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1.
Pak J Pharm Sci ; 34(6(Special)): 2455-2459, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-35039259

RESUMEN

To explore the effect of R-CHOP regimen of pegylated liposomal doxorubicin (PLD) on elderly stage Ⅲ-Ⅳ diffuses large B-cell lymphoma (DLBCL). A retrospective analysis was conducted on the treatment information 80 elderly cases of stage III-IV DLBCL admitted to our hospital from April 2017 to April 2020. According to treatment methods, they were divided into experimental groups (40 cases, using R-CHOP with PLD) and controls group (40 cases, using the traditional R-CHOP regimen). We compared the treatment effect, survival rate, cardiotoxicity and adverse reactions of the patients. (1) The short-term degree of effectiveness treatment in the experimental group was 85%, which was not significantly different from 80% in other patients (p>0.05). (2) 2-year OS or PFS of experimental group were better more (p<0.01) and the treatment advantage of the experimental group increased with time. (3) Incidence of neutropenia and alopecia in experimental group was lower more (p<0.05). (4) Cardiotoxicity indexes of experimental group were lower (p<0.05). The PLD-containing R-CHOP regimen can improve the long-term inventory level elderly cases of stage III-IV DLBCL, reduce the incidence of grade IV neutropenia and alopecia, alleviate the cardiotoxicity caused by chemotherapy, and have better safety.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Doxorrubicina/análogos & derivados , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Factores de Edad , Anciano , Anciano de 80 o más Años , Alopecia/inducido químicamente , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Cardiotoxicidad , Ciclofosfamida/efectos adversos , Ciclofosfamida/uso terapéutico , Progresión de la Enfermedad , Doxorrubicina/efectos adversos , Doxorrubicina/uso terapéutico , Femenino , Cardiopatías/inducido químicamente , Humanos , Linfoma de Células B Grandes Difuso/mortalidad , Linfoma de Células B Grandes Difuso/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Neutropenia/inducido químicamente , Polietilenglicoles/efectos adversos , Polietilenglicoles/uso terapéutico , Prednisona/efectos adversos , Prednisona/uso terapéutico , Supervivencia sin Progresión , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Rituximab/efectos adversos , Rituximab/uso terapéutico , Factores de Tiempo , Vincristina/efectos adversos , Vincristina/uso terapéutico
2.
Biomacromolecules ; 21(12): 5269-5281, 2020 12 14.
Artículo en Inglés | MEDLINE | ID: mdl-33226784

RESUMEN

The amphiphilic cationic polymers that mimic antimicrobial peptides have received increasing attention due to their excellent antibacterial activity. However, the relationship between the structure of cationic polymers and its antibacterial effect remains unclear. In our current work, a series of PEG blocked amphiphilic cationic polymers composed of hydrophobic alkyl-modified and quaternary ammonium salt (QAS) moieties have been prepared. The structure-antibacterial activity relationship of these cationic polymers was investigated against E. coli and S. aureus, including PEGylation, random structure, molecular weights, and the content and lengths of the hydrophobic alkyl side chains. The results indicated that PEGylated random amphiphilic cationic copolymer (mPB35/T57) showed stronger antibacterial activity and better biocompatibility than the random copolymer without PEG (PB33/T56). Furthermore, mPB35/T57 with appropriate mole fraction of alkyl side chains (falkyl = 0.38), degree of polymerization (DP = 92), and four-carbon hydrophobic alkyl moieties was found to have the optimal structure that revealed the best antibacterial activities against both E. coli (MIC = 8 µg/mL, selectivity > 250) and S. aureus (MIC = 4 µg/mL, selectivity > 500). More importantly, mPB35/T57 could effectively eradicate E. coli biofilms by killing the bacteria embedded in the biofilms. Therefore, the structure of mPB35/T57 provided valuable information for improving the antibacterial activity of cationic polymers.


Asunto(s)
Polímeros , Staphylococcus aureus , Antibacterianos/farmacología , Antibiosis , Cationes , Escherichia coli , Pruebas de Sensibilidad Microbiana
3.
J Mater Sci Mater Med ; 30(3): 37, 2019 Mar 06.
Artículo en Inglés | MEDLINE | ID: mdl-30840152

RESUMEN

In this work, the setting process of reduced graphene (RGO)/carbon nanotubes (CNTs) reinforced calcium phosphate cement (CPC) were conducted in a microwave environment. The introduction of microwave can increase the reaction temperature, speed up the vibration of water molecules and eliminate bubbles from the interface between RGO, CNTs and the substrate. Comparing with CPC without microwave treatment, the final setting time of composites after microwave treatment are almost a half, the flexural strength and the compressive strength are increased by 19.86% and 21.68% respectively, which are 17.38 MPa and 104.52 MPa. Meanwhile, the CPC composites remain the excellent bioactivity.


Asunto(s)
Cementos para Huesos/química , Fosfatos de Calcio/química , Grafito/química , Nanotubos de Carbono/química , Huesos/patología , Fuerza Compresiva , Humanos , Inflamación , Ensayo de Materiales , Microscopía Electrónica de Rastreo , Microondas , Presión , Estrés Mecánico , Temperatura
4.
J Agric Food Chem ; 72(29): 16530-16540, 2024 Jul 24.
Artículo en Inglés | MEDLINE | ID: mdl-39001851

RESUMEN

Brassica napus is currently the principal field crop for producing materials for primary, secondary and tertiary industries. B. napus shoots at stem elongation stage are rich in anthocyanins, vitamin C and mineral elements such as selenium, calcium and zinc, and represent a new type of green vegetable. However, the high crude fiber (CF) content of B. napus shoots affects their taste, and few studies have focused on the quality traits of these vegetables. In this study, we investigated five traits related to the CF components, including neutral detergent fiber (NDF), acid detergent fiber (ADF), acid detergent lignin (ADL), hemicellulose (Hem) and cellulose (Cel), of B. napus shoots. Whole-genome resequencing at a depth of ∼20× was utilized to genotype an association panel of 202 diverse accessions, which resulted in the identification of 6,093,649 single nucleotide polymorphisms (SNPs) and 996,252 indels, respectively. A genome-wide association study (GWAS) was performed for the five CF-related traits based on the phenotypic data observed in four environments. A total of 1,285 significant SNPs were detected at the threshold of -log10 (p) = 5.16, and 97 significant association regions were obtained. In addition, seven candidate genes located on chromosomes A2 (one gene), A8 (three genes), A9 (two genes) and C9 (one gene) related to CF traits were identified, and ten lines containing low CF contents were selected as excellent germplasm resources for breeding. Our results contributed new insights into the genetic basis of CF traits and suggested germplasm resources for the quality improvement of B. napus shoots.


Asunto(s)
Brassica napus , Estudio de Asociación del Genoma Completo , Tallos de la Planta , Polimorfismo de Nucleótido Simple , Brassica napus/genética , Brassica napus/crecimiento & desarrollo , Brassica napus/metabolismo , Brassica napus/química , Tallos de la Planta/genética , Tallos de la Planta/química , Tallos de la Planta/crecimiento & desarrollo , Tallos de la Planta/metabolismo , Brotes de la Planta/crecimiento & desarrollo , Brotes de la Planta/genética , Brotes de la Planta/química , Brotes de la Planta/metabolismo , Genotipo , Fibras de la Dieta/metabolismo , Fibras de la Dieta/análisis , Fenotipo , Celulosa/metabolismo , Lignina/metabolismo , Polisacáridos/metabolismo , Polisacáridos/química , Sitios de Carácter Cuantitativo
5.
Acta Biomater ; 171: 428-439, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37716478

RESUMEN

The non-fouling condition, bacteria-free environment and suitable moisture at wound site are crucial for chronic wound healing. However, it remains highly meaningful yet challenging to develop wound dressings that can simultaneously achieve these desirable functions. In this work, a kind of multifunctional Janus polyurethane sponge (Janus-PU) was designed and fabricated by coating near-infrared (NIR)-responsive and superhydrophobic nanoparticles (F-ZnO@Ag NPs) on one surface of sponge. The nano-functionalized outer layer can endow Janus-PU with superhydrophobic antifouling property for preventing bacterial colonization and broad-spectrum antibacterial activity due to the presence of Ag NPs. Especially, the synergistic combination of asymmetric structure and strong NIR photothermal effect can impart Janus-PU with NIR-controlled unidirectional exudate removal, thus achieving an optimal wetting environment for wound healing. The mice full-thickness skin acute wounds treated with Janus-PU under NIR irradiation showed superior anti-infection and healing effect compared to the commercial dressings. Significantly, the treatment using Janus-PU with NIR irradiation can accelerate the recovery of methicillin-resistant Staphylococcus aureus (MRSA)-infected diabetic chronic wounds due to the synergistic effect of antibiofouling, antibacterial and exudate-managing. The Janus-PU as a promising multifunctional dressing can prevent bacterial invasion and create an appropriate environment for wound healing, providing an effective solution for intractable wounds and infections. STATEMENT OF SIGNIFICANCE: The development of advanced wound dressings to ensure non-fouling condition, bacteria-free environment and suitable moisture is crucial for chronic wound healing. However, it remains a considerable challenge to simultaneously integrate antibiofouling, antibacterial and exudate-managing properties into a single dressing. In this work, we developed a kind of multifunctional Janus polyurethane sponge (Janus-PU) by a single-sided superhydrophobic modification strategy, which can simultaneously achieve superhydrophobic antifouling property, effective broad-spectrum antibacterial and near-infrared controlled exudate removal. The Janus-PU designed herein can not only create an optimal environment for accelerated wound healing, but also avoid frequent dressing replacement, thus providing an ideal material system for intractable wounds and infections.


Asunto(s)
Staphylococcus aureus Resistente a Meticilina , Poliuretanos , Ratones , Animales , Poliuretanos/farmacología , Poliuretanos/química , Cicatrización de Heridas , Bacterias , Antibacterianos/farmacología , Antibacterianos/química , Vendajes/microbiología
6.
Nat Commun ; 14(1): 7393, 2023 11 15.
Artículo en Inglés | MEDLINE | ID: mdl-37968364

RESUMEN

The underlying mechanism of chronic hepatitis B virus (HBV) functional cure by interferon (IFN), especially in patients with low HBsAg and/or young ages, is still unresolved due to the lack of surrogate models. Here, we generate a type I interferon receptor humanized mouse (huIFNAR mouse) through a CRISPR/Cas9-based knock-in strategy. Then, we demonstrate that human IFN stimulates gene expression profiles in huIFNAR peripheral blood mononuclear cells (PBMCs) are similar to those in human PBMCs, supporting the representativeness of this mouse model for functionally analyzing human IFN in vivo. Next, we reveal the tissue-specific gene expression atlas across multiple organs in response to human IFN treatment; this pattern has not been reported in healthy humans in vivo. Finally, by using the AAV-HBV model, we test the antiviral effects of human interferon. Fifteen weeks of human PEG-IFNα2 treatment significantly reduces HBsAg and HBeAg and even achieves HBsAg seroconversion. We observe that activation of intrahepatic monocytes and effector memory CD8 T cells by human interferon may be critical for HBsAg suppression. Our huIFNAR mouse can authentically respond to human interferon stimulation, providing a platform to study interferon function in vivo. PEG-IFNα2 treatment successfully suppresses intrahepatic HBV replication and achieves HBsAg seroconversion.


Asunto(s)
Hepatitis B Crónica , Hepatitis B , Humanos , Ratones , Animales , Virus de la Hepatitis B/fisiología , Antígenos de Superficie de la Hepatitis B , Antivirales/farmacología , Antivirales/uso terapéutico , Interferón-alfa/farmacología , Interferón-alfa/uso terapéutico , Leucocitos Mononucleares/metabolismo , Proteínas Recombinantes/farmacología , Polietilenglicoles/farmacología , ADN Viral , Resultado del Tratamiento
7.
Chem Res Toxicol ; 25(6): 1265-70, 2012 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-22587431

RESUMEN

As graphene becomes one of the most exciting candidates for multifunctional biomedical applications, contact between eyes and graphene-based materials is inevitable. On the other hand, eyes, as a special organ in the human body, have unique advantages to be used for testing new biomedical research and development, such as drug delivery. Intraocular biocompatible studies on graphene-related materials are thus essential. Here, we report our recent studies on intraocular biocompatibility and cytotoxicity of graphene oxide (GO) both in vitro and in vivo. The successful preparation of GO nanosheets was confirmed using atomic force microscopy, contact angle analyzer, Fourier transform infrared spectroscopy, and Raman spectroscopy. The influence of GO on human retinal pigment epithelium (RPE) cells in terms of the cell morphology, viability, membrane integrity, and apoptosis was investigated using various techniques, including optical micrography, cell counting kit-8 (CCK-8) assay, lactate dehydrogenase (LDH) assay, and apoptosis assay. The addition of GO had little influence on cell morphology, but the change was visible after long-time culturing. RPE cells showed higher than 60% cell viability by CCK-8 assay in GO solutions and less than 8% LDH release, although a small amount of apoptosis (1.5%) was observed. In vitro results suggested good biocompatibility of GO to RPE cells with slight adverse influence, on the cell viability and morphology in long-time periods, along with aggregation of GO. Thus, some further studies are needed to clarify the cytotoxicity mechanism of GO. GO intravitreally injected eyes showed few changes in eyeball appearance, intraocular pressure (IOP), eyesight, and histological photos. Our results suggested that GO did not cause any significant toxicity to the cell growth and proliferation. Intravitreal injection of GO into rabbits' eyes did not lead to much change in the eyeball appearance, IOP, electroretinogram, and histological examination.


Asunto(s)
Ojo/efectos de los fármacos , Ojo/fisiopatología , Grafito/toxicidad , Óxidos/toxicidad , Animales , Apoptosis/efectos de los fármacos , Materiales Biocompatibles , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Electrorretinografía , Ojo/patología , Grafito/administración & dosificación , Grafito/química , Humanos , Óxidos/administración & dosificación , Óxidos/química , Conejos , Relación Estructura-Actividad
8.
Sci Total Environ ; 839: 156318, 2022 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-35636551

RESUMEN

The occurrence of microplastics (MPs, <5 mm) in drinking water has aroused extensive concerns, whereas our understanding of their presence in groundwater, a major source of drinking water, is still limited. The present study investigated the occurrence of microplastics in groundwater sampled from five sites in Jiaodong Peninsula, China. The abundance, type, and size of MPs in the groundwater samples were determined by Laser Direct Infrared following a well-established and quality-controlled analytical route. Notably, MPs were detected in groundwater across all five sampling sites, with high abundances ranging from 87 to 6832 particles/L and an average abundance of 2103 particles/L. The variation of the abundance of MPs was correlated to the distances between sampling sites and anthropogenic activities, which suggested significant impacts of aboveground industry and agriculture on the abundance of MPs in groundwater. Polyethylene terephthalate (PET) and polyurethane (PU) were the dominant polymer types detected in all groundwater samples. The MPs with a size smaller than 100 µm were found to account for >90% of the total MPs detected in four sampling sites, which was likely associated with their migratory routes through surface water runoff and infiltration into the groundwater settings. The results of this study suggest the importance of counting small MPs when determining their abundances in groundwater or their abundances would be considerably underestimated. The present study for the first time demonstrated the occurrence of MPs in groundwater in China, which improves our understanding of the MPs distribution and raises concerns about groundwater safety in terms of MPs pollution.


Asunto(s)
Agua Potable , Agua Subterránea , Contaminantes Químicos del Agua , China , Monitoreo del Ambiente/métodos , Microplásticos , Plásticos , Contaminantes Químicos del Agua/análisis
9.
J Drug Target ; 30(7): 767-776, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-35379059

RESUMEN

The nano-drug delivery system activated by the tumour microenvironment (TME) can effectively treat tumours with low toxicity. Based on a high level of reductive GSH in TME and the different coordination properties of Fe ions, this project intended to prepare a GSH-activated cascade catalytic nanoreactor for breast cancer treatment using Fe3+/Fe2+ as the molecular switch. In this study, the glucose oxidase (GOx) loaded iron alginate nano hydrogel (FeAlg/GOx) was prepared by the simple one-step titration method. Results showed that FeAlg/GOx could remain stable during in vivo circulation to avoid hypoglycaemia. When it reached the targeted tumour site, reductive GSH can reduce Fe3+ to Fe2+. Thereafter, FeAlg/GOx nanogel was broken and GOx was released to consume the essential nutrient glucose (Glu) to achieve tumour starvation therapy. Next, the substrate H2O2 generated by the reaction between GOx and Glu can be catalysed by Fe2+ to produce highly cytotoxic •OH in situ, which could further kill tumour cells. The in vivo pharmacodynamics results demonstrated that compared with the control group (V/V0 = 8.36 ± 1.73), FeAlg/GOx group showed the most significant anti-tumour effect with V/V0 of 3.08 ± 1.06. In conclusion, this "inactivated" FeAlg/GOx nanogel can be converted into "activated" therapeutic substances in situ to achieve starvation-chemodynamic combined treatment for breast cancer.


Asunto(s)
Neoplasias de la Mama , Neoplasias , Neoplasias de la Mama/tratamiento farmacológico , Línea Celular Tumoral , Femenino , Glucosa , Glucosa Oxidasa , Humanos , Peróxido de Hidrógeno/química , Nanogeles , Nanotecnología , Neoplasias/tratamiento farmacológico , Microambiente Tumoral
10.
Oxid Med Cell Longev ; 2022: 7135125, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35300175

RESUMEN

Transdermal drug delivery system is a preferable choice to overcome the low bioavailability of oral medication. Elastic liposomes have shown great effectiveness for percutaneous transport of melatonin (MLT). In this study, the elastic liposomes loaded with MLT were prepared using thin-film dispersion method and optimized through the central composite design (CCD) approach. The physicochemical properties and skin permeation against UV-induced skin photoaging efficacy of the developed MLT-ELs were assessed. The average size of the MLT-ELs was about 49 nm with a spherical shape and high encapsulation efficiency (73.91%) and drug loading (9.92%). The results of FTIR, DSC, and XRD revealed that the chemical structure of MLT was not changed after prepared elastic liposomes, and the drug was successfully encapsulated in the elastic liposome membrane material. In vitro skin permeation evaluation showed that the cumulative penetration of elastic liposomes was 1.5 times higher than that of conventional liposomes, highlighting that the elastic liposomes more easily penetrated into the body. The photoaging experiment results indicated that topical MLT-EL treatment ameliorated the skin elasticity, enhanced the skin hydration level, and preserved the integrity of dermal collagen and elastic fibers. It could be concluded that the elastic liposomes might serve as a promising platform for the transdermal delivery of melatonin.


Asunto(s)
Liposomas/química , Melatonina/administración & dosificación , Envejecimiento de la Piel/efectos de los fármacos , Animales , Elasticidad , Femenino , Melatonina/farmacocinética , Melatonina/farmacología , Ratones , Piel/efectos de los fármacos , Piel/metabolismo
11.
J Colloid Interface Sci ; 628(Pt B): 79-94, 2022 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-35985065

RESUMEN

Hydrogel-based drug delivery holds great promise in topical tumor treatment. However, the simple construction of multifunctional therapeutic hydrogels under physiological conditions is still a huge challenge. Herein, for the first time, a multifunctional hyaluronan/MnO2 nanocomposite (HHM) hydrogel with injectable and self-healing capabilities was constructed under physiological conditions through innovative in situ mineralization-triggered Mn-hydrazide coordination crosslinking. The hydrogel formed from Mn2+ and hydrazided hyaluronan under optimized conditions exhibited a high elastic modulus >1 kPa, injectability, self-healing function, stimuli-responsiveness and catalase-like activity. In vitro and in vivo biological experiments demonstrated that our HHM hydrogel could not only efficiently relieve hypoxia by in situ catalytic decomposition of endogenous H2O2 into O2 but also achieve synergistic photodynamic/photothermal therapy of 4T1 breast cancer in a mouse tumor model. This study presented a novel mineralization-driven metal-hydrazide coordination crosslinking approach and developed a multifunctional therapeutic platform for O2-enhanced efficient topical dual-phototherapy of breast cancer.


Asunto(s)
Ácido Hialurónico , Hipoxia Tumoral , Ratones , Animales , Nanogeles , Catalasa , Compuestos de Manganeso/farmacología , Hidrazinas/farmacología , Peróxido de Hidrógeno , Línea Celular Tumoral , Óxidos , Fototerapia , Hidrogeles/farmacología
12.
Drug Deliv Transl Res ; 12(3): 603-614, 2022 03.
Artículo en Inglés | MEDLINE | ID: mdl-33860450

RESUMEN

The objective of this study was to fabricate a novel drug delivery system using Soluplus® (polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer) and glycyrrhizic acid to improve solubility, bioavailability, and anti-hyperuricemic activity of aloe emodin (AE). The AE-loaded mixed micelles (AE-M) were prepared by thin-film hydration method. The optimal AE-M contained small-sized (30.13 ± 1.34 nm) particles with high encapsulation efficiency (m/m, %) of 90.3 ± 1.08%. The release rate of AE increased in the micellar formulation than that of free AE in the four media (DDW, pH 7.0; phosphate buffer solution, pH 7.4; phosphate buffer solution, pH 6.8; and hydrochloric acid aqueous solution, pH 1.2). In comparison to free AE, the pharmacokinetic study of AE-M showed that its relative oral bioavailability increased by 3.09 times, indicating that mixed micelles may promote gastrointestinal absorption. More importantly, AE-M effectively reduced uric acid level by inhibiting xanthine oxidase (XOD) activity in model rats. The degree of ankle swelling, serum levels of interleukin (IL)-1, and IL-6-related inflammatory factors levels all decreased in the gouty arthritis model established via monosodium urate (MSU) crystals. Taken together, the AE-M demonstrated the potential to improve the bioavailability, anti-hyperuricemic activity, and anti-inflammation of AE.


Asunto(s)
Ácido Glicirrínico , Micelas , Administración Oral , Animales , Antraquinonas , Disponibilidad Biológica , Fosfatos , Polietilenglicoles/química , Polivinilos , Ratas
13.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(4): 1065-1070, 2021 Aug.
Artículo en Zh | MEDLINE | ID: mdl-34362483

RESUMEN

OBJECTIVE: To investigate the expression of peptidylarginine deiminase 4 (PADI4) during the process of differentiation into granulocyte of NB4 cells induced by all-trans-retinoic acid (ATRA) and whether PADI4 is involved in the inflammatory cytokines expression. METHODS: Granulocyte differentiation model of NB4 cells induced by ATRA was established. The cell morphology changes were observed by Wright-Giemsa staining. The expression of cell differentiation marker CD11b was analyzed by flow cytometry. The mRNA and protein expression of PADI4 was detected by RT-PCR and Western blot, respectively. The expression of tumor necrosis factor (TNF) α and interleukin (IL) 1ß was analyzed by ELISA, and also examined with the knockdown of PADI4 expression by siRNA. RESULTS: After NB4 cells induced by ATRA, the cytoplasm increased and the ratio of nuclear to cytoplasmic was reduced. Nuclear dented, and rod-shaped nucleus, lobulated phenomenon increased (P<0.05). Flow cytometry analysis results showed that the cell surface molecule CD11b expression increased (P<0.01). RT-PCR and Western blot showed the expression of PADI4 increased at both transcriptional and translational levels during the process of the differentiation. ELISA showed TNF-α and IL-1ß secretion increased in differentiated macrophages, while they could be inhibited by PADI4-specific siRNA. CONCLUSION: During the differentiation into granulocyte of NB4 cells induced by ATRA, PADI4 expression increased. Furthermore, PADI4 appeared to play a critical role in inflammatory cytokines secretion.


Asunto(s)
Diferenciación Celular , Citocinas/metabolismo , Leucemia Promielocítica Aguda , Arginina Deiminasa Proteína-Tipo 4/metabolismo , Línea Celular Tumoral , Granulocitos , Humanos , Tretinoina/farmacología
14.
Macromol Biosci ; 20(7): e2000143, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-32401412

RESUMEN

Owing to the biodegradability and good biocompatibility polycarbonates show the versatile class of applications in biomedical fields. While their poor functional ability seriously limited the development of functional polycarbonates. Herein, a new Br-containing cyclic carbonate (MTC-Br) and a polycarbonate atom transfer radical polymerization (ATRP) macro-initiator (PEG-PMTC-Br) is synthesized. Then, by initiating the side-chain ATRP of 2-(dimethyl amino)ethyl methacrylate (DMAEMA) on PEG-PMTC-Br, a series of comb-like amphiphilic cationic polycarbonates, PEG-b-(PMTC-g-PDMAEMA) (GMDMs), with different lengths of cationic branches are successfully prepared. All these poly(ethylene glycol)-b-(poly((5-methyl-2-oxo-1,3-dioxane-5-yl) methyl 2-bromo-2-methylpropanoate/1,3-dioxane-2-one)-g-poly(2-dimethyl aminoethyl methacrylate) (GMDMs) self-assembled nanoparticles (NPs) (≈180 nm, +40 mV) can well bind siRNA to form GMDM/siRNA NPs. The gene silence efficiency of GMDM/siRNA high to 80%, which is even higher than the commercial transfection reagent lipo2000 (76%). But GMDM/siRNA shows lower cell uptake than lipo2000. So, the high gene silence ability of GMDM/siRNA NPs can be attributed to the strong intracellular siRNA trafficking capacity. Therefore, GMDM NPs are potential siRNA vectors and the successful preparation of comb-like polycarbonates also provides a facile way for diverse side-chain functional polycarbonates, expanding the application of polycarbonates.


Asunto(s)
Técnicas de Transferencia de Gen , Cemento de Policarboxilato/química , ARN Interferente Pequeño/metabolismo , Tensoactivos/química , Bromuros/química , Cationes , Endocitosis , Células Hep G2 , Humanos , Metacrilatos/síntesis química , Metacrilatos/química , Nanopartículas/química , Nylons/síntesis química , Nylons/química , Tamaño de la Partícula , Cemento de Policarboxilato/síntesis química , Espectroscopía de Protones por Resonancia Magnética , Espectroscopía Infrarroja por Transformada de Fourier , Electricidad Estática
15.
ACS Appl Mater Interfaces ; 12(32): 35873-35881, 2020 Aug 12.
Artículo en Inglés | MEDLINE | ID: mdl-32667184

RESUMEN

Cell membrane imaging by predesigned molecular and supramolecular photoluminescence probes is of great importance in understanding the nano-biointeractions for potential applications in cellular tracking, drug delivery, cancer diagnosis, and treatment. Herein, we report an effective strategy for cell membrane imaging in both living cell and tissue levels on the basis of a multifunctional nanocage (MOC-16) integrating one-/two-photon active phosphorescence, high charges, balanced hydrophobicity/lipophilicity, and proton sensitivity attributes. The intrinsic optical characters, including strong one-/two-photon excitation and pH-dependent red emission, make MOC-16 powerful optical probes for membrane imaging in living cell and tissue levels under both visible and near-infrared irradiations. Meanwhile, the highly positive charges of +28 endow MOC-16 with adequate water solubility and deprotonation ability while still maintaining its hydrophobicity, thus enabling balanced hydrophobic-lipophilic interactions at the nano-biointerface to facilitate a pH-dependent membrane absorption within the biological pH range of 5.3-7.4. However, the low-charged RuL3 metalloligand or polyethylene glycol (PEG)-modified MOC-16PEG with less hydrophobicity cannot offer enough nano-biointeractions for cell membrane tracking. These findings advance the fundamental understanding of nano-biointerface interactions of MOCs with cell membranes and provide further guidance in their biological applications.


Asunto(s)
Colorantes Fluorescentes/química , Nanopartículas del Metal/química , Imagen Óptica/métodos , Imagen Individual de Molécula/métodos , Membrana Celular/metabolismo , Membrana Celular/ultraestructura , Permeabilidad de la Membrana Celular , Células HeLa , Humanos , Concentración de Iones de Hidrógeno , Interacciones Hidrofóbicas e Hidrofílicas , Rayos Infrarrojos , Microscopía de Fluorescencia por Excitación Multifotónica , Compuestos Organometálicos , Paladio/química , Fotones , Polietilenglicoles/química , Rutenio/química
16.
J Mater Chem B ; 7(38): 5789-5796, 2019 10 14.
Artículo en Inglés | MEDLINE | ID: mdl-31483429

RESUMEN

Near-infrared (NIR) irradiation responsive drug delivery systems have many advantages, which have attracted extensive interest from researchers. In this study, a NIR-triggered drug release system was established by grafting upper critical solution temperature (UCST) polymers on the surface of hollow mesoporous silica nanoparticles (HMSNs) followed by treatment with the photothermal conversion agent indocyanine green (ICG). The as-prepared UCST polymers showed the clearing temperature of 45 °C, which were advantageous to serve as gatekeepers in the physiological environment (37 °C). Under NIR irradiation, the temperature of the solution was elevated above the clearing point due to the presence of ICG; consequently, the collapsed UCST polymer chains became more hydrophilic; this resulted in the exposure of the mesoporous channels of the HMSNs and achievement of a burst drug release. Moreover, this NIR-responsive delivery system showed good biocompatibility and high anticancer efficiency towards the MCF-7 cancer cells upon exposure to NIR irradiation. In addition, a synergistic effect of thermal and chemo treatment has been achieved by the application of NIR irradiation since cancer cells are more vulnerable to high temperatures than normal cells.


Asunto(s)
Verde de Indocianina/metabolismo , Rayos Infrarrojos , Nanopartículas/química , Polímeros/química , Dióxido de Silicio/química , Antineoplásicos/química , Antineoplásicos/metabolismo , Antineoplásicos/farmacología , Materiales Biocompatibles/química , Supervivencia Celular/efectos de los fármacos , Doxorrubicina/química , Doxorrubicina/metabolismo , Doxorrubicina/farmacología , Portadores de Fármacos/química , Liberación de Fármacos , Humanos , Interacciones Hidrofóbicas e Hidrofílicas , Verde de Indocianina/química , Verde de Indocianina/farmacología , Células MCF-7 , Microscopía Confocal , Nanopartículas/toxicidad , Porosidad , Propiedades de Superficie , Temperatura
17.
Colloids Surf B Biointerfaces ; 181: 602-611, 2019 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-31202131

RESUMEN

The combination of chemotherapy and photothermal therapy is acknowledged as one of the most promising approaches in cancer treatment. Targeted delivery and controlled drug release are two important factors for combined chemo-photothermal therapy. In this study, a multifunctional nanoplatform based on gold nanorod (GNR) decorated with folate-conjugated poly(ethylene glycol)-b-poly(L-γ-glutamylhydrazine) (FEGGH) containing disulfide linker and dihydroxyphenyl groups was developed for targeted combined chemo-photothermal therapy of breast cancer. FEGGH was synthesized by ring-opening polymerization of γ-benzyl-l-glutamate-N-carboxyanhydride using folate/cystamine-heterobifunctionalized poly(ethylene glycol) as an initiator, following by hydrazinolysis and carbodiimide reactions. FEGGH was decorated onto GNR through Au-catechol bonds. Chemotherapeutic drug doxorubicin (DOX) was loaded onto the nanoplatform through pH-sensitive hydrazone linkage, obtaining final product FEGGHDOX-GNR. The DOX-loaded nanoplatform displayed excellent photostability and reduction/pH dual-responsive drug release behavior. Cytological studies demonstrated the effective internalization of FEGGHDOX-GNR into MCF-7 cells via folate-mediated endocytosis and additive therapeutic effect of combined photothermal-chemotherapy. These results indicate that our nanoplatform may be a promising strategy for targeted combined chemo-photothermal therapy of breast cancer.


Asunto(s)
Antibióticos Antineoplásicos/farmacología , Neoplasias de la Mama/terapia , Doxorrubicina/farmacología , Oro/química , Nanotubos/química , Péptidos/química , Polietilenglicoles/química , Apoptosis/efectos de los fármacos , Neoplasias de la Mama/patología , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Quimioterapia Combinada , Femenino , Oro/farmacología , Humanos , Células MCF-7 , Estructura Molecular , Tamaño de la Partícula , Fototerapia , Relación Estructura-Actividad , Propiedades de Superficie , Células Tumorales Cultivadas
18.
J Mater Chem B ; 7(39): 6024-6034, 2019 10 09.
Artículo en Inglés | MEDLINE | ID: mdl-31545333

RESUMEN

A versatile coating strategy, which is suitable for the anti-corrosion and anti-fouling modification of chemically distinct substrates, is crucial in many industries. The immobilization of zwitterionic polymers onto the surface has been proven to be an excellent approach for the improvement of antibiofouling potency. However, the anti-corrosion property has not always been considered simultaneously. Herein, a layer-by-layer (LBL) zwitterionic surface modification strategy was proposed: the surface was first coated with a polydopamine (PDA) layer for anti-corrosion; then, by self-assembling a monolayer of 3-aminopropyl triethoxysilane (APTES), the anti-corrosion ability was further enhanced and the efficiency of grafting was improved; thereafter, by immobilizing the zwitterionic polysulfobetaine (PSB) polymer brush layer, the surface could effectively repel biofouling. The surface chemical composition and morphology characterization was performed by using attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy, scanning electron microscopy (SEM), atomic force microscopy (AFM), and water contact angle measurements, demonstrating that the modification was stepwise introduced onto the surface. The thickness of coating was observed and measured by SEM cross-sectional analysis. In vitro studies revealed that the PSB coated surfaces dramatically reduced the adhesion of bovine serum albumin (BSA), bovine plasma fibrinogen (Fg), bovine γ-globulin (γ-GL), the mixture of these proteins, fibroblasts, E. coli and S. aureus with superior cytocompatibility and hemocompatibility. Moreover, the electrochemical impedance spectroscopy and acidic corrosion studies indicated that an excellent and durable anti-corrosion property was established successfully on the surfaces of stainless steel, cotton textile and wood plates, confirming the feasibility of the LBL surface modification strategy. Significantly, this LBL surface chemistry may be widely applied for the modification of other materials, such as biosensors, biomedical implants and/or devices, and marine equipment.


Asunto(s)
Incrustaciones Biológicas/prevención & control , Indoles/química , Indoles/farmacología , Polímeros/química , Polímeros/farmacología , Células 3T3-L1 , Animales , Adhesión Bacteriana/efectos de los fármacos , Corrosión , Escherichia coli/efectos de los fármacos , Hemólisis/efectos de los fármacos , Ensayo de Materiales , Ratones , Propilaminas/química , Silanos/química , Staphylococcus aureus/efectos de los fármacos , Propiedades de Superficie
19.
J Hazard Mater ; 380: 120893, 2019 12 15.
Artículo en Inglés | MEDLINE | ID: mdl-31325691

RESUMEN

Selective enriching low content of radionuclides from radioactive wastewater is a critical issue for environmentally benign utilization of nuclear power. Inspired by the tolerance mechanism of plants to radionuclides, we developed a pH-triggered ultraselective coordinative adsorption (CA) membrane. The as-prepared CA membrane featured the advantages of both coordinative adsorption and membrane separation, including ultrahigh selectivity coefficient of 1242, large capacity (80 L m-2) and short mass transfer distance. The adsorption isotherms of Th4+ on the CA membrane were well described by the Freundlich model (R2 > 0.99), and the adsorption kinetics have a good fitting by using the pseudo-second-order kinetic model (R2 > 0.99). In a continuous separation under gravity, the CA membrane was able to selectively enrich the low content of Th4+ (0.05 mmol L-1) in the presence of 700 folds (35 mmol L-1) of co-existing ions (Na+, Mg2+, K+, Ca2+, Sr2+, Cs+ and Ba2+). The exceptional extraction efficiency to Th4+ was 100%, superior to that (3.7%) of all co-existing ions. Notably, the Th4+ enriched on the CA membrane was facilely eluted by diluted HNO3 (0.1 mol L-1). The Th4+ in the eluents was enriched by up to 54 folds. The eluted CA membrane was further reused for selective enrichment of Th4+, which showed no obvious loss of selectivity and enrichment capability. Our strategy might open up a new strategy for realizing ultraselective and recyclable enrichment of low content of irradiation contaminants from wastewater.


Asunto(s)
Adaptación Fisiológica , Fenómenos Fisiológicos de las Plantas , Torio/metabolismo , Membranas Artificiales , Taninos/metabolismo , Torio/análisis
20.
Mater Sci Eng C Mater Biol Appl ; 76: 313-318, 2017 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-28482533

RESUMEN

Though much progress in utilizing tissue engineering technology to investigate tumor development in vitro has been made, the effective management of human melanoma is still a challenge in clinic due to lack of suitable 3D culture systems. In this study, we prepared a poly(γ-benzyl-l-glutamate)/poly(lactic acid) (PBLG/PLA) nanofiber membrane by electrospinning and demonstrated its suitability as a matrix for 3D culture of melanoma cells in vitro. The electrospun PBLG/PLA nanofiber membrane displayed a smooth and uniform fibrous morphology and had a desirable water contact angle of 79.3±0.6°. The average diameter of PBLG/PLA nanofibers was 320.3±95.1nm that was less than that (516.2±163.3nm) of pure PLA nanofibers. The addition of PBLG into PLA decreased the cold crystallization peak of PLA fibers from 93 to 75°C. The in vitro biocompatibility of PBLG/PLA nanofiber membrane was evaluated with B16F10 cells using PLA nanofiber membrane as control. It was found that, compared to PLA nanofiber membrane, PBLG/PLA nanofiber membrane could better support cell viability and proliferation, as indicated by MTT assay and live-dead staining. SEM results revealed that PBLG/PLA rather than PLA nanofiber membrane promoted the generation of tumoroid-like structures. These findings clearly demonstrated that the electrospun PBLG/PLA nanofiber membrane could mimick the extracellular matrix of melanoma microenvironment and be a promising platform for 3D cell culture.


Asunto(s)
Nanofibras , Ácido Glutámico , Humanos , Melanoma , Membranas , Poliésteres , Ácido Poliglutámico/análogos & derivados , Ingeniería de Tejidos
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