect of silica-coated nanoparticles (γ-Fe2O3-SiO2) with or without modification by an ascorbic acid (γ-Fe2O3-SiO2-ASA), which is meant to act as an antioxidative agent on rat peritoneal macrophages. Both types of nanoparticles were phagocytosed by macrophages in large amounts as confirmed by transmission electron microscopy and Prusian blue staining, however they did not substantially affect the viability of exposed cells in monitored intervals. We further explored cytotoxic effects related to oxidative stress, which is frequently documented in cells exposed to nanoparticles. Our analysis of double strand breaks (DSBs) marker γH2AX showed an increased number of DSBs in cells treated with nanoparticles. Nanoparticle exposure further revealed only slight changes in the expression of genes involved in oxidative stress response. Lipid peroxidation, another marker of oxidative stress, was not significantly affirmed after nanoparticle exposure. Our data indicate that the effect of both types of nanoparticles on cell viability, or biomolecules such as DNA or lipids, was similar; however the presence of ascorbic acid, either bound to the nanoparticles or added to the cultivation medium, worsened the negative effect of nanoparticles in various tests performed. The attachment of ascorbic acid on the surface of nanoparticles did not have a protective effect against induced cytotoxicity, as expected.


Assuntos
Ácido Ascórbico/metabolismo , Ácido Ascórbico/toxicidade , Macrófagos Peritoneais/efeitos dos fármacos , Macrófagos Peritoneais/metabolismo , Nanopartículas de Magnetita/toxicidade , Animais , Antioxidantes/metabolismo , Antioxidantes/toxicidade , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Células Cultivadas , Relação Dose-Resposta a Droga , Sinergismo Farmacológico , Feminino , Ratos , Ratos Wistar
15.
Mater Sci Eng C Mater Biol Appl ; 107: 110271, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31761218

RESUMO

In this paper we report about the preparation, physicochemical and biological characterization of a magneto responsive nanostructured material based on magnetite nanoparticles (NP) coated with hyaluronic acid (HA). A synthetic approach, based on a Cu(I)-catalyzed azide-alkyne 1,3-dipolar cycloaddition "click" reaction between azido-functionalized magnetite NP and a derivative of hyaluronic acid bearing propargylated ferulic acid groups (HA-FA-Pg), was developed to link covalently the polymer layer to the magnetite NP. The functionalization steps of the magnetite NP and their coating with the HA-FA-Pg layer were monitored by Fourier Transform Infrared (FTIR) spectroscopy and Thermal Gravimetric Analysis (TGA) while Dynamic Light Scattering (DLS) and ζ-potential measurements were performed to characterize the aqueous dispersions of the HA-coated magnetite NP. Aggregation and sedimentation processes were investigated also by UV-visible spectroscopy and the dispersions of HA-coated magnetite NP were found significantly more stable than those of bare NP. Magnetization and zero field cooled/field cooled curves revealed that both bare and HA-coated magnetite NP are superparamagnetic at room temperature. Moreover, cytotoxicity studies showed that the coating with HA-FA-Pg significantly reduces the cytotoxicity of the magnetite NP providing the rational basis for the application of the HA-coated magnetite NP as healthcare material.


Assuntos
Ácido Hialurônico/química , Nanopartículas de Magnetita/química , Animais , Sobrevivência Celular/efeitos dos fármacos , Química Click , Coloides/química , Ácidos Cumáricos/química , Nanopartículas de Magnetita/toxicidade , Camundongos , Células NIH 3T3 , Polímeros/química
16.
Mater Sci Eng C Mater Biol Appl ; 107: 110262, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31761230

RESUMO

Magnetic resonance imaging (MRI) is the most powerful technique for non-invasive diagnosis of human diseases and disorders. Properly designed contrast agents can be accumulated in the damaged zone and be internalized by cells, becoming interesting cellular MRI probes for disease tracking and monitoring. However, this approach is sometimes limited by the relaxation rates of contrast agents currently in clinical use, which show neither optimal pharmacokinetic parameters nor toxicity. In this work, a suitable contrast agent candidate, based on iron oxide nanoparticles (IONPs) coated with polyethyleneglycol, was finely designed, prepared and fully characterized under a physical, chemical and biological point of view. To stand out the real potential of our study, all the experiments were performed in comparison with Ferumoxytol, a FDA approved IONPs. IONPs with a core size of 15 nm and coated with polyethyleneglycol of 5 kDa (OD15-P5) resulted the best ones, being able to be uptaken by both tumoral cells and macrophages and showing no toxicity for in vitro and in vivo experiments. In vitro and in vivo MRI results for OD15-P5 showed r2 relaxivity values higher than Ferumoxitol. Furthermore, the injected OD15-P5 were completely retained at the tumor site for up to 24 h showing high potential as MRI contrast agents for real time long-lasting monitoring of the tumor evolution.


Assuntos
Meios de Contraste/química , Compostos Férricos/química , Imagem por Ressonância Magnética/métodos , Nanopartículas de Magnetita/química , Polietilenoglicóis/química , Animais , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Feminino , Humanos , Nanopartículas de Magnetita/toxicidade , Masculino , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Neoplasias/diagnóstico por imagem , Tamanho da Partícula , Siloxanas/química
17.
J Photochem Photobiol B ; 202: 111716, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31821944

RESUMO

Though anesthetic drug delivery system and drug vehicles is generally applied for pain relief, there are have many difficulties and issues due to its short duration carrier and low biocompatibility, effectiveness at the conditions of inflammation at acidic pH. To resolve this issue, we have designed and developed the dual (pH and temperature) responsive bio-nanomaterial to improve the efficiency anesthetic drug delivery system. Chitosan is a unique class of biomaterials that is widely used in medical devices. The surface engineering of ZnFe2O4 nanoparticles was performed by coating with chitosan using simple precipitation method. Then, multi-active anesthetic drug (Lidocaine) was loaded into nano-ferrite to form a drug delivery vehicle. The prepared drug-vesicle was characterized by using XRD, FTIR, SEM, XPS and TGA analysis. XRD analysis proved the face center cubic structure of zinc nanoferrite. The sustained delivery of Lidocaine (LDC) from CS coated nanoferrite (CS/ZnFe2O4) was stimulated by pH and temperature responsive characteristics of vesicles. The in vitro cytotoxicity of the CS/ZnFe2O4 particles towards fibroblast cells was analyzed by using MTT assay. The drug loaded CS/ZnFe2O4 particles exhibit high biocompatibility and sustained drug release in the physiological pH environment (4.8, 5.5 and 7.4) and temperature responsive (25 and 37 °C) of normal tissues and also drug loading efficiency was measured.


Assuntos
Anestésicos/química , Quitosana/química , Portadores de Fármacos/química , Nanoestruturas/química , Anestésicos/metabolismo , Anestésicos/uso terapêutico , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Liberação Controlada de Fármacos , Humanos , Concentração de Íons de Hidrogênio , Lidocaína/química , Lidocaína/metabolismo , Magnetismo , Nanopartículas de Magnetita/química , Nanopartículas de Magnetita/toxicidade , Nanoestruturas/toxicidade , Dor/tratamento farmacológico , Ratos , Temperatura
18.
Biomater Sci ; 8(1): 201-211, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31664285

RESUMO

Fe3O4 magnetic nanoparticles (MNPs), as one of the most intensively researched NPs, have a range of applications in cancer treatments. In current research, we have focused on the influences of MNPs on cancer cells. We chose polyethyleneimine (PEI) coated MNPs (PEI-MNPs) as a model and they are colloidally stable in biological media. It can be proved that PEI-MNPs result in autophagy induction via mTOR-Akt-p70S6 K and ATG7 signaling pathways. For the first time, we have reported that PEI-MNPs activate both NF-κB and TGF-ß signaling, two key pro-inflammatory pathways, in cancer cells. More significantly, we have found that autophagy induction and NF-κB and TGF-ß activation can be efficiently suppressed through the inhibition of PEI-MNP dependent reactive oxygen species (ROS) over-production. ROS are deemed as a 'double edge sword' for cancer cells, owing to the cancer-suppressing and cancer-promoting actions. Our findings would be useful for designing MNPs induced ROS anti-cancer strategies or diminishing long-term toxic effects.


Assuntos
Autofagia , Óxido Ferroso-Férrico/química , Nanopartículas de Magnetita/química , Polietilenoimina/química , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais , Autofagia/efeitos dos fármacos , Feminino , Células HeLa , Humanos , Nanopartículas de Magnetita/toxicidade , Microscopia de Fluorescência , NF-kappa B/metabolismo , Tamanho da Partícula , Transdução de Sinais/efeitos dos fármacos , Proteína Smad2/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Neoplasias do Colo do Útero/patologia
19.
J Nanobiotechnology ; 17(1): 124, 2019 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-31870377

RESUMO

BACKGROUND: Understanding the in vivo size-dependent pharmacokinetics and toxicity of nanoparticles is crucial to determine their successful development. Systematic studies on the size-dependent biological effects of nanoparticles not only help to unravel unknown toxicological mechanism but also contribute to the possible biological applications of nanomaterial. METHODS: In this study, the biodistribution and the size-dependent biological effects of Fe3O4@SiO2-NH2 nanoparticles (Fe@Si-NPs) in three diameters (10, 20 and 40 nm) were investigated by ICP-AES, serum biochemistry analysis and NMR-based metabolomic analysis after intravenous administration in a rat model. RESULTS: Our findings indicated that biodistribution and biological activities of Fe@Si-NPs demonstrated the obvious size-dependent and tissue-specific effects. Spleen and liver are the target tissues of Fe@Si-NPs, and 20 nm of Fe@Si-NPs showed a possible longer blood circulation time. Quantitative biochemical analysis showed that the alterations of lactate dehydrogenase (LDH) and uric acid (UA) were correlated to some extent with the sizes of Fe@Si-NPs. The untargeted metabolomic analyses of tissue metabolomes (kidney, liver, lung, and spleen) indicated that different sizes of Fe@Si-NPs were involved in the different biochemical mechanisms. LDH, formate, uric acid, and GSH related metabolites were suggested as sensitive indicators for the size-dependent toxic effects of Fe@Si-NPs. The findings from serum biochemical analysis and metabolomic analysis corroborate each other. Thus we proposed a toxicity hypothesis that size-dependent NAD depletion may occur in vivo in response to nanoparticle exposure. To our knowledge, this is the first report that links size-dependent biological effects of nanoparticles with in vivo NAD depletion in rats. CONCLUSION: The integrated metabolomic approach is an effective tool to understand physiological responses to the size-specific properties of nanoparticles. Our results can provide a direction for the future biological applications of Fe@Si-NPs.


Assuntos
Nanopartículas de Magnetita/química , Nanopartículas de Magnetita/toxicidade , Dióxido de Silício/química , Administração Intravenosa , Animais , Rim/metabolismo , L-Lactato Desidrogenase/metabolismo , Fígado/metabolismo , Pulmão/metabolismo , Masculino , Metaboloma , Metabolômica , Tamanho da Partícula , Ratos , Ratos Sprague-Dawley , Baço/metabolismo , Distribuição Tecidual , Ácido Úrico/metabolismo
20.
Int J Nanomedicine ; 14: 8235-8249, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31802864

RESUMO

Background: The effective induction of an antigen-specific T cell immune response through dendritic cell activation is one of the key goals of tumor immunotherapy. Methods: In this study, efficient antigen-delivery carriers using silica-coated magnetic nanoparticles were designed and, their antigen-specific T cell immune response through dendritic cell activation investigated. Results: The results showed that the silica-coated magnetic nanoparticles with conjugated ovalbumin enhanced the production of cytokines and antigen uptake in bone marrow-derived dendritic cells. Also, this induced an antigen-specific cytotoxic T lymphocyte (CTL) immune response and activated antigen-specific Th1 cell responses, including IL-2 and IFN-γ production and proliferation. We proved that the immune-stimulatory effects of silica-coated magnetic nanoparticles with conjugated ovalbumin were efficient in inhibiting of tumor growth in EG7-OVA (mouse lymphoma-expressing ovalbumin tumor-bearing mice model). Conclusion: Therefore, the silica-coated magnetic nanoparticles with conjugated ovalbumin are expected to be useful as efficient anti-cancer immunotherapy agents.


Assuntos
Imunoterapia , Nanopartículas de Magnetita/química , Neoplasias/imunologia , Neoplasias/terapia , Ovalbumina/química , Dióxido de Silício/química , Animais , Antígenos/administração & dosagem , Galinhas , Citocinas/biossíntese , Células Dendríticas/efeitos dos fármacos , Células Dendríticas/imunologia , Feminino , Imunidade , Nanopartículas de Magnetita/toxicidade , Camundongos Endogâmicos C57BL
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...