RESUMEN
Ferroptosis therapy, which uses ferroptosis inducers to produce lethal lipid peroxides and induce tumor cell death, is considered a promising cancer treatment strategy. However, challenges remain regarding how to increase the accumulation of reactive oxygen species (ROS) in the tumor microenvironment (TME) to enhance antitumor efficacy. In this study, a hyaluronic acid (HA) encapsulated hollow mesoporous manganese dioxide (H-MnO2) with double-shell nanostructure is designed to contain iron coordinated cyanine near-infrared dye IR783 (IR783-Fe) for synergistic ferroptosis photodynamic therapy against tumors. The nano photosensitizer IR783-Fe@MnO2-HA, in which HA actively targets the CD44 receptor, subsequently dissociates and releases Fe3+ and IR783 in acidic TME. First, Fe3+ consumes glutathione to produce Fe2+, which promotes the Fenton reaction in cells to produce hydroxyl free radicals (·OH) and induce ferroptosis of tumor cells. In addition, MnO2 catalyzes the production of O2 from H2O2 and enhances the production of singlet oxygen (1O2) by IR783 under laser irradiation, thus increasing the production and accumulation of ROS to provide photodynamic therapy. The highly biocompatible IR783-Fe@MnO2-HA nano-photosensitizers have exhibited tumor-targeting ability and efficient tumor inhibition in vivo due to the synergistic effect of photodynamic and ferroptosis antitumor therapies.
Asunto(s)
Ferroptosis , Hierro , Compuestos de Manganeso , Fotoquimioterapia , Fármacos Fotosensibilizantes , Fotoquimioterapia/métodos , Ferroptosis/efectos de los fármacos , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/química , Hierro/química , Humanos , Animales , Compuestos de Manganeso/química , Compuestos de Manganeso/farmacología , Línea Celular Tumoral , Óxidos/química , Especies Reactivas de Oxígeno/metabolismo , Ratones , Nanoestructuras/química , Ácido Hialurónico/química , Indoles/química , Indoles/farmacologíaRESUMEN
Liposome modification by targeting ligands has been used to mediate specific interactions and drug delivery to target cells. In this study, a new peptide ligand, CP7, was found to be able to effectively bind to FGFR1 through reverse molecular docking and could cooperate with VEGFR3 to achieve targeting of A549 cells. CP7 was modified on the surface of the liposome to construct a targeted and safe nanovehicle for the delivery of a therapeutic gene, Mcl-1 siRNA. Due to the specific binding between CP7 and A549 cells, siRNA-loaded liposome-PEG-CP7 showed increased cellular uptake in vitro, resulting in significant apoptosis of tumor cells through silencing of the Mcl-1 gene, which is associated with apoptosis and angiogenesis. This gene delivery system also showed significantly better antitumor activity in tumor-bearing mice in vivo. All of these suggested that siRNA-loaded liposome-PEG-CP7 could be a promising gene drug delivery system with good bioavailability and minimal side effects for treatment.
Asunto(s)
Liposomas , Neoplasias Pulmonares , Animales , Línea Celular Tumoral , Sistemas de Liberación de Medicamentos/métodos , Liposomas/química , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/terapia , Ratones , Simulación del Acoplamiento Molecular , Proteína 1 de la Secuencia de Leucemia de Células Mieloides , Péptidos/química , Péptidos/genética , ARN Interferente Pequeño/metabolismoRESUMEN
In the crystal structure of the title hydrate, C(8)H(4)Br(2)O(4)·H(2)O, O-Hâ¯O hydrogen bonds link the mol-ecules into a two-dimensional network parallel to (10-2). The acid groups of the main mol-ecule and the water mol-ecule are all involved in the supra-molecular structure. The dihedral angles between the benzene ring and the acid groups are 37.8â (4) and 36.4â (5)°, while the dihedral angle between the acid groups is 10.9â (4)°.
RESUMEN
BACKGROUND: Particle-based drug delivery systems (DDSs) have a demonstrated value for drug discovery and development. However, some problems remain to be solved, such as limited stimuli, visual-monitoring. AIM: To develop an intelligent multicolor DDSs with both near-infrared (NIR) controlled release and macroscopic color changes. MATERIALS AND METHODS: Microparticles comprising GO/pNIPAM/PEGDA composite hydrogel inverse opal scaffolds, with dextran and calcium alginate hydrogel were synthesized using SCCBs as the template. The morphology of microparticle was observed under scanning electron microscopy, and FITC-dextran-derived green fluorescence images were determined using a confocal laser scanning microscope. During the drug release, FITC-dextran-derived green fluorescence images were captured using fluorescent inverted microscope. The relationship between the power of NIR and the drug release rate was obtained using the change in optical density (OD) values. Finally, the amount of drug released could be estimated quantitatively used the structural color or the reflection peak position. RESULTS: A fixed concentration 8% (v/v) of PEGDA and 4mg/mL of GO was chosen as the optimal concentration based on the balance between appropriate volume shrinkage and structure color. The FITC-dextran was uniformly encapsulated in the particles by using 0.2 wt% sodium alginate. The microcarriers shrank because of the photothermal response and the intrinsic fluorescence intensity of FITC-dextran in the microparticles gradually decreased at the same time, indicating drug release. With an increasing duration of NIR irradiation, the microparticles gradually shrank, the reflection peak shifted toward blue and the structural color changed from red to orange, yellow, green, cyan, and blue successively. The drug release quantity can be predicted by the structural color of microparticles. CONCLUSION: The multicolor microparticles have great potential in drug delivery systems because of its vivid reporting color, excellent photothermal effect, and the good stimuli responsivity.
Asunto(s)
Portadores de Fármacos/química , Microesferas , Resinas Acrílicas/química , Alginatos/química , Color , Dextranos/química , Liberación de Fármacos , Fluoresceína-5-Isotiocianato/análogos & derivados , Fluoresceína-5-Isotiocianato/química , Hidrogeles/química , Fenómenos Ópticos , Polietilenglicoles/químicaRESUMEN
The interaction between the chiral drug of propranolol (PPL) and alpha1-acid glycoprotein (AGP, orosomucoid) has been first studied by fluorescence spectrophotometry. The fluorescence intensity of PPL increased due to the addition of AGP into PPL. The equation of Scatchard was employed to calculate the association constant and binding site number of the two enantiomers with AGP. The association constant is 2.62 x 10(5)M-1 for R-PPL and 8.57 x 10(5)M-1 for S-PPL and the binding site number is 0.41 for R-PPL and 1.17 for S-PPL at 17 degrees C respectively. The method of thermodynamics was applied to determine the binding type of S-PPL with AGP. The results suggested that the binding type is mainly van der waals force or hydrogen bond. At last the effect of three metal cations on the association constant and the binding site number of S-PPL with AGP was examined.
Asunto(s)
Orosomucoide/química , Propranolol/química , Espectrometría de Fluorescencia , EstereoisomerismoRESUMEN
A novel type of suspension array for multiplex detection of heavy metal ions with photonic crystal hydrogel microspheres was reported. The photonic crystal hydrogel microspheres have close-packed photonic crystal particles as their encoding units and ssDNA-functionalized hydrogel as the sensing units. The developed microspheres were successfully applied in multiplex detection of heavy metal ions.
Asunto(s)
Metales Pesados/análisis , Benzotiazoles , Cationes/análisis , Cristalización , Sondas de ADN , ADN de Cadena Simple , Diaminas , Colorantes Fluorescentes , Humanos , Hidrogeles , Metales Pesados/toxicidad , Microesferas , Fenómenos Ópticos , Compuestos Orgánicos , Quinolinas , Contaminantes Químicos del Agua/análisis , Contaminantes Químicos del Agua/toxicidadRESUMEN
BACKGROUND: The appearance of antibodies to platelets in the blood is an important cause of immune thrombocytopenia (ITP), and platelet glycoprotein (GP)-specific antibody detection may be helpful to diagnose this condition. METHODS: Photonic crystal microspheres with different distinct reflection spectra were coated with anti-GPIIb, -GPIIIa, -GPIb and -GPIX monoclonal antibodies (MoAbs) to create a photonic crystal-encoded suspension array (PCSA). Fluorescein isothiocyanate-labelled goat anti-human IgG was added to detect human IgG simultaneously. The detection results were analysed by fluorescence microscopy. Parallel MoAb immobilization of platelet antigen (MAIPA) was used as a reference test. Both methods were used to analyse 63 clinical samples including serum from 32 ITP patients and 31 healthy humans. RESULTS: The PCSA showed greater sensitivity than MAIPA in detecting anti-GPIIb (75.0% vs 31.1%) and GPIIIa (84.4% vs 40.6%) antibodies and similar sensitivity as MAIPA in detecting anti-GPIb (37.5% vs 34.4%) and GPIX (50.0% vs 40.8%) antibodies. The MAIPA and PCSA tests had similar specificity. The PCSA detected higher dilutions of serum containing anti-GPIIIa antibody or anti-GPIIb antibody than did MAIPA. The entire testing process was controlled within 3.5h. CONCLUSIONS: The PCSA assay described has comparable or better sensitivity and specificity compared to the MAIPA and is more rapid.
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Anticuerpos Monoclonales/sangre , Anticuerpos Monoclonales/inmunología , Plaquetas/inmunología , Fotones , Púrpura Trombocitopénica Idiopática/diagnóstico , Púrpura Trombocitopénica Idiopática/inmunología , Humanos , Microesferas , Púrpura Trombocitopénica Idiopática/patologíaRESUMEN
Hydrogel colloidal crystal composite materials have a demonstrated value in responsive photonic crystals (PhCs) via controllable stimuli. Although they have been successfully exploited to generate a gradient of color distribution, the soft hydrogels have limitations in terms of stability and storage caused by dependence on environment. Here, we present a practical strategy to fabricate free-standing PhC films with a stable gradient of structural colors using binary polymer networks. A colloidal crystal hydrogel film was prepared for this purpose, with continuously varying photonic band gaps corresponding to the gradient of the press. Then, a second polymer network was used to lock the inside non-close-packed PhC structures and color distribution of the hydrogel film. It was demonstrated that our strategy could bring about a solution to the angle-dependent structural colors of the PhC films by coating the surface with special microstructures.
RESUMEN
A novel colorimetric logic system based on the aptamer-cross-linked colloidal crystal hydrogel (CCH) was developed. With the input stimuli of Hg(2+) and Ag(+), the CCH displayed shrinking response and colour change corresponding to the logical "OR" and "AND" gate. The visualization of the logic output signals is realized.
RESUMEN
Particle-based delivery systems have a demonstrated value for drug discovery and development. Here, we report a new type of particle-based delivery system that has controllable release and is self-monitoring. The particles were composed of poly(N-isopropylacrylamide) (pNIPAM) hydrogel with an inverse opal structure. The presence of macropores in the particles provides channels for active drug loading and release from the materials.
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Resinas Acrílicas/química , Medios de Contraste/síntesis química , Preparaciones de Acción Retardada/síntesis química , Monitoreo de Drogas/métodos , Nanocápsulas/química , Difusión , Microscopía Fluorescente/métodos , Nanocápsulas/administración & dosificación , Nanocápsulas/ultraestructura , Tamaño de la Partícula , Nanomedicina Teranóstica/métodosRESUMEN
A simple, rapid, field-portable colorimetric method for the detection of entecavir was proposed based on the color change caused by the aggregation of silver nanoparticles. Neutralization of the electrostatic repulsion from each silver nanoparticle resulted in the aggregation of AgNPs and a consequent color change of AgNPs from yellow to wine-red, which provided a platform for rapid and field-portable colorimetric detection of entecavir. The concentration of entecavir could be determined with naked eye or UV-vis spectrometer. The proposed method can be used to detect entecavir in human urine with a detection limit of 1.51µg mL(-1), within 25min by naked eye observation without the aid of any advanced instrument or complex pretreatment. Results from UV-vis spectra showed that the absorption ratio was linear with the concentration of entecavir in the range of 5.04-25.2µg mL(-1) and 1.01-5.04µg mL(-1) with linear coefficients of 0.9907 and 0.9955, respectively. The selectivity of AgNPs detection system for entecavir is excellent comparing with other ions and analytes. Due to its rapid, visible color changes, and excellent selectivity, the AgNPs synthesized in this study are suitable to be applied to on-site screening of entecavir in human urine.
Asunto(s)
Antivirales/orina , Guanina/análogos & derivados , Nanopartículas/química , Plata/química , Ácido Cítrico/química , Colorimetría/economía , Colorimetría/métodos , Guanina/orina , Humanos , Límite de Detección , Nanopartículas/ultraestructura , Espectrofotometría Ultravioleta/economía , Espectrofotometría Ultravioleta/métodosRESUMEN
A novel suspension array, which possesses the joint advantages of photonic crystal encoded technology, bioresponsive hydrogels, and photonic crystal sensors with capability of full multiplexing label-free detection is developed.
Asunto(s)
Cápsulas/química , Ensayos Analíticos de Alto Rendimiento/métodos , Fenómenos Ópticos , Hidrogeles/química , Mercurio/química , Microscopía Electrónica de Rastreo , Nanopartículas/química , Dióxido de Silicio/química , Análisis Espectral , SuspensionesRESUMEN
Barcode particles have a demonstrated value for multiplexed bioassays in clinical diagnostics, drug discovery, and so on. Attempts to develop this technology are focusing on the generation of novel particles with a large number of identifications to increase the throughput of the assays. Here we report a new type of barcode particles with quantum dot (QD)-photonic crystal (PC) joint spectrum encoding. These barcode particles are simply prepared by in-situ polymerization of CdTe QDs-contained acrylamide pre-gel in the colloidal photonic crystal beads (PCBs). By encapsulating different wavelength-and-intensity QDs into the PCBs with various-reflection spectra, thousands of available barcode particles could be obtained. Moreover, by employing magnetic nanoparticles into the PCBs, the achieved barcode particles could be conferred a function of controllable movement under magnetic field. This feature could significantly increase the sensitivity and simplify the processing of the bioassays.
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Bioensayo/instrumentación , Materiales Biocompatibles Revestidos/síntesis química , Nanotecnología/instrumentación , Análisis de Secuencia por Matrices de Oligonucleótidos/instrumentación , Puntos Cuánticos , Diseño de Equipo , Análisis de Falla de Equipo , Luz , MicroesferasRESUMEN
Solid phase extraction (SPE) has emerged as the widely used technique for sample preparation in the analytical process. Recent research trends of SPE are toward developing novel adsorbents to enrich the analytes simply and effectively. In this study, we proposed the poly-3,4-ethylenedioxythiophene (PEDOT) nanoclusters as the SPE adsorbent. During the application, only a small amount of PEDOT nanoclusters was needed and placed in a pipet tip with glass wool on either side. Without complex preparation, the target analytes could be directly extracted from the sample onto the extraction material and eluted in this lab-in-a-pipet-tip system. The efficiency of this approach was demonstrated by detecting 20 kinds of sulfonamides (SAs) in honey with ultra-performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS). All the analytes were detected by multiple reaction monitoring (MRM) mode. The established method was extensively validated by determining the linearity (R(2)≥0.991), average recovery (88.4-105.0%) and precision (relative standard deviation ≤9.60%). Low detection limits (0.5-4 µg kg(-1)), wide linearity (10-250 µg kg(-1)) and short sample pretreatment time (20 min) were achieved under the optimized conditions. The absolute recoveries of the SAs at high level ranged from 71.1% to 91.4%. Due to its simplicity, selectivity and sensitivity, our new method has potential applications in quantitative analysis of the target compounds in complex samples.
Asunto(s)
Compuestos Bicíclicos Heterocíclicos con Puentes/química , Nanoestructuras/química , Polímeros/química , Extracción en Fase Sólida/métodos , Adsorción , Cromatografía Líquida de Alta Presión/métodos , Formiatos/química , Miel/análisis , Concentración de Iones de Hidrógeno , Límite de Detección , Nanoestructuras/ultraestructura , Reproducibilidad de los Resultados , Extracción en Fase Sólida/instrumentación , Sulfonamidas/análisis , Sulfonamidas/aislamiento & purificación , Espectrometría de Masas en Tándem/métodosRESUMEN
An angle-independent photonic crystal (PhC) colorimetric sensor was developed by using a stimuli-response hydrogel to replicate the template arrays of isotropic photonic crystal beads (PCBs) for the detection of Hg(2+).
Asunto(s)
Colorimetría/métodos , Hidrogeles/química , Mercurio/análisis , Cationes Bivalentes/análisis , Cristalización , Agua Potable/análisis , Lagos/análisis , Límite de Detección , FotonesRESUMEN
We have developed a robust method for the visual detection of heavy metal ions (such as Hg(2+) and Pb(2+)) by using aptamer-functionalized colloidal photonic crystal hydrogel (CPCH) films. The CPCHs were derived from a colloidal crystal array of monodisperse silica nanoparticles, which were polymerized within the polyacrylamide hydrogel. The heavy metal ion-responsive aptamers were then cross-linked in the hydrogel network. During detection, the specific binding of heavy metal ions and cross-linked single-stranded aptamers in the hydrogel network caused the hydrogel to shrink, which was detected as a corresponding blue shift in the Bragg diffraction peak position of the CPCHs. The shift value could be used to estimate, quantitatively, the amount of the target ion. It was demonstrated that our CPCH aptasensor could screen a wide concentration range of heavy metal ions with high selectivity and reversibility. In addition, these aptasensors could be rehydrated from dried gels for storage and aptamer protection. It is anticipated that our technology may also be used in the screening of a broad range of metal ions in food, drugs and the environment.