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1.
Mikrochim Acta ; 191(2): 117, 2024 01 31.
Artículo en Inglés | MEDLINE | ID: mdl-38294558

RESUMEN

A simple and effective pepsin detection assay is reported based on a pepsin-susceptible peptide (PSP) reporter degradation strategy. PSP, which can be specifically cleaved by pepsin, was modified with fluorescein isothiocyanate (FITC) and biotin at the N- and C-terminals to be used as a reporter for colorimetric detection of dipsticks. A universal lateral flow dipstick consisting of a streptavidin test line for biotin binding and a sample pad immobilized with a gold-labeled polyclonal (rabbit) anti-FITC antibody was used to verify PSP-based pepsin detection. When the PSP reporter reacts with pepsin in a tube, it cleaves into two fragments, and the cleaved fragments do not display any color on the test line. Therefore, the higher the concentration of pepsin is, the greater is the decrease in test line intensity (IT-line) and the higher is the control line intensity (IC-line). First, the PSP cleavage and dipstick assay conditions for pepsin detection was optimized. The ratio of color intensity (IT-line/IC-line) of PSP-based dipstick assay showed a linear relationship with log concentration of pepsin ranging between 4 and 500 ng/mL (R2 = 0.98, n = 6), with a limit of detection of 1.4 ng/mL. It also exhibited high specificity and good reproducibility. Finally, pepsin levels were quantified in saliva samples from healthy controls (n = 34) and patients with laryngopharyngeal reflux (LPR, n = 61). Salivary pepsin levels were higher in patients with LPR than in healthy controls. The salivary pepsin levels correlated with those measured using a conventional enzyme-linked immunosorbent assay kit. Therefore, this PSP-based dipstick assay is a convenient tool for assessing salivary pepsin levels.


Asunto(s)
Biotina , Colorimetría , Isotiocianatos , Animales , Humanos , Conejos , Estudios Transversales , Pepsina A , Estudios Prospectivos , Reproducibilidad de los Resultados , Saliva , Fluoresceína , Péptidos
2.
Molecules ; 29(16)2024 Aug 21.
Artículo en Inglés | MEDLINE | ID: mdl-39203013

RESUMEN

Biofumigation was proposed as an alternative to synthetic pesticides for the disinfection of agricultural soils, in view of the biocidal effect of isothiocyanates (ITCs) released by some vegetal species, like Brassicaceae. However, biofumigation also presents limitations; thus, a novel and viable alternative could be the direct introduction of ITCs into agricultural soils as components loaded into biodegradable hydrogels. Thus, in this work, ITCs-based microemulsions were developed, which can be loaded into porous polymer-based hydrogel beads based on sodium alginate (ALG) or sodium carboxymethyl cellulose (CMC). Three ITCs (ethyl, phenyl, and allyl isothiocyanate) and three different surfactants (sodium dodecylsulfate, Brij 35, and Tween 80) were considered. The optimal system was characterized with attenuated ATR-FTIR spectroscopy and differential scanning calorimetry to study how the microemulsion/gels interaction affects the gel properties, such as the equilibrium water content or free water index. Finally, loading and release profiles were studied by means of UV-Vis spectrophotometry. It was found that CMC hydrogel beads showed a slightly more efficient profile of micelles' release in water with respect to ALG beads. For this reason, and due to the enhanced contribution of Fe(III) to their biocidal properties, CMC-based hydrogels are the most promising in view of the application on real agricultural soils.


Asunto(s)
Emulsiones , Hidrogeles , Isotiocianatos , Suelo , Hidrogeles/química , Emulsiones/química , Isotiocianatos/química , Isotiocianatos/farmacología , Suelo/química , Agricultura , Materiales Biocompatibles/química , Alginatos/química , Fertilizantes , Carboximetilcelulosa de Sodio/química
3.
Cell Biochem Funct ; 40(7): 683-693, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-35924674

RESUMEN

Mouse strains can have divergent basal bone mass, yet this phenotype is seldom reflected in the design of studies seeking to identify new modulators of bone resorption by osteoclasts. Sulforaphane exerts inhibitory effects on in vitro osteoclastogenesis in cells from C57BL/6 mice. Here, we explore whether a divergent basal bone mass in different mouse strains is linked both to in vitro osteoclastogenic potential and to SFX-01 sensitivity. Accordingly, osteoclasts isolated from the bone marrow (BM) of C57BL/6, STR/Ort and CBA mice with low, high, and intermediate bone mass, respectively, were cultured under conditions to promote osteoclast differentiation and resorption; they were also treated with chemically stabilised sulforaphane (SFX-01) and respective sensitivity to inhibition evaluated by counting osteoclast number/resorption activity on dentine discs. We observed that osteoclastogenesis exhibited different macrophage colony-stimulating factor/receptor activator of nuclear factor kappa-Β ligand sensitivity in these mouse strains, with cells from C57BL/6 and CBA generating higher osteoclast numbers than STR/Ort; the latter formed only half as many mature osteoclasts. We found that 100 nM SFX-01 exerted a potent and significant reduction in osteoclast number and resorptive activity in cells derived from C57BL/6 mice. In contrast, 10-fold higher SFX-01 concentrations were required for similar inhibition in CBA-derived cells and, strikingly, a further 2.5-fold greater concentration was required for significant restriction of osteoclast formation/function in STR/Ort. These data are consistent with the notion that the BM osteoclast precursor population contributes to the relative differences in mouse bone mass and that mice with higher bone mass exhibit lower in vitro osteoclastogenic potential as well as reduced sensitivity to inhibition by SFX-01.


Asunto(s)
Resorción Ósea , Osteoclastos , Animales , Resorción Ósea/tratamiento farmacológico , Diferenciación Celular , Células Cultivadas , Isotiocianatos , Ligandos , Factor Estimulante de Colonias de Macrófagos , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos CBA , Ligando RANK/farmacología , Sulfóxidos
4.
Shokuhin Eiseigaku Zasshi ; 62(3): 73-78, 2021.
Artículo en Japonés | MEDLINE | ID: mdl-34219099

RESUMEN

The main component of the Mustard and Horseradish extracts, which are used as natural food additives in Japan, is allyl isothiocyanate (AITC). The determination of AITC using GC-FID is the official method employed in the quality control assessments for these products. In this method, a commercially available AITC reagent is used as a calibrant. However, 1H-quantitative NMR (qNMR) analysis revealed that the AITC reagents contain impurity. Therefore, we examined the GC-FID and HPLC-refractive index detector (LC-RID) method based on relative molar sensitivities (RMSs) to high-purity single reference (SR). The RMSs of AITC/SR under the GC-FID and LC-RID conditions were accurately determined using qNMR. The AITC in two types of food additives was quantified using qNMR, SR GC-FID, and SR LC-RID methods. Both SR GC-FID and SR LC-RID showed good agreement within 2% with the AITC content determined by direct qNMR.


Asunto(s)
Armoracia , Planta de la Mostaza , Cromatografía Líquida de Alta Presión , Isotiocianatos , Japón , Diente Molar/química , Extractos Vegetales/análisis
5.
J Microencapsul ; 37(2): 91-108, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-31810417

RESUMEN

Aim: The optimisation and evaluation of ethosomal nanogel (NGs) for topical delivery in skin cancer.Methods: The formulations were optimised by employing 3-factor, 3-level Box Behnken design for responses of vesicle size, and fluxes. They characterised in vitro and evaluated for drug release, permeation and retention, skin penetration of ethosome, electron microscopy, texture analysis, and in vitro cytotoxicity.Results: The optimised formulation exhibited z-average 125.67 ± 10.43 nm, apparent zeta potential -17.1 ± 2.61 mV, average flux of drug loaded ethosome were 54.72 ± 5.45 and 59.83 ± 6.09 µg/cm2/h. Further, Rhodamine B loaded ethosome penetrated deeper up to 183.82 µm. The NGs texture analysis showed index of viscosity 225.45 g.s, firmness 209.34 g, cohesiveness -189.48 g, and consistency 59.45 g.s. The optimised ethosome NGs exhibited significant anti-cancer effect in B16-F10 murine tumour cell line (p < 0.05).Conclusion: Ethosomal NGs could be promising for skin cancer treatment.


Asunto(s)
Sistemas de Liberación de Medicamentos , Isotiocianatos , Melanoma Experimental/tratamiento farmacológico , Nanogeles , Neoplasias Cutáneas/tratamiento farmacológico , Administración Tópica , Ensayos de Selección de Medicamentos Antitumorales , Isotiocianatos/química , Isotiocianatos/farmacología , Melanoma Experimental/metabolismo , Melanoma Experimental/patología , Nanogeles/química , Nanogeles/uso terapéutico , Neoplasias Cutáneas/metabolismo , Neoplasias Cutáneas/patología , Sulfóxidos
6.
Chem Res Toxicol ; 32(4): 638-644, 2019 04 15.
Artículo en Inglés | MEDLINE | ID: mdl-30735032

RESUMEN

Benzyl isothiocyanate (BITC), a dietary isothiocyanate (ITC) derived from cruciferous vegetables, has anticancer properties. It is believed that the ITC moiety (-N═C═S) that reacts predominantly with thiol compounds plays a central role in triggering the activities resulting from these properties. Recent studies have demonstrated that ITCs also covalently modify amino moieties in a protein. In this study, we examined the chemical reaction between BITC and the aminophospholipid, phosphatidylethanolamine (PE), in the cell membrane or lipoprotein particle. To detect the BITC-modified PE, the bond between ethanolamine (EA) and phosphatidic acid in PE was cleaved using phospholipase D to form the BITC-EA adduct, which was then measured. BITC-EA was detected from the BITC-treated unilamellar liposome and low-density lipoprotein even with only a few micromoles of BITC treatment, suggesting that BITC might react with not only a thiol/amino group of a protein but also an amino moiety of an aminophospholipid. Moreover, after incorporating BITC-PE included in the liposomes into the cultured cells or after direct exposure of BITC to the cells, free BITC-EA was excreted and accumulated in the medium in a time-dependent manner. It indicates that an intracellular enzyme catalyzes the cleavage of BITC-PE to produce BITC-EA. Because the ITC-amine adduct is stable, the ITC-EA adduct could be a promising indicator of ITC exposure in vivo.


Asunto(s)
Etanolamina/metabolismo , Isotiocianatos/metabolismo , Fosfatidiletanolaminas/metabolismo , Animales , Etanolamina/análisis , Isotiocianatos/análisis , Liposomas/química , Liposomas/metabolismo , Ratones , Estructura Molecular , Fosfatidiletanolaminas/análisis , Células RAW 264.7
7.
Phys Chem Chem Phys ; 21(31): 17096-17108, 2019 Aug 21.
Artículo en Inglés | MEDLINE | ID: mdl-31339151

RESUMEN

The unique properties of silicon quantum dots (SQDs), including intriguing optical properties, biocompatibility, and ease of surface modification have made them excellent candidates for a variety of optoelectronic and biomedical applications. Unfortunately, the low quantum efficiency (QE), unstable photoluminescence, and poor colloidal stability of SQDs have hindered their wide applicability. Herein, we report the synthesis of four assemblies of SQDs (1.6-1.8 nm average diameter) functionalized with fluorescein dye through isothiocyanate (-NCS) and carboxylate (COO-) spacers in the benzene ring of the fluorescein to produce the dyads Am-SQD-Fl, DiAm-SQD-Fl, urea-SQD-Fl, and SQD-Fl. The photophysical measurements showed that the spacer played a key role in directing and controlling the optical properties of SQDs dyads, with the isothiocyanate spacer leading to a significant improvement in the QE of the dyad systems up to 65% and extending their photostability for at least one year. The interactions between the SQDs and fluorescein in the dyads Am-SQD-Fl, DiAm-SQD-Fl, and SQD-Fl were found to mainly proceed through photoinduced electron transfer at different rates, while energy transfer was confirmed to be the predominant process in the dyad urea-SQD-Fl. To demonstrate the suitability of the functionalized SQDs for bioimaging applications, the water-soluble dyads were examined for fluorescence imaging of human bone cancerous U2OS cells.


Asunto(s)
Materiales Biocompatibles/química , Colorantes Fluorescentes/química , Puntos Cuánticos/química , Silicio/química , Línea Celular Tumoral , Fluoresceínas/química , Humanos , Isotiocianatos/química , Cinética , Imagen Óptica , Tamaño de la Partícula , Solubilidad , Propiedades de Superficie
8.
Int J Mol Sci ; 20(23)2019 Nov 30.
Artículo en Inglés | MEDLINE | ID: mdl-31801206

RESUMEN

Inflammation is a common feature of many neurodegenerative diseases. The treatment of stem cells as a therapeutic approach to repair damage in the central nervous system represents a valid alternative. In this study, using Next-Generation Sequencing (NGS) technology, we analyzed the transcriptomic profile of human Gingival Mesenchymal Stem Cells (hGMSCs) treated with Moringin [4-(α-l-ramanosyloxy)-benzyl isothiocyanate] (hGMSCs-MOR) or with Cannabidiol (hGMSCs-CBD) at dose of 0.5 or 5 µM, respectively. Moreover, we compared their transcriptomic profiles in order to evaluate analogies and differences in pro- and anti-inflammatory pathways. The hGMSCs-MOR selectively downregulate TNF-α signaling from the beginning, reducing the expression of TNF-α receptor while hGMSCs-CBD limit its activity after the process started. The treatment with CBD downregulates the pro-inflammatory pathway mediated by the IL-1 family, including its receptor while MOR is less efficient. Furthermore, both the treatments are efficient in the IL-6 signaling. In particular, CBD reduces the effect of the pro-inflammatory JAK/STAT pathway while MOR enhances the pro-survival PI3K/AKT/mTOR. In addition, both hGMSCs-MOR and hGMSCs-CBD improve the anti-inflammatory activity enhancing the TGF-ß pathway.


Asunto(s)
Antiinflamatorios/farmacología , Cannabidiol/farmacología , Isotiocianatos/farmacología , Células Madre Mesenquimatosas/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Transcriptoma/efectos de los fármacos , Perfilación de la Expresión Génica , Regulación de la Expresión Génica , Encía/citología , Encía/efectos de los fármacos , Encía/inmunología , Humanos , Interleucina-1/genética , Interleucina-1/inmunología , Interleucina-6/genética , Interleucina-6/inmunología , Quinasas Janus/genética , Quinasas Janus/inmunología , Células Madre Mesenquimatosas/citología , Células Madre Mesenquimatosas/inmunología , Fosfatidilinositol 3-Quinasas/genética , Fosfatidilinositol 3-Quinasas/inmunología , Cultivo Primario de Células , Proteínas Proto-Oncogénicas c-akt/genética , Proteínas Proto-Oncogénicas c-akt/inmunología , Receptores de Interleucina-1/genética , Receptores de Interleucina-1/inmunología , Factores de Transcripción STAT/genética , Factores de Transcripción STAT/inmunología , Transducción de Señal/genética , Transducción de Señal/inmunología , Serina-Treonina Quinasas TOR/genética , Serina-Treonina Quinasas TOR/inmunología , Transcriptoma/inmunología , Factor de Crecimiento Transformador beta/genética , Factor de Crecimiento Transformador beta/inmunología , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/inmunología
9.
Molecules ; 24(4)2019 Feb 22.
Artículo en Inglés | MEDLINE | ID: mdl-30813352

RESUMEN

Lung cancer is the leading cause of cancer-related death in the Unites States, and approximately 85% of all lung cancers are classified as non-small cell lung cancer (NSCLC), which is extremely difficult to treat and its survival rate is low. After decades of clinical trials, the most effective treatments are still those that implement the first-generation platinum anticancer agent cisplatin (CDDP) in combination with other drugs. We previously demonstrated that the naturally-occurring compound phenethyl isothiocyanate (PEITC) can be used to sensitize NSCLC cells to CDDP. Furthermore, co-encapsulation of PEITC and CDDP in liposomes enhances their toxicity toward NSCLC cells. We here optimize liposomal-PEITC-CDDP, demonstrate the release of PEITC and CDDP from the nanoparticle, and show that liposomal-PEITC-CDDP is much more toxic toward both A549 and H596 human NSCLC cell lines than toward WI-38 and BEAS-2B human normal lung cell lines. Thus, we have prepared an efficacious therapy that has significantly higher toxicity toward cancer cell lines than normal cell lines.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Cisplatino/farmacología , Isotiocianatos/farmacología , Neoplasias Pulmonares/tratamiento farmacológico , Células A549 , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Composición de Medicamentos , Sinergismo Farmacológico , Humanos , Liposomas , Nanopartículas
10.
Br J Dermatol ; 177(2): 522-530, 2017 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-28295200

RESUMEN

BACKGROUND: Contact allergy to chloroprene rubber products is well known. Thiourea compounds are considered the cause of allergy. Diethylthiourea commonly occurs in this type of product and can decompose to the sensitizer ethyl isothiocyanate. OBJECTIVES: To investigate the clinical importance of degradation products and metabolites from organic thioureas in contact allergy to chloroprene rubber with a focus on isothiocyanates and isocyanates. METHODS: Patients with contact allergy to diphenylthiourea were patch tested with phenyl isothiocyanate and phenyl isocyanate. Patients with known contact allergy to diethylthiourea were retested with diethylthiourea, while chemical analyses of their chloroprene rubber products were performed. The stability of diethylthiourea, diphenylthiourea and dibutylthiourea in patch-test preparations was investigated. Liquid chromatography/mass spectrometry and solid-phase microextraction/gas chromatography were used for determination of organic thioureas and isothiocyanates. RESULTS: All patients allergic to diphenylthiourea reacted to phenyl isothiocyanate, two of eight reacted to phenyl isocyanate and six of eight reacted to diphenylthiourea. Four patients allergic to diethylthiourea reacted at retest; diethylthiourea was detected in all chloroprene rubber samples, with levels of 2-1200 nmol cm-2 . At 35 °C, ethyl isothiocyanate was emitted from all samples. Patch-test preparations of diethylthiourea, diphenylthiourea and dibutylthiourea all emitted the corresponding isothiocyanate, with diethylthiourea showing the highest rate of isothiocyanate emission. CONCLUSIONS: Thiourea compounds are degraded to isothiocyanates, which are generally strong or extreme sensitizers, thus acting as prehaptens. This process occurs in both chloroprene rubber products and patch-test preparations. Positive reactions to phenyl isocyanate indicate cutaneous metabolism, as the only known source of exposure to phenyl isocyanate is through bioactivation of diphenylthiourea.


Asunto(s)
Cloropreno/efectos adversos , Dermatitis Alérgica por Contacto/etiología , Isotiocianatos/efectos adversos , Goma/efectos adversos , Adulto , Cloropreno/química , Femenino , Haptenos/efectos adversos , Humanos , Isocianatos/efectos adversos , Masculino , Persona de Mediana Edad , Pruebas del Parche , Goma/química , Tiourea/efectos adversos , Tiourea/análogos & derivados , Tiourea/análisis
11.
J Microencapsul ; 34(3): 231-242, 2017 May.
Artículo en Inglés | MEDLINE | ID: mdl-28449614

RESUMEN

The objective of this study is to establish the ability of entrap allyl isothiocyanate (AITC) into polymeric nanoparticles to extend its shelf life and enhance its antiproliferative properties. Natural compounds, such as AITC, have showed multi-targeting activity resulting in a wide-range spectrum of therapeutic properties in chronic and degenerative diseases, conversely with most current pharmaceutical drugs showing single targeting activity and often result in drug resistance after extended administration periods. Apparently, AITC-loaded poly(lactic-co-glycolic acid) nanoparticles (PLGA NPs) reduced AITC degradation and volatility and were able to extend AITC shelf life compared with free AITC (65% vs. 20% in 24 h, respectively). Cell viability and uptake of AITC-loaded nanoparticles were studied in vitro, showing that the protection and sustained release of AITC from polymeric NPs involved a larger toxicity of tumoral cells. These nanoparticles could be used as protective systems for enhancing a biological activity.


Asunto(s)
Preparaciones de Acción Retardada , Portadores de Fármacos/química , Isotiocianatos/administración & dosificación , Ácido Láctico/química , Nanopartículas/química , Ácido Poliglicólico/química , Línea Celular Tumoral , Humanos , Copolímero de Ácido Poliláctico-Ácido Poliglicólico
12.
Pharm Dev Technol ; 22(5): 642-651, 2017 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-26916923

RESUMEN

PURPOSE: Among the potent anticancer agents, d,l-sulforaphane (SF) is very effective against many different types of cancer cells. Its clinical application is restricted because of its hydrophobicity, low gastrointestinal absorption and poor bioavailability. In the present study, a reliable micellar delivery system using monomethoxypoly (ethylene glycol)-poly (ɛ-caprolactone) (mPEG-PCL) was established. The encapsulation of SF inside mPEG-PCL as a nano-carrier was established and the cytotoxicity assay against human breast cancer cell line was evaluated. METHODS: In this study, SF was encapsulated within mPEG-PCL micelles through a single-step nano-precipitation method, leading to creation of SF-loaded mPEG-PCL (SF/mPEG-PCL) micelles. Di-block mPEG-PCL copolymers were synthesized and used to prepare micelles. MPEG-PCL copolymer was characterized by HNMR, FTIR, differential scanning calorimetry and gel permeation chromatography techniques. Characterization, stability of micelles, the particle size and morphology were determined. The release profile of the SF from the micelles which prepared by the drug-loaded copolymer, was evaluated. The cytotoxicity of free SF, mPEG-PCL and SF-loaded mPEG-PCL micelles was compared with each other by performing MTT assay of the treated MCF-7 cell line. Expression levels of BCL-2, MMP-9, BCL-XL, BAK, BAX and GAPDH (endogenous gene) as control were quantified by real time PCR. To evaluate the apoptotic effects of Free SF compared with SF-loaded mPEG-PCL micelles, flow cytometry analysis was done using the annexin V-FITC apoptosis detection kit. RESULTS: Our studies resulted in a successful establishment of uniformity and spherical SF-loaded mPEG-PCL micelles. The encapsulation efficiency of SF was 86 ± 1.58%. The results of atomic force microscopy revealed that the micelles have spherical shapes with size of 107 nm. In vitro release of SF from SF-entrapped micelles was remarkably sustained. The mPEG-PCL micelle showed little cytotoxicity in the case of MCF-7 cell line with concentration up to 1.5 mg/ml, whereas the SF-loaded mPEG-PCL micelles at all concentrations significantly was cytotoxic in the case of MCF-7 cell line. Finally, real-time PCR and flow cytometry were used to demonstrate that the SF-loaded mPEG-PCL could be efficiently inducing apoptosis in MCF-7 cell line. CONCLUSION: We achieved to a successful formulation of SF-loaded m-PEG/PCL micelles in this study. Based on the cytotoxicity results of mPEG-PCL micelles against human breast cancer cell line (MCF-7) in this study, it suggested that SF/mPEG-PCL micelles can be an effective breast cancer treatment strategy in the future.


Asunto(s)
Neoplasias de la Mama/tratamiento farmacológico , Portadores de Fármacos , Isotiocianatos/administración & dosificación , Poliésteres , Polietilenglicoles , Femenino , Humanos , Nanopartículas , Sulfóxidos
13.
Macromol Rapid Commun ; 37(18): 1533-9, 2016 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-27448182

RESUMEN

A facile strategy is presented to synthesize hyaluronic acid (HA) and a fluorescein isothiocyanate (FITC)-conjugated mesoporous silica nanocomposite (MSN) with multiple functions of fluorescence, tumor-cell targeting, pH-triggered gelation, and enzyme-responsive drug release. This injectable nanocomposite is able to indicate the entire tumor location and provides a microenvironment with rich anticancer drugs in and around tumor tissue for a long time, to avoid recrudescence. In this design, the mesoporous silica serves as the drug container, the FITC serves as a fluorescent probe, and the anchored HA plays multiple roles as drug-release cap, tumor-targeting points, and responsive gel matrix. Owing to the specific affinity between the HA on MSNs and the CD44 antigen over-expressed on tumor cells, the MSNs can selectively attach to tumor cells. The nanocomposites then exploit the pH-responsive interactions (hydrogen bonds) among the HA to self-assemble in situ into a hydrogel around the tumor tissue. The resulting hydrogel gradually releases its payload (doxorubicin, anticancer drugs)-loaded MSNs upon HA degradation in the presence of hyaluronidase-1 (Hyal-1), followed by endocytosis and intracellular drug release. All these properties have distinct benefits for tumor treatment, demonstrating that this device is a promising candidate for oncotherapy applications.


Asunto(s)
Antineoplásicos/administración & dosificación , Hidrogel de Polietilenoglicol-Dimetacrilato/química , Hidrogel de Polietilenoglicol-Dimetacrilato/metabolismo , Nanocompuestos/química , Neoplasias/tratamiento farmacológico , Neoplasias/metabolismo , Dióxido de Silicio/química , Antineoplásicos/farmacología , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Doxorrubicina/administración & dosificación , Doxorrubicina/farmacología , Humanos , Ácido Hialurónico/química , Hidrogel de Polietilenoglicol-Dimetacrilato/administración & dosificación , Concentración de Iones de Hidrógeno , Isotiocianatos/química , Tamaño de la Partícula , Porosidad , Relación Estructura-Actividad , Propiedades de Superficie
14.
Yao Xue Xue Bao ; 51(8): 1316-24, 2016 08.
Artículo en Zh | MEDLINE | ID: mdl-29906041

RESUMEN

The integrity of poly(ethylene glycol)-co-poly(ε-caprolactone) (PEG-PCL) micelles transcellular transported across madin-darby canine kidney(MDCK) epithelial cells was investigated. Fluorescein isothiocyanate isomer I(FITC) was conjugated to PEG-PCL and the product PEG-PCL-FITC was identified by fluorescence spectra. Two micelles were prepared using the thin-film hydration method: 3,3'-dioctadecyloxacarbocyanine perchlorate (DiO) and 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI) co-loaded PEG-PCL micelles (DiO-DiI-M), DiI loaded and PEG-PCL-FITC contained micelles(FITC-DiI-M). The size of the micelles was characterized by dynamic light scattering analysis using a Malvern Zetasizer Nano ZS and it turned out that the particle sizes of both micelles were about 30 nm with identical polydispersity index(PDI). The stability of the micelles in phosphate buffer saline(PBS) was monitored using fluorescence spectra and both micelles were stable within 4 h in PBS. The integrity of PEG-PCL micelles in the transcellular process across MDCK epithelial cell monolayer at 1 and 4 h was investigated using laser confocal scanning microscope and Förster resonance energy transfer(FRET) technology. The Person's coefficient and FRET efficiency of both Transwell layer and Receive layer were recorded. The results show that the FRET efficiency and Person's coefficient of the Receive layer was consistent with that of Transwell layer for both the micelles at 1 h, but decreased at 4 h and FITC-DiI-M decreased more significantly than Di O-DiI-M. The results indicated that the micelles could transport across the MDCK monolayer intactly at 1 h but some of them were disassembled during the 4 h transportation process.


Asunto(s)
Portadores de Fármacos/química , Transferencia Resonante de Energía de Fluorescencia , Micelas , Animales , Transporte Biológico , Caproatos , Perros , Humanos , Isotiocianatos , Lactonas , Células de Riñón Canino Madin Darby , Tamaño de la Partícula , Poliésteres , Polietilenglicoles
15.
Macromol Rapid Commun ; 36(16): 1511-20, 2015 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-26096462

RESUMEN

Hybrid rod-rod diblock copolymers, poly(γ-benzyl L-glutamate)-poly(4-cyano-benzoic acid 2-isopropyl-5-methyl-cyclohexyl ester) (PBLG-PPI), with determined chirality are facilely synthesized through sequential copolymerization of γ-benzyl-L-glutamate N-carboxyanhydride (BLG-NCA) and phenyl isocyanide monomers bearing chiral menthyl pendants using a Ni(cod)(bpy) complex as the catalyst in one-pot. Circular dichroism and absorption spectra reveal that each block of the block copolymers possesses a stable helical conformation with controlled helicity in solution due to the induction of chiral pendants. The two diastereomeric polymers self-assemble into helical nanofibrils with opposite handedness due to the different chiral induction of the L- and D-menthyl pendants, confirmed by transmission electron microscopy (TEM). Deprotection of the benzyl groups of the PBLG segment affords biocompatible amphiphilic diblock copolymers, poly(L-glutamic acid)-poly(4-cyano-benzoic acid 2-isopropyl-5-methyl-cyclohexyl ester) (PLGA-PPI), that can self-assemble into well-defined micelles by cosolvent induced aggregation. Very interestingly, a chiral rhodamine chromophores RhB(D) can be selectively encapsulated into the chiral polymeric micelles, which is efficiently internalized into living cells when directly monitored with a confocal microscope. This contribution will be useful for developing novel rod-rod biocompatible hybrid block copolymers with a controlled helicity, and may also provide unique chiral materials for potential bio-medical applications.


Asunto(s)
Anhídridos/química , Glutamatos/química , Imagen Molecular , Ácido Poliglutámico/análogos & derivados , Anhídridos/síntesis química , Materiales Biocompatibles/química , Rastreo Celular , Glutamatos/síntesis química , Humanos , Isotiocianatos/química , Conformación Molecular , Péptidos/química , Ácido Poliglutámico/síntesis química , Ácido Poliglutámico/química , Soluciones/química
16.
Contact Dermatitis ; 72(3): 139-46, 2015 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-25532938

RESUMEN

BACKGROUND: Exposure to chloroprene rubber has resulted in numerous cases of allergic contact dermatitis, attributed to organic thiourea compounds used as vulcanization accelerators. However, thiourea compounds are not considered to be strong haptens. OBJECTIVES: To analyse common commercial chloroprene materials for their contents of diethylthiourea (DETU), dibutylthiourea (DBTU), diphenylthiourea (DPTU), and their degradation products, isothiocyanates; and to investigate the sensitization potencies of possible degradation products of the mentioned thiourea compounds. METHODS: Liquid chromatography/mass spectrometry (MS) was used for quantification of organic thiourea compounds in chloroprene products, such as medical, sports and diving gear; isothiocyanates were measured by solid-phase microextraction/gas chromatography/MS. Sensitization potencies were determined with the murine local lymph node assay (LLNA). RESULTS: DETU was identified at concentrations of 2.7-9.4 µg/cm(2) in all samples, whereas neither DBTU nor DPTU was detected. At 37°C, degradation of DETU in the materials to ethyl isothiocyanate (EITC) was detected. EITC and ethyl isocyanate showed extreme and strong sensitization potencies, respectively, in the LLNA. CONCLUSIONS: DETU can act as a prehapten, being degraded to EITC when subjected to body temperature upon skin contact. EITC could thus be the culprit behind allergic contact dermatitis caused by chloroprene rubber.


Asunto(s)
Alérgenos/análisis , Dermatitis Alérgica por Contacto/etiología , Isotiocianatos/análisis , Neopreno/química , Tiourea/análogos & derivados , Alérgenos/inmunología , Humanos , Isotiocianatos/inmunología , Ensayo del Nódulo Linfático Local , Tiourea/análisis , Tiourea/inmunología
17.
Anal Chem ; 86(13): 6262-7, 2014 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-24873535

RESUMEN

We report a simple and rapid method for fabricating a surface-enhanced Raman scattering (SERS) substrate, which offers good flexibility, excellent optical transparency, and high SERS activity. Specifically, the SERS substrate (AuNPs/PMMA film) was obtained through self-assembly of gold nanoparticles (AuNPs) on newborn poly(methyl methacrylate) (PMMA) template. The UV-vis spectroscopy analysis and scanning electron microscopy observation revealed that the gold nanoparticles were closely assembled on the flexible and transparent PMMA template. The fabricated AuNPs/PMMA film SERS substrate allowed detection of model molecule, malachite green isothiocyanate, at a concentration as low as 0.1 nM, and exhibited good reproducibility in the SERS measurement. The Raman enhancement factor (EF) of the AuNPs/PMMA film was found to be as high as (2.4 ± 0.3) × 10(7). In addition, measure of residual malachite green on fish surface was carried out, and the result indicated that the AuNPs/PMMA film had great potential in the in situ ultrasensitive detection of analyte on irregular objects.


Asunto(s)
Colorantes/análisis , Oro/química , Isotiocianatos/análisis , Nanopartículas del Metal/química , Polimetil Metacrilato/química , Colorantes de Rosanilina/análisis , Espectrometría Raman/métodos , Límite de Detección , Nanopartículas del Metal/ultraestructura , Reproducibilidad de los Resultados , Propiedades de Superficie
18.
Chem Res Toxicol ; 27(6): 946-8, 2014 Jun 16.
Artículo en Inglés | MEDLINE | ID: mdl-24836554

RESUMEN

Naturally occurring phenethyl isothiocyanate (PEITC) was previously shown to sensitize human non-small cell lung cancer (NSCLC) cells to the platinum anticancer drug cisplatin (CDDP). Here, CDDP and PEITC were encapsulated in approximately 130 nm liposomes composed of 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC) and L-α-phosphatidylglycerol (EPG). The liposomal formulation enhanced the toxicity of this doublet (1:2 molar ratio of CDDP/PEITC) toward NCI-H596 NSCLC cells; the percent survival of cells was 30.2±6.2% after treatment with the nanoparticle formulation, compared to 50.9±3.5% when administered together free. Thus, such a treatment modality could prove useful in the clinic for the treatment of NSCLC.


Asunto(s)
Antineoplásicos/farmacología , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Cisplatino/farmacología , Sistemas de Liberación de Medicamentos , Isotiocianatos/farmacología , Neoplasias Pulmonares/tratamiento farmacológico , Nanopartículas/administración & dosificación , Antineoplásicos/administración & dosificación , Carcinoma de Pulmón de Células no Pequeñas/patología , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Cisplatino/administración & dosificación , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Isotiocianatos/administración & dosificación , Liposomas/administración & dosificación , Liposomas/química , Neoplasias Pulmonares/patología , Estructura Molecular , Nanopartículas/química , Tamaño de la Partícula , Relación Estructura-Actividad , Propiedades de Superficie
19.
Drug Dev Ind Pharm ; 40(4): 494-502, 2014 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-23611476

RESUMEN

CONTEXT: Sulforaphane (SFN) is a natural compound that has been investigated as a chemopreventive agent. SFN has been shown to inhibit the activator-protein-1 (AP-1) transcription factor and may be effective for inhibition of ultraviolet (UV) induced skin carcinogenesis. This study was designed to investigate the stability of SFN as a function of pH, temperature and in various solvents and formulations. MATERIALS AND METHODS: Stability was analyzed using high-performance liquid chromatography. A potential lead formulation was identified and evaluated in vivo. RESULTS: SFN was determined to undergo apparent first-order degradation kinetics for the conditions explored. It was observed that SFN undergoes base catalyzed degradation. Buffer species and solvent type impacts stability as well. SFN was found to be very sensitive to temperature with degradation rate changing by a factor of nearly 3.1 for every 10 °C change in temperature (at pH 4.0). SFN completely degraded after 30 days in a conventional pharmaceutical cream formulation. Improved stability was observed in organic formulation components. Stability studies were conducted on two nonaqueous topical formulations: a polyethylene glycol (PEG) ointment base and an organic oleaginous base. CONCLUSION: Topically applied SFN in the PEG base formulation significantly reduced AP-1 activation after UV stimulation in the skin of a transgenic mouse model, indicating that SFN in this formulation retains efficacy in vivo.


Asunto(s)
Anticarcinógenos/administración & dosificación , Isotiocianatos/administración & dosificación , Solventes/química , Factor de Transcripción AP-1/antagonistas & inhibidores , Administración Cutánea , Animales , Anticarcinógenos/química , Anticarcinógenos/farmacología , Cromatografía Líquida de Alta Presión , Estabilidad de Medicamentos , Almacenaje de Medicamentos , Femenino , Concentración de Iones de Hidrógeno , Isotiocianatos/química , Isotiocianatos/farmacología , Cinética , Ratones , Ratones Transgénicos , Polietilenglicoles/química , Piel/efectos de los fármacos , Piel/efectos de la radiación , Sulfóxidos , Temperatura , Factores de Tiempo , Rayos Ultravioleta/efectos adversos
20.
Int J Biol Macromol ; 259(Pt 1): 129203, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38184031

RESUMEN

Food safety is related to public health and environmental safety. Therefore, it is necessary to develop accurate and effective detection methods to assess food quality and safety. In this study, a pH-responsive functional film (BC/GA/FITC/PCA) was generated for the real-time and visual monitoring of shrimp freshness. Bacterial cellulose /Gelatin (BC/GA) was used as a film-forming matrix, and fluorescein isothiocyanate (FITC) and red cabbage (PCA) were used as the response signals. The addition of FITC and PCA increased the shading capacity (< 30 %) and antioxidant properties (22.8 %) of the films. WCA (82.73 ± 0.95°), WVP (1.48 × 10-11 g·cm/cm2·s·Pa) and OTR (2.42 × 10-15 cm3·cm/cm2·s·Pa) indicated that the film possessed water resistance and oxygen barrier properties. When exposed to daylight, the film underwent a color transition from purple to green as the ammonia concentration increased. In addition, the blue-green fluorescence of the films gradually increased and the detection limit was low (170 ppb). In particular, the change in film color caused by shrimp spoilage corresponded to the TVBN value. This study work provides a new strategy for controlling and monitoring food safety and has a wide range of applications in the fields of food-active packaging and smart packaging.


Asunto(s)
Gelatina , Isotiocianatos , Alimentos Marinos , Fluoresceína-5-Isotiocianato , Celulosa , Fluoresceína , Embalaje de Alimentos , Concentración de Iones de Hidrógeno , Antocianinas
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