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1.
Int J Nanomedicine ; 14: 5369-5379, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31409993

RESUMO

Purpose: Photothermal therapy (PTT) exploits the light-absorbing properties of nanomaterials such as silica-gold nanoshells (NS) to inflict tumor death through local hyperthermia. However, in in vivo studies of PTT, the heat distribution is often found to be heterogeneous throughout the tumor volume, which leaves parts of the tumor untreated and impairs the overall treatment outcome. As this challenges PTT as a one-dose therapy, this study here investigates if giving the treatment repeatedly, ie, fractionated PTT, increases the efficacy in mice bearing subcutaneous tumors. Methods: The NS heating properties were first optimized in vitro and in vivo. Two fractionated PTT protocols, consisting of two and four laser treatments, respectively, were developed and applied in a murine subcutaneous colorectal tumor model. The efficacy of the two fractionated protocols was evaluated both by longitudinal monitoring of tumor growth and, at an early time point, by positron emission tomography (PET) imaging of 18F-labeled glucose analog 18F-FDG. Results: Overall, there were no significant differences in tumor growth and survival between groups of mice receiving single-dose PTT and fractionated PTT in our study. Nonetheless, some animals did experience inhibited tumor growth or even complete tumor disappearance due to fractionated PTT, and these animals also showed a significant decrease in tumor uptake of 18F-FDG after therapy. Conclusion: This study only found an effect of giving PTT to tumors in fractions compared to a single-dose approach in a few animals. However, many factors can affect the outcome of PTT, and reliable tools for optimization of treatment protocol are needed. Despite the modest treatment effect, our results indicate that 18F-FDG PET/CT imaging can be useful to guide the number of treatment sessions necessary.


Assuntos
Hipertermia Induzida , Fototerapia , Animais , Linhagem Celular Tumoral , Modelos Animais de Doenças , Relação Dose-Resposta à Radiação , Feminino , Glicerol/química , Ouro/química , Temperatura Alta , Raios Infravermelhos , Camundongos Endogâmicos BALB C , Nanoconchas/química , Nanoconchas/ultraestrutura , Neoplasias/patologia , Neoplasias/terapia , Tomografia por Emissão de Pósitrons , Dióxido de Silício/química , Resultado do Tratamento , Carga Tumoral
2.
Phys Chem Chem Phys ; 21(35): 19686-19694, 2019 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-31469369

RESUMO

In this study the glass transition temperatures (Tgα and Tgß) in mesoporous silica-based amorphous drugs were characterized. For this purpose, mesoporous silica Parteck SLC (MPS) was loaded with the drugs ibuprofen and carvedilol, either below, at, or above the monomolecular drug loading capacities, i.e. the concentration at which the entire MPS surface is covered with a monolayer of drug molecules. The resulting amorphous forms were analysed using X-ray powder diffraction and the thermal behaviour was characterised with differential scanning calorimetry (DSC) and dynamic mechanical analysis (DMA). The drug monolayer did not contribute to the thermal signal in DSC. Using DMA however, it could be shown that the monolayer indeed exhibited a very weak Tgα, and that the temperature range of this transition did not differ from that of the quench cooled amorphous drugs. Theoretical ab initio molecular dynamics simulations revealed that the nature of hydrogen bonding geometry of the functional groups interacting with the MPS surface were similar to that of the respective crystalline drugs, which results in restricted molecular motions for those functional groups. On the other hand, the non-interacting parts of the molecules exhibited molecular motions similar to what is observed in pure amorphous drugs. As a result of the interactions of the monolayer with the MPS surface, the monomolecular drug layer did not reveal a Tgß. However, a Tgß was found at any drug-MPS ratios above the monomolecular drug loading capacity as a result of the excess drug which forms a "true" amorphous phase. Overall, this study demonstrated that drug molecules forming an amorphous monolayer on the surfaces of a mesoporous silica particle, even though they are restricted in their mobility, exhibit a Tgα, but lack a Tgß, whereas any excess drug confined in the MPS pores showed similar properties as the pure amorphous drug. These findings will help to increase the overall understanding of drug loaded MS systems, including their physical stability as well as release properties.


Assuntos
Vidro/química , Dióxido de Silício/química , Temperatura de Transição , Varredura Diferencial de Calorimetria , Carvedilol/química , Liberação Controlada de Fármacos , Estabilidade de Medicamentos , Ibuprofeno/química , Simulação de Dinâmica Molecular
3.
Life Sci ; 234: 116756, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31419444

RESUMO

AIMS: Conventional radiotherapy is mainly restricted by the low radiation absorption efficiency of tumors tissues and the hypoxic tumor cells radio-resistance. In this paper, novel nano-radiosensitizers, magnetic nanoparticles core coated with silica, were successfully prepared to overcome these limitations. MAIN METHODS: The prepared nanoparticles have been characterized by transmission electron microscope (TEM), Dynamic light scattering (DLS), atomic force microscope (AFM) and vibration sample magnetometer (VSM). MTT cytotoxicity and DNA double-strand breaks (Comet) assays have been used to assess the radio-enhancing effect of iron oxide magnetic nanoparticles (IO-MNPs) and silica-coated iron oxide magnetic nanoparticles (SIO-MNPs) against MCF7 breast cancer cells. MCF7 cells were treated with different concentrations of the prepared nanoformulations and exposed to an electron beam at doses 0, 0.5, 1, 2, 4 Gy. KEY FINDINGS: DLS measurements revealed that the main hydrodynamic diameter of the prepared IO-MNPs and SIO-MNPs was 18.17 ±â€¯4.5 nm and 164.18 ±â€¯16.1 nm, respectively, which was confirmed by TEM micrographs. MTT and comet assays results showed that the radiosensitizing effect of the prepared nanoformulations was dose and concentration dependent. Interestingly, the dose enhancement factor (DEF) for SIO-MNPs was, on average, 1.3-fold greater than that of IO-MNPs. SIGNIFICANCE: Coating of IO-MNPs with silica led to enhance their electron radiosensitization and consequently their therapeutic efficacy. Therefore, SIO-MNPs represent a promising engineered nano-formulation for enhancing breast cancer radiosensitivity.


Assuntos
Neoplasias da Mama/radioterapia , Compostos Férricos/uso terapêutico , Nanopartículas/uso terapêutico , Radiossensibilizantes/uso terapêutico , Dióxido de Silício/uso terapêutico , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Sobrevivência Celular/efeitos da radiação , Dano ao DNA/efeitos da radiação , Elétrons , Feminino , Compostos Férricos/química , Humanos , Células MCF-7 , Nanopartículas/química , Radiossensibilizantes/química , Dióxido de Silício/química
4.
Chem Biol Interact ; 311: 108774, 2019 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-31369748

RESUMO

Silica nanoparticles (SiNPs) are one of the popular nanomaterials used in industrial manufacturing, synthesis, engineering, and medicine. Recently, mechanisms underlying toxicity of silica nanoparticles have been reported; however, their uptake mechanisms have still not fully understood. In this study, toxicity of SiNPs was investigated in the nematode Caenohabditis elegans by using microarray and pathway analysis focusing the uptake mechanisms and their impact on toxicity. Physicochemical characterization of SiNPs was performed using dynamic light scattering (DLS) and zeta potential. No mortality was observed after 24 h exposure to SiNPs. However, reproductive ability was significantly reduced at the same concentrations. To ascertain a global mechanism of toxicity, microarray was conducted on C. elegans exposed to 10 mg/L SiNPs (20% reduction in reproductive ability). Microarray results indicated that genes involved in reproduction, such as msp (Major Sperm Protein) genes, were significantly downregulated in C. elegans exposed to SiNPs. Pathway analyses on differentially expressed genes (DEGs) revealed that endocytic pathway as a major pathway involved in the uptake of SiNPs. Involvement of endocytic pathway in the uptake of SiNPs was assessed using specific inhibitors (methyl-ß-cyclodextrin, chlorpromazine, and LY294002 for caveolin-, clathrin-, and pinocytosis-mediated endocytosis, respectively). The inhibitor assay indicated that an internalization process facilitated by clathrin-mediated endocytosis is involved in the uptake of SiNPs. Functional analysis using endocytosis defective mutants, (i,e.  cav-1, cup-2, and chc-1) confirmed the role of endocytosis on the reproductive toxicity of SiNPs. Overall results suggest that clathrin-mediated endocytosis pathway is a potential mechanism of uptake of SiNPs in C. elegans that in turn, affects general toxic outcome, such as, decrease in reproductive ability.


Assuntos
Caenorhabditis elegans/metabolismo , Clatrina/metabolismo , Endocitose/efeitos dos fármacos , Nanopartículas/toxicidade , Dióxido de Silício/química , Animais , Caenorhabditis elegans/crescimento & desenvolvimento , Redes Reguladoras de Genes/efeitos dos fármacos , Nanopartículas/química , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Reprodução/efeitos dos fármacos , beta-Ciclodextrinas/química , beta-Ciclodextrinas/farmacologia
5.
Int J Nanomedicine ; 14: 5061-5071, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31371947

RESUMO

Background: Photodynamic therapy (PDT) is widely recognized as a promising way to cure cancer. However, the limited tumor homing property of currently available drug delivery systems (DDSs) is the bottleneck for the delivery of photodynamic agents. Purpose: In our study, we decorated silica nanoparticles (SLN) with cell membrane (CM) derived from SGC7901 cells to construct carrier (CM/SLN) which was able to to specifically target the homogenous SGC7901 cells. Materials and methods: Furthermore, the decent drug loading capability of CM/SLN was adopted to load photodynamic agent chlorins e6 (Ce6) to finally construct aDDS suitable for tumor-targeted PDT of gastric cancer. Results: The experimental results suggested that CM/SLN/Ce6 was nano-sized particles with good dispersion and stability in physiological conditions. Moreover, due to the modification of CM,CM/SLN/Ce6 could specifically target the homogenous SGC7901 cells both in vitro and in vivo. Most importantly, further in vivo results demonstrated that the CM/SLN/Ce6 showed a better anticancer outcome compared to SLN/Ce6. Conclusion: CM/SLN/Ce6 might be a promising platform for effective tumor targeted PDT of gastric cancer.


Assuntos
Membrana Celular/patologia , Nanopartículas/química , Fotoquimioterapia , Porfirinas/uso terapêutico , Dióxido de Silício/química , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/patologia , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Peso Corporal/efeitos dos fármacos , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Membrana Celular/efeitos dos fármacos , Coloides , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Humanos , Camundongos , Nanopartículas/ultraestrutura , Tamanho da Partícula , Porfirinas/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Eletricidade Estática , Distribuição Tecidual/efeitos dos fármacos , Carga Tumoral/efeitos dos fármacos
6.
Pharm Res ; 36(10): 147, 2019 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-31414240

RESUMO

PURPOSE: The aim was to design and thoroughly characterize monodisperse Fe3O4@SiO2-Ag nanoparticles with strong antibacterial properties, which makes them a candidate for targeting bacterial infections. METHODS: The monodisperse Fe3O4 nanoparticles were prepared by oleic acid-stabilized thermal decomposition of Fe(III) oleate; the particles were coated with silica shell using a water-in-oil reverse microemulsion, involving hydrolysis and condensation of tetramethyl orthosilicate. Resulting Fe3O4@SiO2 particles were modified by (3-mercaptopropyl)trimethoxysilane to introduce 1.1 mmol SH/g. Finally, the Fe3O4@SiO2-SH nanoparticles were decorated with silver nanoclusters formed by reduction of silver nitrate with NaBH4. The particles were analyzed by FTIR, X-ray photoelectron and atomic absorption spectroscopy, dynamic light scattering and vibrating sample magnetometry. The antibacterial activity of the Fe3O4@SiO2 and Fe3O4@SiO2-Ag nanoparticles was tested against Gram-positive Staphylococcus aureus and Gram-negative Escherichia coli bacteria cultivated on Luria agar plates or in Luria broth. RESULTS: The superparamagnetic Fe3O4@SiO2-Ag nanoparticles (21 nm in diameter; saturation magnetization 26 A∙m2/kg) were successfully obtained and characterized. Inhibitory and toxic effects against bacteria were documented by incubation of the Fe3O4@SiO2-Ag nanoparticles with Staphylococcus aureus and Escherichia coli. CONCLUSIONS: The combination of magnetic properties together with bactericidal effects is suitable for the disinfection of medical instruments, water purification, food packaging, etc.


Assuntos
Antibacterianos/química , Nanopartículas de Magnetita/química , Prata/química , Antibacterianos/farmacologia , Escherichia coli/efeitos dos fármacos , Ácido Oleico/química , Tamanho da Partícula , Silanos/química , Dióxido de Silício/química , Prata/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Propriedades de Superfície
7.
Phys Chem Chem Phys ; 21(34): 18741-18752, 2019 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-31424464

RESUMO

Medical application of nanotechnology implies the development of nanomaterials capable of being functional in different biological environments. In this sense, elongated nanoparticles (e-MNPs) with high-aspect ratio have demonstrated more effective particle cellular internalization, which is favoured by the increased surface area. This paper makes use of an environmentally friendly hydrothermal method to produce magnetic iron oxide e-MNPs, starting from goethite precursors. At high temperatures (Td) goethite transforms into hematite, which subsequently reduces to magnetite when exposed to a hydrogen atmosphere for a certain time. It is shown that by adjusting Td it is possible to obtain Fe3O4 e-MNPs with partially controlled specific surface area and magnetic properties, attributed to different porosity of the samples. The particles' efficiencies for diagnostic and therapeutic purposes (in magnetic resonance imaging and magnetic fluid hyperthermia, respectively) are very good in terms of clinical standards, some samples showing transversal proton nuclear relaxivity r2 (B0 = 1.33 T) = 340 s-1 mM-1 and specific absorption rate SAR > 370 W g-1 at high field amplitudes (B0 = 55 mT). Direct correlations between the SAR, relaxivity, magnetic properties and porosity of the samples are found, and the physico-chemical processes underneath these correlations are investigated. Our results open the possibility of using very efficient high-aspect ratio elongated nanoparticles with optimized chemico-physical properties for biomedical applications.


Assuntos
Nanopartículas de Magnetita/química , Temperatura Alta , Hidrogênio/química , Magnetismo , Conformação Molecular , Fenômenos Físicos , Dióxido de Silício/química , Propriedades de Superfície
8.
Int J Nanomedicine ; 14: 5503-5526, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31410001

RESUMO

Background and purpose: Glioma is one of the most aggressive primary brain tumors and is incurable. Surgical resection, radiation, and chemotherapies have been the standard treatments for brain tumors, however, they damage healthy tissue. Therefore, there is a need for safe anticancer drug delivery systems. This is particularly true for natural prodrugs such as thymoquinone (TQ), which has a high therapeutic potential for cancers but has poor water solubility and insufficient targeting capacity. We have tailored novel core-shell nanoformulations for TQ delivery against glioma cells using mesoporous silica nanoparticles (MSNs) as a carrier. Methods: The core-shell nanoformulations were prepared with a core of MSNs loaded with TQ (MSNTQ), and the shell consisted of whey protein and gum Arabic (MSNTQ-WA), or chitosan and stearic acid (MSNTQ-CS). Nanoformulations were characterized, studied for release kinetics and evaluated for anticancer activity on brain cancer cells (SW1088 and A172) and cortical neuronal cells-2 (HCN2) as normal cells. Furthermore, they were evaluated for caspase-3, cytochrome c, cell cycle arrest, and apoptosis to understand the possible anticancer mechanism. Results: TQ release was pH-dependent and different for core and core-shell nanoformulations. A high TQ release from MSNTQ was detected at neutral pH 7.4, while a high TQ release from MSNTQ-WA and MSNTQ-CS was obtained at acidic pH 5.5 and 6.8, respectively; thus, TQ release in acidic tumor environment was enhanced. The release kinetics fitted with the Korsmeyer-Peppas kinetic model corresponding to diffusion-controlled release. Comparative in vitro tests with cancer and normal cells indicated a high anticancer efficiency for MSNTQ-WA compared to free TQ, and low cytotoxicity in the case of normal cells. The core-shell nanoformulations significantly improved caspase-3 activation, cytochrome c triggers, cell cycle arrest at G2/M, and apoptosis induction compared to TQ. Conclusion: Use of MSNs loaded with TQ permit improved cancer targeting and opens the door to translating TQ into clinical application. Particularly good results were obtained for MSNTQ-WA.


Assuntos
Antineoplásicos/uso terapêutico , Benzoquinonas/uso terapêutico , Composição de Medicamentos , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Glioma/tratamento farmacológico , Nanopartículas/química , Dióxido de Silício/química , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Benzoquinonas/farmacologia , Materiais Biocompatíveis/química , Encéfalo/patologia , Varredura Diferencial de Calorimetria , Caspase 3/metabolismo , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Quitosana/química , Citocromos c/metabolismo , Difusão , Ativação Enzimática/efeitos dos fármacos , Humanos , Concentração de Íons de Hidrogênio , Concentração Inibidora 50 , Cinética , Nanopartículas/ultraestrutura , Porosidade , Espectroscopia de Infravermelho com Transformada de Fourier , Termogravimetria
9.
Int J Nanomedicine ; 14: 5611-5622, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31413566

RESUMO

Background: Multimodal imaging probes have become a powerful tool for improving detection sensitivity and accuracy, which are important in disease diagnosis and treatment. Methods: In this study, novel bifunctional magnetic resonance imaging (MRI)/fluorescence probes were prepared by loading gadodiamide into fluorescent silica nanoparticles (NPs) (Gd@Cy5.5@SiO2-PEG-Ab NPs) for targeting of prostate cancer (PCa). The physicochemical characteristics, biosafety and PCa cell targeting ability of the Gd@Cy5.5@SiO2-PEG-Ab NPs were studied in vitro and in vivo. Results: The Gd@Cy5.5@SiO2-PEG-Ab NPs had a spherical morphology with a relatively uniform size distribution and demonstrated high efficiency for Gd loading. In vitro and in vivo cell-targeting experiments demonstrated a high potential for the synthesized NPs to target prostate-specific membrane antigen (PSMA) receptor-positive PCa cells, enabling MRI and fluorescence imaging. In vitro cytotoxicity assays and in vivo hematological and pathological assays showed that the prepared NPs exhibited good biological safety. Conclusion: Our study demonstrates that the synthesized Gd@Cy5.5@SiO2-PEG-Ab NPs have great potential as MRI/fluorescence contrast agents for specific identification of PSMA receptor-positive PCa cells.


Assuntos
Gadolínio DTPA/química , Imagem por Ressonância Magnética , Nanopartículas/química , Polietilenoglicóis/química , Neoplasias da Próstata/diagnóstico por imagem , Dióxido de Silício/química , Animais , Anticorpos/metabolismo , Linhagem Celular Tumoral , Meios de Contraste , Endocitose , Fluorescência , Glutamato Carboxipeptidase II/metabolismo , Humanos , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , Nanopartículas/toxicidade , Nanopartículas/ultraestrutura , Especificidade de Órgãos , Polietilenoglicóis/síntese química , Padrões de Referência
10.
Int J Nanomedicine ; 14: 5785-5797, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31440047

RESUMO

Introduction: The targeted delivery of anti-cancer drugs to tumor tissue has been recognized as a promising strategy to increase their therapeutic efficacy and reduce side effects. Mesoporous silica-coated superparamagnetic Fe3O4 nanoparticles (NH2-MSNs), a kind of nanocarrier, can passively enter tumor tissues to enhance the permeability and retention of drugs. However, NH2-MSNs do not specifically bind to cancer cells. This drawback encouraged us to develop a more efficient nanocarrier for cancer therapy. Methods: Herein, we describe the development of an effective nanocarrier based on NH2-MSNs, which were modified with hyaluronic acid on their surface (HA-MSNs) and loaded with doxorubicin (DOX). We have successfully fabricated uniform spherical HA-MSNs nanocarriers. The targeting ability of this delivery system was evaluated through specific uptake by cells and IVIS imaging. Results: DOX-HA-MSNs nanocarriers displayed more dramatic cytotoxic activity against 4T1 breast cancer cells compared to GES-1 gastric mucosa cells. In vivo results revealed that once DOX-HA-MSNs nanocarriers are exposed to an external magnetic field, they could be rapidly attracted to the magnet and effectively cross the cytoplasmic membrane via CD44 receptor-mediated transcytosis. This allows them to access the cancer cell cytoplasm and release DOX based on changes in the physiological environment. Both in vitro and in vivo results demonstrated that the HA-MSNs nanocarriers provided better therapeutic efficacy. Conclusion: The HA-MSNs nanocarriers represent an effective new paradigm to treat cancers due to active targeting to the tumor cells. Moreover, the specific uptake by the tumor effectively protects normal tissues to reduce off-target side effects. The reported findings support further investigation of HA-MSNs for cancer therapy.


Assuntos
Dextranos/química , Sistemas de Liberação de Medicamentos , Ácido Hialurônico/química , Nanopartículas de Magnetita/química , Dióxido de Silício/química , Animais , Linhagem Celular Tumoral , Doxorrubicina/administração & dosagem , Doxorrubicina/farmacologia , Humanos , Nanopartículas de Magnetita/ultraestrutura , Camundongos , Nanopartículas/administração & dosagem , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Espectroscopia Fotoeletrônica , Porosidade , Espectroscopia de Infravermelho com Transformada de Fourier , Ensaios Antitumorais Modelo de Xenoenxerto
11.
Int J Nanomedicine ; 14: 5817-5829, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31440049

RESUMO

Purpose: Acetylcholinesterase (AChE) plays a critical role in the transmission of nerve impulse at the cholinergic synapses. Design and synthesis of AChE inhibitors that increase the cholinergic transmission by blocking the degradation of acetylcholine can serve as a strategy for the treatment of AChE-associated disease. Herein, an operational targeted drug delivery platform based on AChE-responsive system has been presented by combining the unique properties of enzyme-controlled mesoporous silica nanoparticles (MSN) with clinical-used AChE inhibitor. Methods: Functionalized MSNs were synthesized by liquid phase method and characterized by using different analytical methods. The biocompatibility and cytotoxicity of MSNs were determined by hemolysis experiment and MTT assay, respectively. Comparison of AChE activity between drug-loading system and inhibitor was developed with kits and by ELISA method. The efficacy of drug-loaded nanocarriers was investigated in a mouse model. Results: Compared with AChE inhibitor itself, the inhibition efficiency of this drug delivery system was strongly dependent on the concentration of AChE. Only AChE with high concentration could cause the opening of pores in the MSN, leading to the controlled release of AChE inhibitor in disease condition. Critically, the drug delivery system can not only exhibit long duration of drug action on AChE inhibition but also reduce the hepatotoxicity in vivo. Conclusion: In summary, AChE-responsive drug release systems have been far less explored. Our results would shed lights on the design of enzyme controlled-release multifunctional system for enzyme-associated disease treatment.


Assuntos
Acetilcolinesterase/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Inibidores da Colinesterase/farmacologia , Portadores de Fármacos/química , Fígado/patologia , Fosfatase Alcalina/sangue , Animais , Aspartato Aminotransferases/sangue , Calixarenos/química , Sobrevivência Celular , Doença Hepática Induzida por Substâncias e Drogas/patologia , Liberação Controlada de Fármacos , Fluoresceína/química , Hemólise , Fígado/efeitos dos fármacos , Masculino , Camundongos Endogâmicos C57BL , Nanopartículas/química , Nanopartículas/ultraestrutura , Fenóis/química , Porosidade , Ratos , Dióxido de Silício/química , Temperatura Ambiente , Fatores de Tempo
12.
Chem Commun (Camb) ; 55(65): 9649-9652, 2019 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-31339160

RESUMO

Intracellular delivery of bioactive polyphenols is currently evaluated as a protective strategy for cells under pharmaceutical stress. To this end, the 20mer R5 peptide from the marine diatom C. fusiformis was N-terminally modified with a quercetin derivative. This polyphenol-peptide conjugate was used to generate homogeneous silica particles under biomimetic conditions that are efficiently taken up by eukaryotic cells without being cytotoxic. However, not only was accumulation in the cytoplasm of living cells observed via electron and fluorescence microscopy but also translocation into the nucleus. The latter was only seen when the quercetin-peptide conjugate was present within the silica particles and provides a novel targeting option for silica particles to nuclei.


Assuntos
Núcleo Celular/metabolismo , Corantes Fluorescentes/farmacocinética , Fragmentos de Peptídeos/farmacocinética , Quercetina/análogos & derivados , Quercetina/farmacocinética , Dióxido de Silício/farmacocinética , Transporte Ativo do Núcleo Celular , Biomimética , Diatomáceas/química , Corantes Fluorescentes/síntese química , Corantes Fluorescentes/química , Corantes Fluorescentes/toxicidade , Células HT29 , Humanos , Fragmentos de Peptídeos/síntese química , Fragmentos de Peptídeos/química , Fragmentos de Peptídeos/toxicidade , Quercetina/síntese química , Quercetina/toxicidade , Dióxido de Silício/química , Dióxido de Silício/toxicidade
13.
Chem Commun (Camb) ; 55(61): 9039-9042, 2019 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-31292589
14.
J Photochem Photobiol B ; 197: 111534, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31279897

RESUMO

In the search for developing a biomedicine based nanomaterial for therapeutic applications, here we described a new benign development of Photo-triggered Gold nanodots capped mesoporous silica nanoparticles Au@MSNs loaded with capsaicin (Cap) for photothermal therapy of cancer cells. Electron microscopic techniques (SEM and TEM) studies depict the anisotropic shape of Cap-Au@MSNs with mean size ≈110 nm. The successful amine functionalization and covalent interaction of Au nanodots on the mesoporous silica surface were confirmed from the results of FTIR, XPS and UV-vis spectral analyses, which directly indicates the composition of synthesized mesoporous silica surface. Additionally, Dynamic Light Scattering (DLS) revealed that synthesized cap-AuMSNs were stable with highly negatively charged. Cap-AuMSNs exhibited extraordinary in vitro antitumor activity against the tested twp thyroid cancer cell lines (i.e., FTC-133 and B-CPAP). 3-(4, 5-Dimethyl-2-thiazolyl)-2, 5-diphenyl-2H tetrazolium bromide (MTT) assay determined that capsaicin and Cap-AuMSNs conferred strong cytotoxicity against the FTC-133 and B-CPAP cell lines. Further, evaluation of the mechanism showed that anticancer activity was achieved by inducing apoptosis in thyroid cancer cells. In addition, we found that such compounds exhibited promising antimetastatic activity and reduced the invasiveness of cancer cells. Hence, we suggesting that these Cap-Au@MSNs can be used as promising candidates for cancer therapy and deserve further investigation.


Assuntos
Capsaicina/química , Raios Infravermelhos , Nanopartículas/química , Nanoestruturas/química , Dióxido de Silício/química , Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Capsaicina/farmacologia , Capsaicina/uso terapêutico , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Ouro/química , Humanos , Microscopia Confocal , Fotoquimioterapia , Porosidade , Câncer Papilífero da Tireoide/tratamento farmacológico , Câncer Papilífero da Tireoide/patologia
15.
Chem Commun (Camb) ; 55(67): 9927-9930, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31334708

RESUMO

Tyrosine phosphorylation regulates the upstream signaling pathway but accounts for less than 0.1% of total phosphorylation in human cells. Herein, molecularly imprinted mesoporous materials were first synthesized to recognize the phosphorylated tyrosine residue from other phosphorylated residues.


Assuntos
Epitopos , Impressão Molecular , Nanopartículas/química , Compostos Organofosforados/química , Dióxido de Silício/química , Tirosina/metabolismo , Adsorção , Cinética , Fosfopeptídeos/química , Fosforilação , Porosidade , Titânio/química
16.
Chem Commun (Camb) ; 55(62): 9104-9107, 2019 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-31298232

RESUMO

We have developed a photoluminescent membrane for microRNA detection, consisting of chemically modified mesoporous silica nanoparticles (CaF2:Yb/Ho@MSNs) attached, via single stranded DNA probes, to flexible polyurethane fibres coated with graphene oxide (GO). By detecting the release of the luminescent nanoparticles resulting from complementary co-hybridization between target miRNA sequences and the DNA probe, accurate measurements of the miRNA concentration at high sensitivity levels can be obtained. The constructs therefore offer a route to rapid detection and the potential for early cancer diagnosis.


Assuntos
Técnicas Biossensoriais , Grafite/química , MicroRNAs/análise , Nanopartículas/química , Dióxido de Silício/química , Tamanho da Partícula , Porosidade , Propriedades de Superfície
17.
Environ Sci Pollut Res Int ; 26(25): 25802-25813, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31270768

RESUMO

In the present study, a comparative analysis was performed on the extraction of nickel ions (Ni2+) from agricultural wastewater using nanosilica (NS) synthesized from barley (NS-B) and wheat (NS-W) grass waste with a yield of 92.4%. The experimental procedure was conducted on barley and wheat waste to obtain an 85% pure NS that served as the adsorbent for nickel extraction in wastewater. The NS was characterized and studied using X-ray fluorescence (XRF), which demonstrated that NS synthesized from barley contained 94.2% SiO2, while NS synthesized from wheat contained 93.0% SiO2. Scanning electron microscopy (SEM) and atomic force microscopy (AFM) were used to determine the surface morphology of the nanoparticles. The energy-dispersive X-ray (EDX) analysis and Fourier transform infrared (FTIR) analysis were used to determine the elements and functional groups of the synthesized particles, respectively. Lastly, particle size and surface area analyses were performed using the Brunauer-Emmett-Teller (BET) method, which determined that the nanoparticles were 70 and 102 nm for NS-B and NS-W, respectively. The adsorption of nickel ions from agricultural wastewater was studied at various concentrations (10-200 mg/L). The kinetic models indicate that sorption equilibrium time was 65 min and that the reaction followed the pseudo-first-order kinetics model with a regression coefficient (R2) of 0.9289. Corresponding studies indicated that the Freundlich isotherms best describe the sorption reaction with an R2 value of 0.9958, which indicates the multilayer adsorption of nickel on the adsorbent. In their standard and real states, the samples indicated that NS-B and NS-W provided high levels of nickel (Ni2+) removal at 95 and 90%, respectively.


Assuntos
Hordeum/química , Triticum/química , Águas Residuárias/análise , Adsorção , Agricultura , Cinética , Microscopia Eletrônica de Varredura , Nanopartículas , Níquel , Tamanho da Partícula , Dióxido de Silício/química , Espectroscopia de Infravermelho com Transformada de Fourier
18.
Environ Sci Pollut Res Int ; 26(25): 25476-25490, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31264155

RESUMO

The rice husk ash (RHA) was used as an alternative source of silica for the synthesis of the functionalized mesoporous material, which was used in the removal of the PAHs naphthalene (Nap), benzo[b]fluoranthene (B[b]F), benzo[k]fluoranthene (B[k]F), and benzo[a]pyrene (B[a]P) from aqueous media. The PABA-MCM-41 (RHA) was characterized using FTIR, TGA, SAXS, and N2 adsorption-desorption analyses. Removal experiments were performed to determine the initial concentrations, individual adsorption in comparison with the mixture of the PAHs, PABA-MCM-41 (RHA) amount, pH, time, and temperature, and the results obtained were statistically analyzed. The PABA-MCM-41 (RHA) presented the SBET, VT, and DBJH values of 438 m2 g-1, 0.41 cm3 g-1, and 3.59 nm, respectively, and good thermal stability. The qe values found in the kinetic equilibrium for the PAHs mixture followed increasing order: Nap < B[a] P < B[k]F < B[b]F, with removal percentages of 89.08 ± 0.00, 93.85 ± 0.28, 94.54 ± 0.10, and 97.80 ± 0.05%, respectively. Graphical abstract.


Assuntos
Fluorenos/química , Oryza/química , Hidrocarbonetos Policíclicos Aromáticos/química , Dióxido de Silício/química , Adsorção , Cinética , Espalhamento a Baixo Ângulo , Temperatura Ambiente , Água , Difração de Raios X
19.
Anal Chim Acta ; 1078: 189-199, 2019 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-31358219

RESUMO

Silica-based lectin microcolumns were developed and optimized for the separation and analysis of glycoform fractions in alpha1-acid glycoprotein (AGP) based on both the degree of branching and level of fucosylation. Concanavalin A (Con A) and Aleuria Aurantia lectin (AAL) were immobilized onto HPLC-grade silica by reductive amination and packed into 2.1 mm i.d. × 5.0 cm microcolumns. Factors examined for these microcolumns include their protein content, binding capacity, binding strength and band-broadening under isocratic conditions (Con A) or step elution conditions (AAL) and in the presence of various flow rates or temperatures. These factors were examined by using experiments based on frontal analysis, zonal elution, peak profiling and peak decay analysis. Up to 200 µg AGP could be loaded onto a Con A microcolumn and provide linear elution conditions, and 100 µg AGP could be applied to an AAL microcolumn. The final conditions for separating retained and non-retained AGP glycoform fractions on a Con A microcolumn used a flow rate of 50 µL min-1 and a temperature of 50 °C, which gave a separation of these fractions within 20 min or less. The final conditions for an AAL microcolumn included a flow rate of 0.75 mL min-1, a temperature of 50 °C, and the use of 2.0 mM l-fucose as a competing agent for elution, giving a separation of non-retained and retained AGP glycoforms in 6 min or less. The inter-day precisions were ±0.7-4.0% or less for the retention times of the AGP glycoforms and ±2.2-3.0% or less for their peak areas.


Assuntos
Orosomucoide/análise , Isoformas de Proteínas/análise , Agaricales/química , Cromatografia de Afinidade/instrumentação , Cromatografia de Afinidade/métodos , Concanavalina A/química , Humanos , Proteínas Imobilizadas/química , Lectinas/química , Orosomucoide/química , Isoformas de Proteínas/química , Reprodutibilidade dos Testes , Dióxido de Silício/química
20.
Food Chem ; 300: 125180, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31325753

RESUMO

An isonicotinic acid hydrazide (INAH) chemically modified fumed silica, as a novel adsorbent, was designed for the preconcentration and determination of Hg (II) ions in fish samples via the solid phase extraction followed by the hydride generation atomic absorption spectrometry (HG-AAS). In this work, the efficiency of the synthesized adsorbent was investigated to determine its ability for the extraction of the Hg (II) ions from the aqueous solutions. The extraction efficiency was investigated by optimizing of different experimental conditions, such as pH, sample volume, flow rate, adsorbent dosage, and eluent type. Under the optimal conditions, a linear calibration curve for the solid phase extraction method was obtained in the range of between 0.12 and 16.5 µg L-1. The obtained detection limit and preconcentration factor were 0.018 µg L-1 and 25, respectively (RSD > 3%). The proposed optimized method was successfully applied to fish samples.


Assuntos
Produtos Pesqueiros/análise , Mercúrio/análise , Nanopartículas/química , Extração em Fase Sólida/métodos , Espectrofotometria Atômica/métodos , Adsorção , Animais , Contaminação de Alimentos/análise , Concentração de Íons de Hidrogênio , Limite de Detecção , Mercúrio/isolamento & purificação , Dióxido de Silício/química , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/isolamento & purificação
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