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1.
Nat Commun ; 11(1): 4249, 2020 08 25.
Artigo em Inglês | MEDLINE | ID: mdl-32843618

RESUMO

Aberrant cell cycle machinery and loss of the CDKN2A tumor suppressor locus make CDK4/6 a potential target in pancreatic ductal adenocarcinoma (PDAC). However, a vast majority of PDAC cases do not harbor a durable response to monotherapy of CDK4/6 inhibitor. Utilizing remote loading to co-encapsulate CDK4/6 inhibitor palbociclib (PAL) and an autophagy inhibitor hydroxychloroquine (HCQ), we demonstrate a ratiometrically designed mesoporous silica nanoformulation with synergistic efficacy in subcutaneous and orthotopic PDAC mouse models. The synergism is attributed to the effective intratumoral buildup of PAL/HCQ, which otherwise exhibit distinctly different circulatory and biodistribution profile. PAL/HCQ co-delivery nanoparticles lead to the most effective shrinkage of PDAC compared to various controls, including free drug mixture. Immunohistochemistry reveals that PAL/HCQ co-delivery nanoparticles trigger anti-apoptotic pathway after repetitive intravenous administrations in mice. When combined with a Bcl inhibitor, the performance of co-delivery nanoparticles is further improved, leading to a long-lasting anti-PDAC effect in vivo.


Assuntos
Autofagia/efeitos dos fármacos , Carcinoma Ductal Pancreático/tratamento farmacológico , Quinase 4 Dependente de Ciclina/antagonistas & inibidores , Quinase 6 Dependente de Ciclina/antagonistas & inibidores , Sistemas de Liberação de Medicamentos , Neoplasias Pancreáticas/tratamento farmacológico , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Modelos Animais de Doenças , Sinergismo Farmacológico , Humanos , Hidroxicloroquina/administração & dosagem , Hidroxicloroquina/química , Hidroxicloroquina/farmacologia , Camundongos , Nanopartículas/administração & dosagem , Nanopartículas/química , Piperazinas/administração & dosagem , Piperazinas/química , Piperazinas/farmacologia , Piridinas/administração & dosagem , Piridinas/química , Piridinas/farmacologia , Dióxido de Silício/administração & dosagem , Dióxido de Silício/química , Dióxido de Silício/farmacologia , Resultado do Tratamento
2.
PLoS One ; 15(7): e0236441, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32701973

RESUMO

Biofilms are microbial communities embedded in an extracellular polymeric matrix and display an enhanced tolerance to the action of antimicrobials. The emergence of novel functionalised nanoparticles is considered a promising avenue for the development of biofilm-specific antimicrobial technologies. However, there is a gap in the understanding of interactions between nanoparticles and the biofilm matrix. Particularly, questions are raised on how nanoparticle charge and surface groups play a role in aggregation when in contact with biofilm components. Herein we present the synthesis of four types of silica nanoparticles and undertake an analysis of their interactions with Pseudomonas fluorescens biofilm matrix. The effect of the biofilm matrix components on the charge and aggregation of the nanoparticles was assessed. Additionally, the study focused on the role of matrix proteins, with the in-depth characterisation of the protein corona of each nanoparticle by Liquid Chromatography with Tandem Mass Spectrometry experiments. The protein corona composition is dependent on the nanoparticle type; non-functionalised nanoparticles show less protein selectivity, whereas carboxylate-functionalised nanoparticles prefer proteins with a higher isoelectric point. These outcomes provide insights into the field of biofilm-nanoparticle interactions that can be valuable for the design of new nano-based targeting systems in future anti-biofilm applications.


Assuntos
Biofilmes/efeitos dos fármacos , Nanopartículas Metálicas/química , Pseudomonas fluorescens/efeitos dos fármacos , Dióxido de Silício/farmacologia , Biofilmes/crescimento & desenvolvimento , Cromatografia Líquida , Humanos , Coroa de Proteína/química , Mapas de Interação de Proteínas/efeitos dos fármacos , Pseudomonas fluorescens/crescimento & desenvolvimento , Dióxido de Silício/química , Espectrometria de Massas em Tandem
3.
Nat Biomed Eng ; 4(8): 835-844, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32541917

RESUMO

In vivo molecular imaging can measure the average kinetics and movement routes of injected cells through the body. However, owing to non-specific accumulation of the contrast agent and its efflux from the cells, most of these imaging methods inaccurately estimate the distribution of the cells. Here, we show that single human breast cancer cells loaded with mesoporous silica nanoparticles concentrating the 68Ga radioisotope and injected into immunodeficient mice can be tracked in real time from the pattern of annihilation photons detected using positron emission tomography, with respect to anatomical landmarks derived from X-ray computed tomography. The cells travelled at an average velocity of 50 mm s-1 and arrested in the lungs 2-3 s after tail-vein injection into the mice, which is consistent with the blood-flow rate. Single-cell tracking could be used to determine the kinetics of cell trafficking and arrest during the earliest phase of the metastatic cascade, the trafficking of immune cells during cancer immunotherapy and the distribution of cells after transplantation.


Assuntos
Rastreamento de Células/métodos , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Meios de Contraste/química , Meios de Contraste/farmacologia , Feminino , Radioisótopos de Gálio/química , Radioisótopos de Gálio/farmacologia , Humanos , Nanopartículas Metálicas/química , Nanopartículas Metálicas/toxicidade , Camundongos , Camundongos Nus , Tomografia por Emissão de Pósitrons , Dióxido de Silício/química , Dióxido de Silício/farmacologia , Imagem Corporal Total
5.
J Nanobiotechnology ; 18(1): 55, 2020 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-32228604

RESUMO

BACKGROUND: Psoriasis is a malignant skin disease characterized as keratinocyte hyperproliferation and aberrant differentiation. Our previous work reported that a bibenzyl compound, erianin, has a potent inhibitory effect on keratinocyte proliferation. To improve its poor water-solubility, increase anti- proliferation activity, and enhance the skin delivery, erianin loaded dendritic mesoporous silica nanospheres (E/DMSNs) were employed. RESULTS: In this work, DMSNs with pore size of 3.5 nm (DMSN1) and 4.6 nm (DMSN2) were fabricated and E/DMSNs showed pore-size-dependent, significantly stronger anti-proliferative and pro-apoptotic effect than free erianin on human immortalized keratinocyte (HaCaT) cells, resulting from higher cellular uptake efficiency. In addition, compared to free erianin, treatment with E/DMSNs was more effective in reducing mitochondrial membrane potential and increasing cytoplasmic calcium levels, which were accompanied by regulation of mitochondria and endoplasmic reticulum stress (ERS) pathway. Porcine skin was utilized in the ex vivo accumulation and permeation studies, and the results indicated higher drug retention and less drug penetration in the skin when administered as the E/DMSNs-loaded hydrogel compared to the erianin-loaded hydrogel. Conlusions This work not only illustrated the further mechanisms of erianin in anti-proliferation of HaCaT cells but also offer a strategy to enhance the efficiency of erianin and the capacity of skin delivery through the DMSNs drug delivery systems.


Assuntos
Apoptose/efeitos dos fármacos , Bibenzilas/farmacologia , Nanosferas/química , Fenol/farmacologia , Dióxido de Silício/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular , Portadores de Fármacos/farmacologia , Sistemas de Liberação de Medicamentos , Humanos , Queratinócitos/efeitos dos fármacos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Pele/efeitos dos fármacos , Neoplasias Cutâneas/tratamento farmacológico , Solubilidade
6.
Tissue Cell ; 63: 101325, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32223954

RESUMO

Healing of critical sized bone defects represents a challenging issue in clinical and research fields. Current therapeutic techniques, such as bone grafts or bone grafts substitutes, still have limitations and drawbacks. Therefore, stem cell-based therapy provides a prospective approach to enhance bone regeneration. The present study aimed to assess the regenerative capacity of Gingival mesenchymal stem cells (GMSCs) as well as Bone marrow mesenchymal stem cells (BMSCs) loaded on NanoBone scaffold, in comparison to the unloaded one, in surgically created bone defects in rabbits' tibiae. To achieve this aim, critical sized bone defects, of 6-mm diameter each, were unilaterally created in tibiae of adult New Zeeland male white rabbits (n = 27). The rabbits were then divided randomly into three groups (9 each) and received the following: Group I: Unloaded NanoBone Scaffold, Group II: GMSCs Loaded on NanoBone Scaffold, and Group III: BMSCs Loaded on NanoBone Scaffold. Three rabbits from each group were then sacrificed at each time point (2, 4 and 6 weeks postoperatively), tibiae were dissected out to evaluate bone healing in the created bony defects; both histologically and histomorphometrically. The findings of this study indicate that both GMSCs and BMSCs exhibited fibroblast morphology and expressed phenotypic MSCs markers. Histologically, local application of GMSCs and BMSCs loaded on NanoBone scaffold showed enhanced the pattern of bone regeneration as compared to the unloaded scaffold. Histomorphometrically, there was astatistically insignificant difference in the new bone area % between the bony defects treated with GMSCs and BMSCs. Thus, GMSCs can be considered as a comparable alternative source to BMSCs in bone regeneration.


Assuntos
Doenças Ósseas/terapia , Regeneração Óssea/genética , Gengiva/citologia , Transplante de Células-Tronco Mesenquimais , Animais , Doenças Ósseas/patologia , Diferenciação Celular/genética , Combinação de Medicamentos , Durapatita/farmacologia , Humanos , Células-Tronco Mesenquimais/citologia , Osteogênese/efeitos dos fármacos , Coelhos , Dióxido de Silício/farmacologia , Engenharia Tecidual/métodos
7.
Artigo em Chinês | MEDLINE | ID: mdl-32306669

RESUMO

Objective: To investigate the role of endoplasmic reticulum stress (ERS) in the autophagy of RAW264.7 cells induced by SiO(2) and its effect on the secretion of tumor necrosis factor-α. Methods: RAW264.7 cells stimulated by 200 µg/ml SiO(2) were used as an vitro cell model, and different treatment times of SiO(2) were used as variables. They were divided into 0 h treatment group (blank control group) , 6 h, 12 h, 24 h, and 48 h treatment group. The formation of autophagospores was detected by acridine orange and mondane-sulfonate (MDC) staining. Application of real-time quantitative PCR (Real-time PCR) to detect autophagy related molecular Beclin1 mRNA expression and protein immunoblot (Western Blotting) detecting autophagy related proteins LC3Ⅰ, LC3Ⅱ and expression of Beclin1. Real-time PCR and Western blotting were used to detect the expression of ERS specific marker BiP. Secretion of RAW 264.7 cell transforming growth factor-ß1 (TGF-ß1) and tumor necrosis factor-α (TNF-α) was detected by enzyme-linked immunosorbent assay (ELISA) . ERS inhibitors 4-PBA intervention experiment, including blank control group, SiO(2), 1 µmol/L 4-PBA+SiO(2), 10 µmol/L 4-PBA+SiO(2), 20 µmol/L 4-PBA+SiO(2) treatment group, Western blotting testing LC3Ⅰ, LC3Ⅱ and expression of Beclin1 changes. Results: Compared with the control group, SiO(2)-induced fluorescence intensity in RAW264.7 cells was significantly increased, with statistically significant differences (P<0.05) . Compared with control group, with SiO(2) processing time prolonged, LC3Ⅰ, LC3Ⅱ Beclin1 mRNA and protein expression and protein expression increased, 6 h, 24 h, the height of the differences were statistically significant (P<0.05) ; Compared with the control group, the mRNA and protein expression level of BiP reached the peak for 6 h, and the expression level in 6 h, 12 h and 24 h groups increased significantly, and the difference was statistically significant (P<0.05) . Compared with the SiO(2) stimulation group, the LC3Ⅱand Beclin 1 protein levels of RAW264.7 cells were gradually down-regulated by increasing the dose of 4-PBA. With the increase of 4-PBA concentration, the down-regulated levels were more significant, and the difference was statistically significant (P<0.05) . Compared with the SiO(2) stimulation group, the TNF-α secretion level of RAW264.7 cells significantly decreased of 1, 10, 20 µmol/L 4-PBA+SiO(2) treatment group, and the difference was statistically significant (P<0.05) . Conclusion: ERS induced by SiO(2) is involved in the secretion of autophagy and TNF-α in RAW264.7 cells.


Assuntos
Autofagia , Estresse do Retículo Endoplasmático , Dióxido de Silício/farmacologia , Fator de Necrose Tumoral alfa/metabolismo , Animais , Camundongos , Células RAW 264.7
8.
An Acad Bras Cienc ; 92(1): e20181120, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32321020

RESUMO

the focus ofthis study was to testthe hypothesisthatthere would be no difference betweenthe biocompatibility of silicon dioxide nanofilms used as antimicrobial agents. Sixty male Wistar rats were divided into 4 groups (n=15): Group C (Control,Polyethylene), Group AR (Acrylic Resin), Group NP (Acrylic Resin coated with NP-Liquid), Group BG (Acrylic Resin coated with Bacterlon).the animals were sacrificed with 7,15 and 30 days and tissues analyzed as regardsthe events of inflammatory infiltrate, edema, necrosis, granulation tissue, mutinucleated giant cells, fibroblasts and collagen. Kruskal-Wallis and Dunn tests was used (P<0.05). Intense inflammatory infiltrate was shown mainly in Groups BG and AR, with significant difference from Control Group inthe time interval of 7days (P=0.004). Necrosis demonstrated significant difference between Group BG and Control Group (P<0.05) inthe time intervals of 7 days. For collagen fibers,there was significant difference betweenthe Control Group and Groups AR and BG inthe time interval of 7 days (P=0.006), and between BG and Control Groups inthe time intervals of 15 days (P=0.010).the hypothesis was rejected. Bacterlon demonstratedthe lowest level, and NP-Liquid Glassthe highest level of tissue compatibility, and best cell repair.the coating with NP-Liquid Glass was demonstrated to be highly promising for clinical use.


Assuntos
Resinas Acrílicas/farmacologia , Materiais Biocompatíveis/farmacologia , Edema/induzido quimicamente , Necrose/induzido quimicamente , Dióxido de Silício/farmacologia , Tela Subcutânea/patologia , Resinas Acrílicas/química , Animais , Materiais Biocompatíveis/química , Edema/patologia , Masculino , Teste de Materiais , Modelos Animais , Necrose/patologia , Ratos , Ratos Wistar , Dióxido de Silício/química , Tela Subcutânea/efeitos dos fármacos
9.
Int J Nanomedicine ; 15: 2287-2302, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32280221

RESUMO

Background: Mitochondrial dysfunction played a vital role in the pathogenesis of various diseases, including acute lung injury (ALI). However, few strategies targeting mitochondria were developed in treating ALI. Recently, we fabricated a porous Se@SiO2 nanoparticles (NPs) with antioxidant properties. Methods: The protective effect of Se@SiO2 NPs was assessed using confocal imaging, immunoblotting, RNA-seq, mitochondrial respiratory chain (MRC) activity assay, and transmission electron microscopy (TEM) in airway epithelial cell line (Beas-2B). The in vivo efficacy of Se@SiO2 NPs was evaluated in a lipopolysaccharide (LPS)-induced ALI mouse model. Results: This study demonstrated that Se@SiO2 NPs significantly increased the resistance of airway epithelial cells under oxidative injury and shifted lipopolysaccharide-induced gene expression profile closer to the untreated controls. The cytoprotection of Se@SiO2 was found to be achieved by maintaining mitochondrial function, activity, and dynamics. In an animal model of ALI, pretreated with the NPs improved mitochondrial dysfunction, thus reducing inflammatory responses and diffuse damage in lung tissues. Additionally, RNA-seq analysis provided evidence for the broad modulatory activity of our Se@SiO2 NPs in various metabolic disorders and inflammatory diseases. Conclusion: This study brought new insights into mitochondria-targeting bioactive NPs, with application potential in curing ALI or other human mitochondria-related disorders.


Assuntos
Lesão Pulmonar Aguda/tratamento farmacológico , Mitocôndrias/efeitos dos fármacos , Nanopartículas/química , Selênio/farmacologia , Dióxido de Silício/farmacologia , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/patologia , Animais , Antioxidantes/química , Antioxidantes/farmacologia , Linhagem Celular , Citoproteção , Modelos Animais de Doenças , Células Epiteliais/metabolismo , Humanos , Lipopolissacarídeos/toxicidade , Pulmão/efeitos dos fármacos , Pulmão/patologia , Camundongos , Mitocôndrias/metabolismo , Nanopartículas/uso terapêutico , Oxirredução , Estresse Oxidativo/efeitos dos fármacos , Porosidade , Selênio/química , Dióxido de Silício/química
10.
Chemosphere ; 254: 126738, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32339799

RESUMO

Biofiltration is a typical air pollution control process for the treatment of volatile organic compounds (VOCs). Mass transfer of hydrophobic VOCs to the biofilm is limited which leads to low removal efficiency (RE). Aiming to enhance the transport of hydrophobic VOCs, the effect of hydrophobic fumed silica (HFS) addition to a biofilter (BF) for pentane removal was studied in this paper. The effect of HFS on pentane removal was evaluated by daily RE measurements and periodical headspace gas pentane pulse injections using SIFT-MS as analysis apparatus. The BF was operated during more than 100 days at an empty bed residence time (EBRT) of 120 s reaching an elimination capacity (EC) up to 93.8 g pentane m-3 h-1. At the last stage of the study, when a higher nutrient pulse and HFS to a concentration of 1.5% w/w wet were added, the BF showed better EC (46.3 ± 14.9 g pentane m-3 h-1; RE = 96.2%) compared to the previous stages (28.3 ± 4.4 g pentane m-3 h-1; RE = 68.3%). This overall performance improvement was in line with the short peak perturbation experiments carried out during the operational time which demonstrated, by net retention time (NRT) determination, to be a fast and reliable tool to gain insights into the behaviour of pollutants inside the BF and its state. Pentane demonstrated to have larger interactions with the packing material when HFS was added. NRT/EBRT ratio variated along the whole operational time, being larger at the last stage.


Assuntos
Poluentes Atmosféricos/isolamento & purificação , Filtração/métodos , Pentanos/isolamento & purificação , Dióxido de Silício/farmacologia , Compostos Orgânicos Voláteis/isolamento & purificação , Poluentes Atmosféricos/análise , Biodegradação Ambiental , Biofilmes , Filtração/instrumentação , Interações Hidrofóbicas e Hidrofílicas , Compostos Orgânicos Voláteis/análise
11.
Lab Invest ; 100(7): 959-973, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32218530

RESUMO

The epithelial-mesenchymal transition (EMT) process is a key priming activity of fibroblasts in pulmonary fibrosis during silicosis. Ets-like protein-1 (Elk-1) is a critical modulator that promotes functional changes in cells, and the effects are mediated by oxidative stress (OS). However, whether ELK-1 is involved in EMT of silicosis remains unclear. In addition, researchers have found that Elk-1 is involved in the expression of the gene zc3h12a, which encodes the protein MCPIP1, and MCPIP1 is a member of the zinc finger Cys-Cys-Cys-His (CCCH)-type protein family. A previous study from our lab showed that ZC3H4, which is also a member of the CCCH-type protein family, critically affected the regulation of EMT during silicosis. However, it has not yet been elucidated if ELK-1 acts at the promoter for zc3h4 to increase its expression in a mechanism that is similar to that of the zc3h12a gene and whether such regulation ultimately controls EMT. Therefore, we explored the correlation between ELK-1 and ZC3H4 expression and tested the underlying mechanisms affecting ELK-1 activation induced by silica. Our study identifies that SiO2-mediated EMT via ELK-1, with the upstream activity of OS and the downstream signaling of ZC3H4 expression resulting in enhanced EMT. These findings suggest that the nuclear transcription factor ELK-1 may be useful as a novel target for the treatment of pulmonary fibrosis.


Assuntos
Proteínas de Ligação a DNA/metabolismo , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Dióxido de Silício/farmacologia , Proteínas Elk-1 do Domínio ets/metabolismo , Animais , Linhagem Celular , Proteínas de Ligação a DNA/genética , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Estresse Oxidativo/efeitos dos fármacos , Proteínas Elk-1 do Domínio ets/genética
12.
Colloids Surf B Biointerfaces ; 188: 110824, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32023511

RESUMO

Despite the clinical approval of few nanomedicines for cancer therapy, some drawbacks still impede their improved efficiency including low drug loading, off-target toxicity and development of multi-drug resistance. Herein, lactoferrin (Lf)-coupled mesoporous silica nanoparticles (MSNPs) were developed for combined delivery of the cytotoxic drug pemetrexed (PMT) and the phytomedicine ellagic acid (EA) for synergistic breast cancer therapy. While the hydrophobic EA was physically encapsulated within the pores of MSNPs via the adsorptive properties of MSNPs and the electrostatic interactions between the negatively charged EA and positively charged amino modified MSNs, the highly water soluble PMT was chemically anchored to the Lf shell through chemical conjugation to the surface of lactoferrin coated MSNPs by carbodiimide reaction to avoid pre-mature drug release and systemic toxicity. The dual drug-loaded Lf-MSNPs (284 nm) demonstrated a sequential faster release of EA followed by a sustained release of PMT. The dual drug-loaded Lf-MSNPs exhibited highest cytotoxicity against MCF-7 (Michigan Cancer Foundation-7) breast cancer cells as revealed by the lowest combination index (CI = 0.885) compared to free drugs. The combination index value (< 1) revealed synergy between both loaded drugs. Furthermore, high cellular uptake of the nanocarriers into MCF-7 breast cancer cells was observed via Lf-receptor mediated endocytosis. Altogether, the dual drug-loaded Lf-targeted MSNPs showed to be a promising carrier for breast cancer therapy through triggering different signaling pathways, and hence overcoming the multi-drug resistance and minimizing the systemic toxicity.


Assuntos
Antineoplásicos/farmacologia , Neoplasias da Mama/tratamento farmacológico , Ácido Elágico/farmacologia , Lactoferrina/farmacologia , Nanopartículas/química , Pemetrexede/farmacologia , Dióxido de Silício/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Neoplasias da Mama/patologia , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Ácido Elágico/química , Humanos , Lactoferrina/química , Células MCF-7 , Estrutura Molecular , Tamanho da Partícula , Pemetrexede/química , Porosidade , Dióxido de Silício/química , Relação Estrutura-Atividade , Propriedades de Superfície , Células Tumorais Cultivadas
13.
ACS Appl Mater Interfaces ; 12(8): 9062-9069, 2020 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-32019301

RESUMO

With increasing ozone depletion, ultraviolet (UV) exposure from sunlight has become a significant health risk. Although commercially available sun protectants provide reasonable protection, they have limitations in terms of safety and aesthetics. Here, we have developed biocompatible and biodegradable sunscreens by facile synthesis of organosilica nanoparticles (o-SNPs) with self-encapsulated phenyl motifs using phenylsilane precursors. The physical structure of o-SNPs is elaborately controlled such that they are large enough to reflect UVA but small enough to be imperceptible when applied on the skin. The chemically attached phenyl motifs to o-SNPs facilitate filtering UVB via their delocalized π-orbitals. The o-SNPs generate a negligible amount of reactive oxygen species under UV exposure. Ex vivo two-photon microscopy reveals that the o-SNPs tend to adhere to the outer layers of skin without further intradermal penetration, resulting in less skin irritation. In vivo UV protection tests confirmed the excellent sunscreen effect of o-SNPs compared with conventional organic and inorganic UV filters.


Assuntos
Materiais Biocompatíveis , Nanopartículas , Dióxido de Silício , Pele , Protetores Solares , Raios Ultravioleta/efeitos adversos , Animais , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Camundongos , Células NIH 3T3 , Nanopartículas/química , Nanopartículas/uso terapêutico , Silanos/química , Dióxido de Silício/química , Dióxido de Silício/farmacologia , Pele/metabolismo , Pele/patologia , Protetores Solares/química , Protetores Solares/farmacologia , Suínos
14.
Molecules ; 25(3)2020 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-32033018

RESUMO

A facile sol-gel route has been applied to synthesize hybrid silica-PVA-iron oxide nanocomposite materials. A step-by-step calcination (processing temperatures up to 400 °C) was applied in order to oxidize the organics together with the iron precursor. Transmission electron microscopy, X-ray diffraction, small angle neutron scattering, and nitrogen porosimetry were used to determine the temperature-induced morpho-textural modifications. In vitro cytotoxicity assay was conducted by monitoring the cell viability by the means of MTT assay to qualify the materials as MRI contrast agents or as drug carriers. Two cell lines were considered: the HaCaT (human keratinocyte cell line) and the A375 tumour cell line of human melanoma. Five concentrations of 10 µg/mL, 30 µg/mL, 50 µg/mL, 100 µg/mL, and 200 µg/mL were tested, while using DMSO (dimethylsulfoxid) and PBS (phosphate saline buffer) as solvents. The HaCaT and A375 cell lines were exposed to the prepared agent suspensions for 24 h. In the case of DMSO (dimethyl sulfoxide) suspensions, the effect on human keratinocytes migration and proliferation were also evaluated. The results indicate that only the concentrations of 100 µg/mL and 200 µg/mL of the nanocomposite in DMSO induced a slight decrease in the HaCaT cell viability. The PBS based in vitro assay showed that the nanocomposite did not present toxicity on the HaCaT cells, even at high doses (200 µg/mL agent).


Assuntos
Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Compostos Férricos/farmacologia , Nanocompostos/química , Álcool de Polivinil/farmacologia , Dióxido de Silício/farmacologia , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Compostos Férricos/química , Humanos , Nanopartículas de Magnetita , Álcool de Polivinil/análogos & derivados , Dióxido de Silício/química , Toxicologia/métodos
15.
Ecotoxicol Environ Saf ; 192: 110253, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32059163

RESUMO

Silica particles can cause a systemic disease in workers termed lung silicosis, characterized by diffuse fibrosis. The development of lung silicosis involves various signaling pathway networks comprising numerous cell types and cytokines. As an important medium for communication between cells, exosomes have emerged as a hot research topic; however, the role of exosomal microRNAs (miRNAs) in silicosis remains unclear. In this study, we conducted high-throughput sequencing to generate exosomal miRNAs profiles from macrophages that were either exposed to silica or not. A total of 298 miRNAs were differentially expressed, with 155 up-regulated and 143 down-regulated. Highly conserved differentially expressed miRNAs were functionally annotated and analyzed to predict target genes. Among target interactions associated with the TGF-ß signaling pathway, miR-125a-5p and its putative target gene, Smurf1, were subjected to further research. As expected, levels of miR-125a-5p were upregulated in human serous exosomes and vitro, and inhibit the exosomal miR-125a-5p suppressed the expression of the fibrosis hallmarks. Besides, high levels of the miRNA led to upregulation of smooth muscle actin alpha and repression of Smurf1 in NIH-3T3 and MRC-5 cells. ID1 and SMAD1, downstream of TGF-ß signaling, were upregulated, indicating potential activation of this signaling pathway. These results contribute to understanding of the intercellular communication mediated by exosomal miRNAs and its critical role in fibroblast to myofibroblast transition and silicosis.


Assuntos
Transdiferenciação Celular/efeitos dos fármacos , Poluentes Ambientais/farmacologia , Exossomos/genética , Fibroblastos/metabolismo , Macrófagos/efeitos dos fármacos , MicroRNAs/metabolismo , Dióxido de Silício/farmacologia , Animais , Perfilação da Expressão Gênica , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Macrófagos/metabolismo , Camundongos , Células NIH 3T3 , Análise de Sequência de RNA , Transdução de Sinais/fisiologia , Ubiquitina-Proteína Ligases , Regulação para Cima
16.
Food Chem ; 315: 126295, 2020 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-32014671

RESUMO

Effect of nano-SiO2 packing on postharvest quality and antioxidant capacity of two different loquat cultivars (white-flesh 'Qingzhong' and red-flesh 'Dawuxing') were determined. Results showed that nano-SiO2 packing significantly inhibited internal browning, retarded the decline of total soluble solids, titratable acidity, ascorbic acid content and extractable juice in both cultivars. Decay index of nano-SiO2 packing in 'Dawuxing' and 'Qingzhong' was 53.25% and 42.84% lower than control after the day 12, respectively. Meanwhile, nano-SiO2 packing enhanced the contents of individual phenolic compounds and soluble sugar compounds, induced higher superoxide dismutase and catalase activities, which contributed to improving 1,1-diphenyl-2-picrylhydrazyl and hydroxyl radical scavenging capacity. Furthermore, the contents of total soluble solids, ascorbic acid and soluble sugar were higher in 'Qingzhong' than those in 'Dawuxing', which dedicated to better quality. These results indicated that nano-SiO2 packing was a promising approach in inhibiting decay, maintaining quality and expanding shelf life of loquats.


Assuntos
Antioxidantes/farmacologia , Eriobotrya/efeitos dos fármacos , Dióxido de Silício/farmacologia , Ácido Ascórbico/análise , Eriobotrya/química , Armazenamento de Alimentos , Frutas/química , Frutas/efeitos dos fármacos , Nanoestruturas , Fenóis/análise , Superóxido Dismutase/metabolismo , Temperatura
17.
Chem Biol Interact ; 319: 109024, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-32097614

RESUMO

Silicosis is an occupational pulmonary fibrosis that is caused by inhalation of silica (SiO2), and there are no effective drugs to treat this disease. Tanshinone IIA (Tan IIA), a natural product, has been reported to possess antioxidant and anti-fibrotic properties in various diseases. The purpose of the current study was to examine Tan IIA's protective effects against silica-induced pulmonary fibrosis and to explore the underlying mechanisms. We found that in vivo treatment with Tan IIA significantly relieved silica-induced lung fibrosis in a silicosis rat model by histological and immunohistochemical analyses. Further, in vitro mechanistic investigations, mainly using western blot and immunofluorescence analyses, revealed that Tan IIA administration markedly inhibited the silica-induced epithelial-mesenchymal transition (EMT) and transforming growth factor-ß1 (TGF-ß1)/Smad signaling pathway and also reduced silica-induced oxidative stress and activated the nuclear factor erythroid 2-related factor-2 (Nrf2) signaling pathway in A549 and human bronchial epithelial (HBE) cells. Furthermore, through transfection with siRNA, we demonstrate that Nrf2 activation partially mediates the suppression effects of Tan IIA on EMT and TGF-ß1/Smad signaling pathway activation induced by silica exposure, thus mediating the anti-fibrotic effects of Tan IIA against silica-induced pulmonary fibrosis. In our study, Tan IIA has been identified as a possible anti-oxidative and anti-fibrotic drug for silicosis.


Assuntos
Abietanos/farmacologia , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Fator 2 Relacionado a NF-E2/metabolismo , Fibrose Pulmonar/tratamento farmacológico , Transdução de Sinais/efeitos dos fármacos , Proteínas Smad/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Células A549 , Animais , Antioxidantes/metabolismo , Linhagem Celular , Linhagem Celular Tumoral , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Humanos , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Masculino , Fibrose Pulmonar/induzido quimicamente , Fibrose Pulmonar/metabolismo , Ratos , Ratos Sprague-Dawley , Dióxido de Silício/farmacologia
18.
Dalton Trans ; 49(7): 2209-2217, 2020 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-32003374

RESUMO

Photothermal therapy (PTT) is a promising treatment for tumors due to its efficiency and non-invasiveness. However, during the PTT treatment, reactive oxygen species (ROS) are produced in response to hyperthermia and thus harm the neighboring normal cells. In this work, a multifunctional theranostic agent (Se@SiO2@Au-PEG/DOX NCs) was exploited to solve this problem by introducing selenium, which can efficiently prevent normal cells from oxidative damage by scavenging reactive oxygen species during photothermal therapy. In addition, the Se@SiO2@Au-PEG/DOX nanocomposites (NCs) not only exhibited excellent properties of combined chemo-thermal synergistic therapy, but also showed no appreciable toxicity towards normal tissues due to the protective effect for continuous release of selenium. Thus, the fabricated Se@SiO2@Au-PEG/DOX NCs provide an integrated solution to overcome the limitations of selenium and PTT, and demonstrate great prospects as a safe and highly reliable theranostic agent.


Assuntos
Antibióticos Antineoplásicos/farmacologia , Doxorrubicina/farmacologia , Fotoquimioterapia , Nanomedicina Teranóstica , Células A549 , Animais , Antibióticos Antineoplásicos/síntese química , Antibióticos Antineoplásicos/química , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Técnicas de Cocultura , Doxorrubicina/síntese química , Doxorrubicina/química , Liberação Controlada de Fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Ouro/química , Ouro/farmacologia , Humanos , Camundongos , Polietilenoglicóis/química , Polietilenoglicóis/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Selênio/química , Selênio/farmacologia , Dióxido de Silício/química , Dióxido de Silício/farmacologia
19.
Artigo em Inglês | MEDLINE | ID: mdl-32035252

RESUMO

Chilling is one of the main abiotic stresses that adversely affect the productivity of sugarcane, in marginal tropical regions where chilling incidence occurs with seasonal changes. However, nanoparticles (NPs) have been tested as a mitigation strategy against diverse abiotic stresses. In this study, NPs such as silicon dioxide (nSiO2; 5-15 nm), zinc oxide (nZnO; <100 nm), selenium (nSe; 100 mesh), graphene (graphene nanoribbons [GNRs] alkyl functionalized; 2-15 µm × 40-250 nm) were applied as foliar sprays on sugarcane leaves to understand the amelioration effect of NPs against negative impact of chilling stress on photosynthesis and photoprotection. To this end, seedlings of moderately chilling tolerant sugarcane variety Guitang 49 was used for current study and spilt plot was used as statistical design. The changes in the level chilling tolerance after the application of NPs on Guitang 49 were compared with tolerance level of chilling tolerant variety Guitang 28. NPs treatments reduced the adverse effects of chilling by maintaining the maximum photochemical efficiency of PSII (Fv/Fm), maximum photo-oxidizable PSI (Pm), and photosynthetic gas exchange. Furthermore, application of NPs increased the content of light harvesting pigments (chlorophylls and cartinoids) in NPs treated seedlings. Higher carotenoid accumulation in leaves of NPs treated seedlings enhanced the nonphotochemical quenching (NPQ) of PSII. Among the NPs, nSiO2 showed higher amelioration effects and it can be used alone or in combination with other NPs to mitigate chilling stress in sugarcane.


Assuntos
Temperatura Baixa , Nanopartículas , Saccharum , Dióxido de Silício , Estresse Fisiológico , Clorofila/metabolismo , Nanopartículas/química , Fotossíntese/efeitos dos fármacos , Folhas de Planta/efeitos dos fármacos , Saccharum/efeitos dos fármacos , Plântula/efeitos dos fármacos , Dióxido de Silício/farmacologia , Estresse Fisiológico/efeitos dos fármacos
20.
Nanoscale ; 12(5): 3007-3018, 2020 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-31915777

RESUMO

Due to the increasing scientific and biomedical interest in various nanoparticles (NPs) with excellent properties and the onset of their commercial use, a convenient and adjustable physical method for improved efficiency needs to be used for enabling their tech-scale production. Recently, great progress has been made in the large-scale production of NPs with a simple structure by pulsed laser ablation in liquid (PLAL). In this work, we synthesized gold-silica core-shell NPs by improved PLAL and provided a guide on how to investigate their physico-chemical properties and association with biological effects towards cancer photothermal therapy (PTT). By means of this method, reproducible and scalable liquid phase NPs with less toxicity and good stability can be realized for tech-scale production based on its further adjustment and modification. Moreover, a more complete investigation of the associations between the physico-chemical properties of functional NPs with complex structure and their biological effects may enable more targeted NPs towards specific requirements of biomedical applications.


Assuntos
Hipertermia Induzida , Lasers , Nanopartículas , Neoplasias Experimentais/terapia , Fototerapia , Dióxido de Silício , Animais , Feminino , Células HeLa , Humanos , Células MCF-7 , Camundongos , Camundongos Endogâmicos BALB C , Nanopartículas/química , Nanopartículas/uso terapêutico , Neoplasias Experimentais/metabolismo , Neoplasias Experimentais/patologia , Dióxido de Silício/química , Dióxido de Silício/farmacologia
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