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1.
World J Gastrointest Oncol ; 16(5): 2038-2059, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38764836

RESUMO

BACKGROUND: Heterogeneous ribonucleoprotein A1 (hnRNPA1) has been reported to enhance the Warburg effect and promote colon cancer (CC) cell proliferation, but the role and mechanism of the miR-490-3p/hnRNPA1-b/PKM2 axis in CC have not yet been elucidated. AIM: To investigate the role and mechanism of a novel miR-490-3p/hnRNPA1-b/PKM2 axis in enhancing the Warburg effect and promoting CC cell proliferation through the PI3K/AKT pathway. METHODS: Paraffin-embedded pathological sections from 220 CC patients were collected and subjected to immunohistochemical analysis to determine the expression of hnRNPA1-b. The relationship between the expression values and the clinicopathological features of the patients was investigated. Differences in mRNA expression were analyzed using quantitative real-time polymerase chain reaction, while differences in protein expression were analyzed using western blot. Cell proliferation was evaluated using the cell counting kit-8 and 5-ethynyl-2'-deoxyuridine assays, and cell cycle and apoptosis were detected using flow cytometric assays. The targeted binding of miR-490-3p to hnRNPA1-b was validated using a dual luciferase reporter assay. The Warburg effect was evaluated by glucose uptake and lactic acid production assays. RESULTS: The expression of hnRNPA1-b was significantly increased in CC tissues and cells compared to normal controls (P < 0.05). Immunohistochemical results demonstrated significant variations in the expression of the hnRNPA1-b antigen in different stages of CC, including stage I, II-III, and IV. Furthermore, the clinicopathologic characterization revealed a significant correlation between hnRNPA1-b expression and clinical stage as well as T classification. HnRNPA1-b was found to enhance the Warburg effect through the PI3K/AKT pathway, thereby promoting proliferation of HCT116 and SW620 cells. However, the proliferation of HCT116 and SW620 cells was inhibited when miR-490-3p targeted and bound to hnRNPA1-b, effectively blocking the Warburg effect. CONCLUSION: These findings suggest that the novel miR-490-3p/hnRNPA1-b/PKM2 axis could provide a new strategy for the diagnosis and treatment of CC.

2.
Materials (Basel) ; 17(10)2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38793365

RESUMO

The electrochemical splitting of seawater is promising but also challenging for sustainable hydrogen gas production. Herein, ZIF-67 nanosheets are grown on nickel foam and then etched by Ni2+ in situ to obtain a hierarchical hollow nanosheets structure, which demonstrates outstanding OER performance in alkaline seawater (355 mV at 100 mA cm-2). Diven by a silicon solar panel, an overall electrolysis energy efficiency of 62% is achieved at a high current of 100 mA cm-2 in seawater electrolytes. This work provides a new design route for improving the catalytic activity of metal organic framework materials.

3.
Front Neurol ; 14: 1189076, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38090272

RESUMO

Introduction: Insomnia is the most common form of sleep deprivation (SD) observed in clinics. Although there are differences between insomnia and SD, they have similar symptoms and the same animal model. Currently, there is a lack of microarray data on insomnia. Therefore, for now, we are going to apply the SD data to insomnia. Although many studies have explained the possible mechanisms associated with insomnia, no previous studies have considered the key genes associated with insomnia or the relationship between insomnia and immune cells. In this study, we analyzed the relationship between key genes and immune cells by identifying biomarkers for the diagnosis of insomnia. Next, we verified the efficacy of these biomarkers experimentally. Methods: First, we downloaded four microarrays (GSE11755, GSE12624, GSE28750, and GSE48080) from the Gene Expression Omnibus (GEO) database, which included data from 239 normal human blood samples and 365 blood specimens from patients with SD. Then, we analyzed two groups of differentially expressed genes (DEGs) and used Support Vector Machine Recursive Feature Elimination (SVM-RFE) analysis and the Least Absolute Shrinkage and Selection Operator (LASSO) regression model to investigate these key genes. Next, we used CIBERSORT to investigate the composition of 22 immune cell components of key genes in SD patients. Finally, the expression levels of key biomarkers in sleep-deprived patients were examined by quantitative real-time polymerase chain reaction (qRT-PCR). Results: A total of 50 DEGs were identified: six genes were significantly upregulated, and 44 genes were significantly downregulated. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that Salmonella infection, NOD-like receptor (NLR) signaling pathway, Kaposi sarcoma-associated herpesvirus infection, and Th17 cell differentiation were significant. Based on machine learning, we identified C2CD2L, SPINT2, APOL3, PKNOX1, and A2M as key genes for SD; these were confirmed by receiver operating characteristic (ROC) analysis. Immune cell infiltration analysis showed that C2CD2L, SPINT2, APOL3, PKNOX1, and A2M were related in different degrees to regulatory T cells (Tregs), follicular T helper cells, CD8 cells, and other immune cells. The qRT-PCR experiments confirmed that the expression levels of C2CD2L concurred with the results derived from machine learning, but PKNOX1 and APOL3 did not. Discussion: In summary, we identified a key gene (C2CD2L) that may facilitate the development of biomarkers for insomnia.

4.
Front Immunol ; 14: 1087691, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37449204

RESUMO

Sepsis is a systemic inflammatory response syndrome caused by bacteria and other pathogenic microorganisms. Every year, approximately 31.5 million patients are diagnosed with sepsis, and approximately 5.3 million patients succumb to the disease. In this study, we identified biomarkers for diagnosing sepsis analyzed the relationships between genes and Immune cells that were differentially expressed in specimens from patients with sepsis compared to normal controls. Finally, We verified its effectiveness through animal experiments. Specifically, we analyzed datasets from four microarrays(GSE11755、GSE12624、GSE28750、GSE48080) that included 106 blood specimens from patients with sepsis and 69 normal human blood samples. SVM-RFE analysis and LASSO regression model were carried out to screen possible markers. The composition of 22 immune cell components in patients with sepsis were also determined using CIBERSORT. The expression level of the biomarkers in Sepsis was examined by the use of qRT-PCR and Western Blot (WB). We identified 50 differentially expressed genes between the cohorts, including 2 significantly upregulated and 48 significantly downregulated genes, and KEGG pathway analysis identified Salmonella infection, human T cell leukemia virus 1 infection, Epstein-Barr virus infection, hepatitis B, lysosome and other pathways that were significantly enriched in blood from patients with sepsis. Ultimately, we identified COMMD9, CSF3R, and NUB1 as genes that could potentially be used as biomarkers to predict sepsis, which we confirmed by ROC analysis. Further, we identified a correlation between the expression of these three genes and immune infiltrate composition. Immune cell infiltration analysis revealed that COMMD9 was correlated with T cells regulatory (Tregs), T cells follicular helper, T cells CD8, et al. CSF3R was correlated with T cells regulatory (Tregs), T cells follicular helper, T cells CD8, et al. NUB1 was correlated with T cells regulatory (Tregs), T cells gamma delta, T cells follicular helper, et al. Taken together, our findings identify potential new diagnostic markers for sepsis that shed light on novel mechanisms of disease pathogenesis and, therefore, may offer opportunities for therapeutic intervention.


Assuntos
Infecções por Vírus Epstein-Barr , Sepse , Animais , Humanos , Herpesvirus Humano 4 , Sepse/diagnóstico , Sepse/genética , Biomarcadores , Biologia Computacional , Aprendizado de Máquina , Proteínas Adaptadoras de Transdução de Sinal
5.
Cancer Rep (Hoboken) ; 6(5): e1808, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-37092360

RESUMO

BACKGROUND: This study aimed to identify genes related to the degree of immune cell infiltration in head and neck squamous cell carcinoma (HNSCC), explore their new biological functions, and evaluate their diagnostic and prognostic value in HNSCC. METHODS: Transcriptomic data from The Cancer Genome Atlas (TCGA) HNSCC dataset was used to screen differentially expressed genes between tumors and normal tissues, followed by weighted correlation network analysis (WGCNA) to identify immune-related modules. Differential gene expression, immune cell infiltration, and survival analyses were performed to screen key genes. The expression of these key genes was validated in Oncomine and gene expression omnibus (GEO) datasets and by immunohistochemistry (IHC). RESULTS: 1869 and 1578 genes were significantly upregulated and downregulated in HNSCC. WGCNA showed that the brown module was associated with the most significant number of immune-related genes. PPI network analysis demonstrated that PPL, SCEL, KRT4, KRT24, KRT78, KRT13, SPRR3, TGM3, CRCT1, and CRNN were key components in the brown module. Furthermore, the expression levels of KRT4, KRT78, KRT13, and SPRR3 in HNSCC correlated with infiltration levels of CD8+ T cells and macrophages. Survival analyses revealed that the expression of KRT78, KRT13, and SPRR3 in HNSCC correlated with overall survival (OS). The IHC assay indicated that KRT13 (p = .042), KRT78 (p < .001), and SPRR3 (p = .022) protein expression levels in HNSCC were significantly lower than in normal tissues. Analysis of GSE65858 and GSE41613 datasets showed that a worse OS was associated with low expression of KRT78 (p = .0086, and p = .005) and SPRR3 (p = .017, and p = .02). CONCLUSIONS: Our findings suggest that KRT4, KRT78, KRT13, and SPRR3 are related to the occurrence and development of HNSCC. Importantly, KRT78 and SPRR3 might serve as diagnostic and prognostic biomarkers of HNSCC.


Assuntos
Neoplasias de Cabeça e Pescoço , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/genética , Regulação Neoplásica da Expressão Gênica , Perfilação da Expressão Gênica , Transcriptoma , Transglutaminases/genética
6.
J Colloid Interface Sci ; 630(Pt A): 204-211, 2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-36242880

RESUMO

Aluminum sulfide is a novel light metal sulfide, which possesses multiple advantages for lithium storage, including high theoretical capacity, proper discharge potential and good conductivity. However, much research has not been done in areas related to light metal sulfide materials. Herein, we synthesized Al2S3/C nanocomposite by a facile one-step ball milling method. This simple method not only effectively achieves the uniform composite of Al2S3 nanoparticles and carbon sheets, but also controls Al2S3 into ultrafine nanocrystals. Al2S3/C electrode demonstrates very outstanding lithium storage performance with large reversible specific capacity (1249 mAh g-1 at 100 mA g-1), remarkable rate capability (670 mAh g-1 at 5000 mA g-1) and superior long-cycling stability (retaining 850 mAh g-1 even after 1000 cycles at 1000 mA g-1). Moreover, the reversible lithium storage behavior and excellent diffusion kinetics of Al2S3/C are unveiled deeply. This work provides an inspiration to develop new light metal sulfide materials for the next-generation high-performance lithium ion battery.

7.
Bioengineered ; 13(3): 6740-6749, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35246004

RESUMO

Sepsis brain injury (SBI) is a major cause of death in critically ill patients. The present study aimed to investigate the role of emodin in SBI development. Human astrocyte 1321N1 cells were stimulated with 100 ng/mL lipopolysaccharide (LPS) to establish an SBI model in vitro. Flow cytometry was performed to measure the cell pyroptosis. The protein expression levels of syndecan-1 (SDC-1), NLR family pyrin domain containing 3 (NLRP3), Caspase-1, and the N-terminal fragment of gasdermin D (GSDMD-N) were measured using Western blotting. Interleukin (IL)-1ß, IL-6, IL-10, and tumor necrosis factor (TNF)-α levels in cells were measured using enzyme-linked immunosorbent assay kits. The N6-methyladenosine (m6A) modification was analyzed using the methylated RNA immunoprecipitation assay. NLRP3 activator, nigericin, was used to overexpress NLRP3. LPS treatment significantly enhanced the pyroptosis in 1321N1 cells, increased the levels of TNF-α, IL-1ß, and IL-6, and decreased the levels of IL-10. The protein expression levels of NLRP3, SDC-1, GSDMD-N, and Caspase-1 were also increased. Emodin treatment decreased the levels of TNF-α, IL-1ß, IL-6, NLRP3, SDC-1, GSDMD-N, and Caspase-1, while increasing the levels of IL-10 in LPS-treated 1321N1 cells. Nigericin reversed the effects of emodin. Furthermore, emodin upregulated m6A levels in NLRP3 by increasing the expression of methyltransferase-like 3 (METTL3). Meanwhile, knockdown of METTL3 reversed the effects of emodin on the mRNA expression and stability of NLRP3. Therefore, emodin inhibits the inflammation and pyroptosis of LPS-treated 1321N1 cells by inactivating METTL3-mediated NLRP3 expression.


Assuntos
Emodina , Lipopolissacarídeos , Caspase 1/metabolismo , Caspase 1/farmacologia , Emodina/farmacologia , Humanos , Inflamação/metabolismo , Interleucina-10/farmacologia , Interleucina-6 , Lipopolissacarídeos/farmacologia , Metiltransferases/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Nigericina/farmacologia , Domínio Pirina , Piroptose/fisiologia , Fator de Necrose Tumoral alfa
8.
Spectrochim Acta A Mol Biomol Spectrosc ; 264: 120263, 2022 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-34454132

RESUMO

As a main extracellular metabolite of dopamine, 3-methoxytyramine (3-MT) is considered a potential biomarker of pheochromocytomas and paragangliomas. Therefore, the determination of 3-MT is of great significance in the early diagnosis of disease. However, it remains challenging for detecting 3-MT in consideration of sensitivity and accuracy. Here, a luminescent  Eu3+ functionalized metal-organic frameworks (Eu3+@Al-MOF)with ultra-high chemical stability was constructed based on postsynthetic modification. Such a rational design greatly enhances the fluorescence signal of Eu3+@Al-MOF and it is endowed with excellent properties as a luminescent sensor to detect 3-MT in urine system. Intriguingly, the strong red emitting derived from antenna effect was significantly interdicted upon addition of 3-MT through the interaction between 3-MT and the ligand. The proposed sensing system exhibited many appealing analytical performances, such as excellent selectivity, high sensitivity and quick response. Remarkably, the developed paper-based sensor not only provides a portable and reliable strategy for direct detection of 3-MT but also expands the application of visual analysis tools. This work represents the first effort in designing a luminescent sensor to determine the metabolite biomarker 3-MT level and provides a new method for biomedical analysis.


Assuntos
Neoplasias das Glândulas Suprarrenais , Elementos da Série dos Lantanídeos , Estruturas Metalorgânicas , Feocromocitoma , Neoplasias das Glândulas Suprarrenais/diagnóstico , Diagnóstico Precoce , Európio , Humanos
9.
ACS Appl Mater Interfaces ; 13(49): 59164-59173, 2021 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-34851097

RESUMO

Near-infrared window II (NIR-II, 1000-1700 nm) imaging displays the advantages in deep-tissue high-contrast imaging in vivo on the strength of the high temporal-spatial resolution and deeper penetration. However, the clinical utility of NIR-II imaging agents is limited by their single function. Herein, for the first time, we report the design of a multifunctional drug delivery system (DDS) assembly, CQ/Nd-MOF@HA nanohybrids, with NIR-II fluorescence (1067 nm), large Stokes shifts, and ultrahigh quantum yield, which combined targeted NIR-II luminescence bioimaging and pH-controlled drug delivery. The nanoscale metal-organic framework (MOF) as a highly promising multifunctional DDS for targeted NIR-II bioimaging and chemotherapy in vitro and in vivo lays the foundation of the MOF-based DDS for further clinical diagnosis and treatment.


Assuntos
Antineoplásicos/farmacologia , Ácido Hialurônico/farmacologia , Estruturas Metalorgânicas/farmacologia , Neodímio/farmacologia , Imagem Óptica , Neoplasias Ovarianas/diagnóstico por imagem , Neoplasias Ovarianas/tratamento farmacológico , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Sistemas de Liberação de Medicamentos , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Humanos , Ácido Hialurônico/química , Concentração de Íons de Hidrogênio , Raios Infravermelhos , Masculino , Teste de Materiais , Estruturas Metalorgânicas/síntese química , Estruturas Metalorgânicas/química , Camundongos , Camundongos Endogâmicos BALB C , Neodímio/química , Neoplasias Experimentais/diagnóstico por imagem , Neoplasias Experimentais/tratamento farmacológico , Tamanho da Partícula , Propriedades de Superfície , Células Tumorais Cultivadas
10.
Dalton Trans ; 50(43): 15870-15877, 2021 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-34709256

RESUMO

Nanocatalytic cancer therapy based on chemodynamic therapy, which converts hydrogen peroxide (H2O2) into toxic reactive oxygen species via the Fenton-like reaction, is regarded as a promising therapeutic strategy due to its specific response toward the tumor microenvironment (TME). However, the H2O2 concentration in TME (100 µM to 1 mM) is insufficient and introducing enough H2O2 or H2O2-generating agents is challenging. In view of this, we report a drug delivery system, CaO2/DOX@Cu/ZIF-8@HA (CDZH), which is capable of targeted H2O2 self-supply and exhibits outstanding chemo/chemodynamic synergetic therapy capability. CaO2/DOX@Cu/ZIF-8@HA is synthesized by fabricating biodegradable Cu/ZIF-8 shell-encapsulated CaO2 nanoparticles, loading chemotherapy drug doxorubicin, and coating a hyaluronic acid shell. In an acidic tumor microenvironment, the CDZH nanostructures targeted the release of doxorubicin, Cu2+, and CaO2. Doxorubicin affects chemotherapy and bioimaging, and CaO2 supplies H2O2 through a Cu-Fenton-like reaction to generate hydroxyl radicals with high oxidation activity for chemodynamic therapy. In brief, the drug delivery system combined targeted H2O2 self-supply and targeted bioimaging possess the potential of an efficient synergistic strategy for chemodynamic therapy and chemotherapy.


Assuntos
Estruturas Metalorgânicas
11.
Nanotechnology ; 32(39)2021 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-34126599

RESUMO

Sodium-ion batteries (SIBs) are expected to be a great substitute for lithium ion batteries. Although there are many difficulties to overcome, SIBs have become one of the most important research areas for large-scale energy storage equipment. The spherical particles are conducive to the contact between the cathode material and the electrolyte, which could increase the electrochemical reaction area, and improve the deintercalation rate of sodium ions during charging and discharging. In this paper, a precipitation method was used to prepare spherical MnCO3material as template and raw material. After all the raw materials were weighed with the molar ratios of Na0.67Mn0.67-0.75xNi0.33AlxO2, a series of hollow micro-spherical sodium-ion cathode materials were synthesized by the conventional high-temperature solid-state method. The effects of Al-doped on the structure and electrochemical performance of Na0.67Ni0.33Mn0.67O2was studied, and it was founded that the samples doped with Al had smaller particle size than that without Al. The electrochemical tests showed that Na0.67Mn0.595Ni0.33Al0.1O2(x= 0.1) exhibite superior high-rate capabilities and cyclic stability. And the hollow microsphere structure has a higher capacity, the first discharge capacity at 0.1C reach 128 mAh g-1.

12.
Oncol Lett ; 21(4): 245, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33664809

RESUMO

Diffuse large B-cell lymphoma (DLBCL) is the most common and heterogeneous lymphoid malignancy. The subtype with MYC and BCL-2 double-expressor lymphoma (DEL) was defined by its aggressive nature and poor survival outcome. Therefore, the development of effective therapies for the DEL subtype is imperative. Fatty acid synthase (FASN) activity is associated with altered lipid metabolism and aberrant protein translation in DLBCL. However, the inter-regulation of these key processes is not fully determined in DEL. In the present study, the clinical and biological impact of FASN was investigated in the DEL subtype. Initially, FASN expression levels were analyzed from a patient cohort and the data indicated that the highest FASN expression was noted in DEL tissues compared with that noted in the DLBCL and reactive lymphoid hyperplasia tissues. Patients with DEL with combined high-FASN expression indicated poorer EFS outcomes than the rest of the patients. In vitro data indicated that FASN was overexpressed in SU-DHL-2 and U2932 cells. Silencing FASN decreased cell growth and promoted cell apoptosis by modulating the pERK/BCL-2 signaling pathway. In conclusion, the present study indicated that FASN was overexpressed in DEL and that its expression was associated with poor survival outcomes. Furthermore, the data demonstrated that FASN regulated the biological function via the pERK/BCL-2 signaling pathway. FASN serves a critical role in the progression of DEL and its expression may be associated with the development to a more aggressive phenotype of DLBCL. Therefore, it may be considered a potential therapeutic target for DLBCL.

13.
Ann Palliat Med ; 10(2): 2238-2253, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33725777

RESUMO

BACKGROUND: Abnormal microangiogenesis and microenvironmental disturbances within the Nasopharyngeal carcinoma (NPC) can exacerbate tumor hypoxia, which may increase radiotherapy resistance and thus lead to poor prognosis in NPC patients. A non-invasive imaging technique, dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), which can reflect the tumor blood perfusion and angiogenesis status, was used to investigate the relationships of DCE-MRI parameters with hypoxia-inducible factor 1 alpha (HIF-1α) expression and tumor grades in NPC patients. METHODS: 42 treatment-naive patients with pathologically confirmed NPC were enrolled in this analysis. Plain magnetic resonance scans and DCE-MRI scans were performed before treatment, and post-processing was performed to calculate the relative enhancement (RE), maximum relative enhancement (MRE), maximum enhancement (ME), wash-in rate (WIR), wash-out rate (WOR), time to peak (TTP), and area under the curve (AUC). Immunohistochemistry was used to detect HIF-1α expression in electronasopharyngeal fiberoscopic specimens. The clinical grade/stage of NPC was jointly assessed by an experienced radiologist and a radiotherapist. The potential correlations of the DCE-MRI parameters with HIF-1α expression and clinical grades were analyzed. The statistical analysis was performed using SPSS 17.0 software package. RESULTS: Among DCE-MRI parameters, RE, ME, and MRE were associated with the positive expression of HIF-lα in NPC and could reflect the hypoxic status in the local microenvironment of the cancer foci in vivo. RE, ME, and MRE were significantly higher in the positive HIF-1α expression group than in the negative HIF-1α expression group (F=5.281, P=0.027; F=11.923, P=0.001; F=6.228, P=0.017). RE, ME, and MRE were significantly correlated with clinical grade (F=3.646, P=0.021; F=3.204, P=0.034, F=3.050, P=0.040) and T stage (F=6.578, P=0.001; F=3.540, P=0.023; F=4.384, P=0.010). The values of RE, MRE, and ME gradually increased as the clinical grade and T stage increased. CONCLUSIONS: DCE-MRI is a valuable imaging technique for the noninvasive evaluation of hypoxia in NPC, the development of individualized treatment protocols, and the prediction of efficacy.


Assuntos
Meios de Contraste , Neoplasias Nasofaríngeas , Humanos , Hipóxia , Imageamento por Ressonância Magnética , Carcinoma Nasofaríngeo/diagnóstico por imagem , Carcinoma Nasofaríngeo/radioterapia , Neoplasias Nasofaríngeas/diagnóstico por imagem , Neoplasias Nasofaríngeas/radioterapia , Microambiente Tumoral
14.
Inorg Chem ; 60(3): 1664-1671, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33434431

RESUMO

Owing to their characteristic structures, metal-organic frameworks (MOFs) are considered as the leading candidate for drug-delivery materials. However, controlling the synthesis of MOFs with uniform morphology and high drug-loading/release efficiencies is still challenging, which greatly limits their applications and promotion. Herein, a multifunctional MOF-based drug-delivery system (DDS) with a controlled pore size of 100-200 nm for both therapeutic and bioimaging purposes was successfully synthesized in one step. Fe-MOF-based microcapsules were synthesized through a competitive coordination method, which was profited from the intrinsic coordination characteristics of the Fe element and the host-guest supramolecular interactions between Fe3+ and polyoxometalates anions. This as-synthesized macroporous DDS could greatly increase the drug-loading/release rate (77%; 83%) and serve as a magnetic resonance (MR) contrast agent. Because an Fe-containing macroporous DDS presents ultrahigh drug loading/release, the obtained 5-FU/Fe-MOF-based microcapsules displayed good biocompatibility, extremely powerful inhibition of tumor growth, and satisfactory MR imaging capability. Given all these advantages, this study integrates high therapeutic effect and diagnostic capability via a simple and effective morphology-controlling strategy, aiming at further facilitating the applications of MOFs in multifunctional drug delivery.


Assuntos
Antimetabólitos Antineoplásicos/farmacologia , Sistemas de Liberação de Medicamentos , Fluoruracila/farmacologia , Ferro/química , Estruturas Metalorgânicas/química , Animais , Antimetabólitos Antineoplásicos/química , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Portadores de Fármacos/química , Liberação Controlada de Fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Fluoruracila/química , Humanos , Estruturas Metalorgânicas/síntese química , Camundongos , Camundongos Nus , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Experimentais/patologia , Tamanho da Partícula , Porosidade , Propriedades de Superfície
15.
J Mater Chem B ; 8(26): 5707-5721, 2020 07 14.
Artigo em Inglês | MEDLINE | ID: mdl-32510093

RESUMO

Photodynamic therapy (PDT) is a light-based modality for tumor treatment that involves the generation of reactive oxygen species (ROS) by the combination of light, a photosensitizer, and molecular oxygen. Nevertheless, the therapeutic effects of PDT are limited by hypoxic conditions that worsen with oxygen consumption during the PDT process. Photo/chemodynamic therapy (PCDT) based on the Fenton reaction is one strategy to improve ROS generation, provided a highly effective Fenton reagent is developed. In this research, SiO2@Cu7S4 nanotubes (NTs) were synthesized as a PCDT agent. This double-valence metal-sulfide composite material can react with H2O2 at the tumor site. SiO2@Cu7S4 NTs can produce more ROS than the traditional PDT agents, and besides, they can also be used as a photothermal therapy (PTT) agent. SiO2@Cu7S4 NTs will trigger the PTT effect under 808 nm irradiation and generate a large amount of heat to eradicate cancer cells. This heat will also promote the PCDT effect by increasing the reaction rate. Thus, the SiO2@Cu7S4 NT is a suitable material for PCDT and PTT synergistic oncotherapy. The 808 nm laser is selected as the appropriate excitation source, providing adequate penetration and minimal harm to normal cells. The experimental data presented herein demonstrate the promising photosensitive, Fenton-like, and photothermal performance of SiO2@Cu7S4 NTs. Furthermore, the findings could promote the development of PCDT and PTT synergistic therapy. Thus, this research provides a feasible method to design a single, multifunctional material for cancer treatment.


Assuntos
Antineoplásicos/farmacologia , Cobre/farmacologia , Nanotubos/química , Fármacos Fotossensibilizantes/farmacologia , Fototerapia , Dióxido de Silício/farmacologia , Compostos de Enxofre/farmacologia , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Cobre/química , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Lasers , Camundongos , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Experimentais/metabolismo , Neoplasias Experimentais/patologia , Tamanho da Partícula , Fármacos Fotossensibilizantes/síntese química , Fármacos Fotossensibilizantes/química , Espécies Reativas de Oxigênio/metabolismo , Dióxido de Silício/química , Compostos de Enxofre/química , Propriedades de Superfície
16.
Dalton Trans ; 48(46): 17291-17297, 2019 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-31714562

RESUMO

Metal-organic frameworks (MOFs) are attractive in designing drug delivery systems for the treatment of cancer because of their unique porous properties. However, the search for multifunctional MOFs with high drug loading and magnetic resonance/fluorescence imaging capacities is still a challenge and they have rarely been reported. In this article, using the intrinsic advantages of MOFs, hollow Fe-MOFs with biomolecular grafting were fabricated and shown to be capable of loading much more drugs and exhibiting targeted drug delivery, pH-controlled drug release and magnetic resonance/fluorescence imaging. Benefiting from their hollow structures, the drug loading capacity is as high as 35%. Due to post-modification with folic acid (FA) and the fluorescent reagent (5-FAM) and the existence of Fe(iii), in vitro experiments indicate that Fe-MOF-5-NH2-FA-5-FAM/5-FU can target cancer cells HepG-2 and display excellent magnetic resonance/fluorescence imaging. Furthermore, in vivo biodistribution indicates that Fe-MOF-5-NH2-FA-5-FAM/5-FU can accumulate in the tumor. Taken together, our work integrates high drug loading and bioimaging into a single MOF successfully and reveals the enormous potential of the functionalized MOF for drug delivery and bioimaging.


Assuntos
Portadores de Fármacos/química , Imageamento por Ressonância Magnética/métodos , Estruturas Metalorgânicas/química , Imagem Multimodal/métodos , Imagem Óptica/métodos , Liberação Controlada de Fármacos , Fluoruracila/química , Fluoruracila/metabolismo , Ácido Fólico/química , Células Hep G2 , Humanos
17.
Analyst ; 144(19): 5875-5881, 2019 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-31486467

RESUMO

A unique metal-organic framework with the formula [Cd4(H2L)2(L)·H2O]·3H2O (H4L = 5,5'-(1H-1,2,4-triazole-3,5-diyl)diisophthalic acid) was successfully constructed under solvothermal conditions. The frameworks with multiple free Lewis base sites and Lewis acid sites exhibited easily sensitized properties. After the encapsulation of Tb3+ cations, the as-synthesized Tb3+@Cd-MOF demonstrated strong luminescence induced by the efficient energy transfer from the bridging ligands to the Tb3+ cations, with the potential to serve as a chemical sensor. Interestingly, Tb3+@Cd-MOF was proven to be a very promising and highly selective and sensitive luminescent platform for the quantitative detection of arginine, which is the biomarker of cystinuria. The fluorescent probe presented high selectivity to arginine in urine with strong luminescence quenching. Furthermore, a convenient fluorescence-based test paper for the visual detection of arginine in applications was prepared. For the first time, arginine was quantified and monitored in urine by a highly efficient recyclable fluorescent sensor based on Tb3+-functionalized MOF hybrids, which may be a potential candidate for the further development of clinical diagnostic tools.


Assuntos
Arginina/urina , Corantes Fluorescentes/química , Estruturas Metalorgânicas/química , Térbio/química , Biomarcadores/urina , Cistinúria/diagnóstico , Fluorescência , Corantes Fluorescentes/síntese química , Humanos , Limite de Detecção , Estruturas Metalorgânicas/síntese química , Espectrometria de Fluorescência/métodos
18.
Chem Commun (Camb) ; 55(29): 4202-4205, 2019 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-30896000

RESUMO

While nickel phosphide is a highly attractive catalyst for the hydrogen evolution reaction, its preparation requires either high temperature or the use of highly toxic PH3 directly or indirectly. Herein, we demonstrate that H2 plasma activated red phosphorus enables the synthesis of self-supported Ni2P nanosheet (Ni2P/NF) arrays on commercial nickel foam from a NiO/NF precursor at only 250 °C. Highly reactive atomic H in the plasma induces dissociation of the P4 molecules, yielding an acid stable electrode with excellent hydrogen evolution activity and good mechanical strength.

19.
Nanoscale ; 10(13): 6205-6211, 2018 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-29560986

RESUMO

Benefiting from their porous structures, metal-organic frameworks (MOFs) have attracted intensive attention for use in drug release. However, the controllable synthesis of MOFs with proper particle sizes is still very challenging, which largely limits its applications. Here, UIO-66-NH2 with controlled particle sizes in the range of 20-200 nm has been achieved successfully. The amine on UIO-66-NH2 is demonstrated for the feasible post-modifying of UIO-66-NH2 to obtain multifunctional MOFs, overcoming the limitations of functional simplicity and broadening the range of applications. After covalent grafting the targeting reagent folic acid (FA) and the fluorescence imaging agent 5-carboxyfluorescein (5-FAM), UIO-66-NH2-FA-5-FAM/5-FU can target the cancer cells HePG-2 and display excellent fluorescence imaging in vitro. Moreover, the in vivo biodistribution and antitumor assays indicate that UIO-66-NH2-FA-5-FAM/5-FU can accumulate in the tumor and display stronger antitumor efficiency due to the long-time drug release. Taken together, this study integrates the imaging section and the treated section in a single platform successfully and the present approach can be a good use of therapeutic MOFs to achieve the desired objective, a better treatment.


Assuntos
Antineoplásicos/administração & dosagem , Liberação Controlada de Fármacos , Estruturas Metalorgânicas/química , Neoplasias/tratamento farmacológico , Ácido Fólico , Células Hep G2 , Humanos , Tamanho da Partícula , Distribuição Tecidual
20.
ACS Appl Mater Interfaces ; 9(4): 3455-3462, 2017 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-28079361

RESUMO

As a result of their extraordinarily large surfaces and well-defined pores, the design of a multifunctional metal-organic framework (MOF) is crucial for drug delivery but has rarely been reported. In this paper, a novel drug delivery system (DDS) based on nanoscale MOF was developed for use in cancer diagnosis and therapy. This MOF-based tumor targeting DDS was fabricated by a simple postsynthetic surface modification process. First, magnetic mesoporous nanomaterial Fe-MIL-53-NH2 was used for encapsulating the drug and served as a magnetic resonance contrast agent. Moreover, the Fe-MIL-53-NH2 nanomaterial exhibited a high loading capacity for the model anticancer drug 5-fluorouracil (5-FU). Subsequently, the fluorescence imaging agent 5-carboxyfluorescein (5-FAM) and the targeting reagent folic acid (FA) were conjugated to the 5-FU-loaded Fe-MIL-53-NH2, resulting in the advanced DDS Fe-MIL-53-NH2-FA-5-FAM/5-FU. Owing to the multifunctional surface modification, the obtained DDS Fe-MIL-53-NH2-FA-5-FAM/5-FU shows good biocompatibility, tumor enhanced cellular uptake, strong cancer cell growth inhibitory effect, excellent fluorescence imaging, and outstanding magnetic resonance imaging capability. Taken together, this study integrates diagnostic and treatment aspects into a single platform by a simple and efficient strategy, aiming for facilitating new possibilities for MOF use for multifunctional drug delivery.


Assuntos
Estruturas Metalorgânicas/química , Antineoplásicos , Sistemas de Liberação de Medicamentos , Imageamento por Ressonância Magnética , Espectroscopia de Ressonância Magnética
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