RESUMEN
Arsenic pollution control technology in water was important to ensure environmental health and quality safety of agricultural products. Therefore, the adsorption performance of three adsorbents for chitosan, sepiolite, and Zeolitic Imidazolate Framework-8 (ZIF-8) were investigated in arsenate contaminated water. The results revealed that the adsorption capacity of ZIF-8 was higher than that of chitosan and sepiolite. The analysis of adsorption isotherm models showed that the behavior of ZIF-8 was more consistent with the Langmuir model. Furthermore, the adsorption mechanisms of three adsorbents for arsenate were investigated by Fourier-transform infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS). The analysis of FTIR showed that ZIF-8 maintained the stability of the interaction with arsenate by forming As-O chemical bonds. However, the effect of chitosan and sepiolite with arsenate was mainly physical adsorption. The analysis of XPS showed that the absorption of ZIF-8 with arsenate involved metal sites and nitrogen through the characteristic peak and the change of the binding energy. Furthermore, the impact of microplastics as a widespread coexistence pollutant in the water on adsorbent performance was investigated. The results indicated that the adsorption capacity of ZIF-8 was almost not affected by microplastics. The maximum adsorption amount of arsenate was changed from 73.45â¯mg/g to 81.89â¯mg/g. However, the maximum adsorption amount of chitosan and sepiolite decreased by 31.4â¯% and 11.6â¯%, respectively. The analysis of FTIR and XPS revealed that ZIF-8 enhances arsenate adsorption by forming N-O-As bonds in the presence of microplastics. This study provides scientific evidence for the management of arsenate pollution in water bodies, especially in complex water bodies containing microplastics.
Asunto(s)
Arseniatos , Quitosano , Microplásticos , Contaminantes Químicos del Agua , Adsorción , Arseniatos/química , Contaminantes Químicos del Agua/química , Quitosano/química , Espectroscopía Infrarroja por Transformada de Fourier , Microplásticos/química , Silicatos de Magnesio/química , Espectroscopía de Fotoelectrones , Zeolitas/química , Purificación del Agua/métodosRESUMEN
The interactions among dissolved organic matter (DOM), microplastics (MPs) and microbes influence the fate of aqueous carbon and greenhouse gas emissions. However, the related processes and mechanisms remain unclear. Here, we found that MPs determined the fate of aqueous carbon by influencing biodiversity and chemodiversity. MPs release chemical additives such as diethylhexyl phthalate (DEHP) and bisphenol A (BPA) into the aqueous phase. The microbial community, especially autotrophic bacteria such as Cyanobacteria, showed a negative correlation with the additives released from MPs. The inhibition of autotrophs promoted CO2 emissions. Meanwhile, MPs stimulated microbial metabolic pathways such as the tricarboxylic acid (TCA) cycle to accelerate the DOM biodegradation process, and then the transformed DOM presented low bioavailability, high stability, and aromaticity. Our findings highlight an urgent need for chemodiversity and biodiversity surveys to assess ecological risks from MP pollution and the impact of MPs on the carbon cycle.
Asunto(s)
Cianobacterias , Microplásticos , Plásticos , Carbono , Biodiversidad , AguaRESUMEN
OBJECTIVE: To conduct a meta-analysis of evidence from randomized controlled trails (RCTs) of different doses of intravenous immunoglobulin (IVIG) in children with severe hand, foot and mouth disease (HFMD) to provide the scientific basis for clinical practice. METHODS: A search of PubMed-Medline, CNKI, Wanfang, and VIP database (until June 30, 2017) was performed and Software RevMan5.3 was used to evaluate the effect of different doses of IVIG on HFMD in RCTs. We used random-effects models (or fixed-effects models) and generic inverse variance methods to process quantitative data, followed by a leave-one-out method for sensitivity analysis. RESULTS: From a total of 420 entries identified via searches, 8 RCTs involving 1,450 patients were included in the final analysis. The results of the meta-analysis showed that compared with conventional therapy alone, conventional therapy combined with IVIG had shorter fever clearance time, shorter rash regression time, and shorter clinical cure time. Subgroup analyses showed that the high-dose group (1 g/kg/day) had shorter fever clearance time (p < 0.05), shorter rash regression (p< 0.05), shorter remission time of neurological symptoms (p < 0.05), but longer clinical cure time (p > 0.05). CONCLUSION: The high-dose group has a better prognosis; however, the advantages and disadvantages should be carefully considered when deciding the doses in the treatment of severe HFMD.
Asunto(s)
Enfermedad de Boca, Mano y Pie/terapia , Inmunoglobulinas Intravenosas/uso terapéutico , Niño , Preescolar , Terapia Combinada , Relación Dosis-Respuesta a Droga , Exantema/terapia , Femenino , Fiebre/terapia , Humanos , Inmunoglobulinas Intravenosas/administración & dosificación , Inmunoglobulinas Intravenosas/efectos adversos , Lactante , Masculino , Ensayos Clínicos Controlados Aleatorios como Asunto , Inducción de Remisión , Índice de Severidad de la EnfermedadRESUMEN
BACKGROUND: The metastasis of breast cancer is the leading cause of death, while lung metastasis is a major clinical phenomenon in patients with invasive breast cancer. The current treatment option comprising surgery, radiation, and standard chemotherapy cannot achieve a satisfactory effect on the treatment of lung metastasis of breast cancer. In this study, we report the potential of preventing lung metastasis of invasive breast cancer using the newly developed functional vincristine plus dasatinib liposomes. METHODS: The investigations were performed on invasive breast cancer MDA-MB-231 cells in vitro and in lung metastatic model of invasive breast cancer MDA-MB-231 cells in nude mice. RESULTS: The functional drug liposomes were able to induce cell cycle arrest at G2/M phase, induce apoptosis, inhibit adhesion, migration, and invasion of breast cancer cells in vitro, and prevent lung metastasis of breast cancer in nude mice. CONCLUSION: These findings indicate a potential clinical use of functional vincristine plus dasatinib liposomes for treating metastatic breast cancer.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Dasatinib/administración & dosificación , Neoplasias Mamarias Experimentales/tratamiento farmacológico , Vincristina/administración & dosificación , Animales , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Apoptosis/efectos de los fármacos , Neoplasias de la Mama/tratamiento farmacológico , Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Dasatinib/uso terapéutico , Femenino , Humanos , Liposomas , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/secundario , Neoplasias Mamarias Experimentales/patología , Ratones Endogámicos BALB C , Ratones Desnudos , Vincristina/uso terapéuticoRESUMEN
The environmental release of nanoparticles is attracting increasing attention. Graphene oxide (GO) embedded in epoxy resin (ER) is a popular composite that has been used in various fields, but the environmental release of GO-ER composites and the effects on organisms in the environment remain unknown. The present work found that GO-ER composites in water for 2-7 days resulted in the release of 0.3-2.1% GO-ER at nanoscale (2-3 nm thickness and approximately 70-130 nm lateral length). Interestingly, pristine GO quenched 30-45% hydroxyl and 12% nitroxide free radicals, whereas this capacity was not observed for the released particles from GO-ER. At environmentally relevant concentrations (µg/L), released GO-ER particles, but not GO or ER matrix, promoted algal reproduction by 34% and chlorophyll biosynthesis by 65-127% at 96 h. Released GO-ER entered algal cells and induced a slight increase in reactive oxygen species but did not elicit notable cell structure damage. The upregulated amino acids and phenylalanine metabolism, and the downregulated fatty acid biosynthesis contributed to algal growth promoted by released GO-ER. Previous studies of pristine nanoparticles were unable to reflect the environmental effects of released nanoparticles into the environment, and our research on the exposure-toxicological continuum adds important contributions to this field.
Asunto(s)
Chlorella vulgaris , Resinas Epoxi/toxicidad , Grafito/toxicidad , Contaminantes Químicos del Agua/toxicidad , Óxidos , Especies Reactivas de OxígenoRESUMEN
This review focused on the developments in the field of molecularly imprinted polymers (MIPs) for CEC since 2009. New preparation techniques of MIP-based CEC, such as, portable microchip with macroporous monolithic imprinted microchannel, and low cross-linking MIPs based on liquid crystalline monomers, were discussed. Using selected cases rather than a comprehensive review of the entire field, our goal is to highlight the studies of the interest with an emphasis on recent work, and offers suggestions for future development in the field of imprinted materials for CEC separation.
Asunto(s)
Electrocromatografía Capilar/métodos , Impresión Molecular , Polímeros/químicaRESUMEN
Microplastics, as a type of anthropogenic pollution in aquatic ecosystems, affect the carbon cycle of organic matter. Although some studies have investigated the effects of microplastics on dissolved organic matter (DOM), the impact of alterations in the chemical properties of microplastics on refractory DOM and carbon release remains unclear. Here, we observed that microplastic treatments (e.g., polystyrene, PS) altered the composition and function of microbial community, notably increasing the abundance of microbial families involved in consuming easily degradable organic matter. During the process in which microbial community decomposed organic matter into DOM, PS underwent surface oxidation. The oxidized PS aggregated with DOM and microorganisms through electrostatic interactions and chemical bonds. Moreover, these interactions between oxidized PS and microbial community affect the utilization of organic matter, resulting in a significant decrease in CO2 emissions. Specifically, total CO2 emissions decreased by approximately 23.76 % with 0.1 mg/L PS treatment and by 44.97 % with 10 mg/L PS treatment compared to those in PS-free treatments over the entire reaction. These findings underscored the significance of the chemical properties of PS in the interactions among DOM and microorganisms, emphasizing the potential impact of PS microplastics on the carbon cycle in ecosystems.
Asunto(s)
Dióxido de Carbono , Microplásticos , Poliestirenos , Poliestirenos/química , Dióxido de Carbono/análisis , Contaminantes Químicos del Agua/análisis , Ciclo del Carbono , EcosistemaRESUMEN
Oceans absorb most excess heat from anthropogenic activities, leading to ocean warming. Moreover, microplastic pollution from anthropogenic activities is serious in marine environments and is accessible to various organisms. However, the combined effects of environmentally realistic ocean warming and microplastic pollution (OW+MP) on dominant marine species phytoplankton and related biochemical cycles are unclear. We investigated the combined effects on the dominant genera of diatoms (Chaetoceros gracilis, C. gracilis) over 100 generations. As a biological adjustment strategy, the growth rates of C. gracilis were nonsignificantly changed by OW+MP, body size decreased, and the chlorophyll a (Chl a) content and photosynthetic efficiency significantly decreased by 32.5% and 10.86%, respectively. The OW+MP condition inhibited carbon and nitrogen assimilation and sequestration capacity and allocated carbon into flexible forms of carbohydrates instead of proteins. Furthermore, the decrease in Si:C and Si:N ratios affected carbon transport to both the mesopelagic layer and deep ocean. Integrated transcriptomics and metabolomics showed that OW+MP disturbed ribosome and nitrogen metabolism. Given the rising concurrence of warming and MP pollution, the changes in metabolism suggest that the covariation in carbon, nitrogen and silicon biochemical cycles and the hidden influence on biodiversity and food web changes in the ocean should be reconsidered.
Asunto(s)
Carbono , Diatomeas , Carbono/análisis , Clorofila A , Microplásticos/metabolismo , Plásticos/metabolismo , Fitoplancton , Océanos y Mares , Nitrógeno/metabolismo , Ciclo del NitrógenoRESUMEN
Polystyrene (PS) often found in the ocean is one of the most commonly used plastic polymers in the world and can exist in different particle sizes. In particular, PS degrades relatively faster and widely accumulates at the nanoscale. Therefore, the penetration is strong and it is easy to enter the body and cause adverse effects. However, the persistence or recovery of their toxicity remains largely unclear. Here, we designed two subexperiments (exposure and recovery experiments) and investigated the persistence of the toxicity of polystyrene (PS) NPs at a wide concentration range (0.01-10 mg/L) to diatoms (Phaeodactylum tricornutum). PS-NPs significantly inhibited algal growth and clearly wrinkled the surfaces of cells, membrane permeability was significantly increased, and the steady-state state of cell redox and mitochondrial membrane potential was disturbed. However, in the recovery experiment, the increased membrane permeability was observed to persist, but the induced oxidative damage was reversible, and the absorbed NPs could be excreted. Integrated omics techniques (metabolomics and transcriptomics) revealed that PS-NPs significantly disrupts cell metabolism, including disturbances in fatty acid biosynthesis and enhanced biosynthesis of phenylalanine, tyrosine, and tryptophan. Inhibition of fatty acid, amino acid, energy and carbohydrate metabolism and disturbance of the antioxidant system contribute to the persistence of toxicity. These findings highlight the phenomena and mechanisms of the persistence of phytotoxicity and are critical to the accurate assessment of NPs.
Asunto(s)
Diatomeas , Nanopartículas , Contaminantes Químicos del Agua , Poliestirenos/metabolismo , Microplásticos/toxicidad , Nanopartículas/química , Contaminantes Químicos del Agua/toxicidad , Plásticos , Diatomeas/metabolismoRESUMEN
Microplastic pollution and heat waves, as damaging aspects of human activities, have been found to affect crop production and nitrogen (N) cycling in agroecosystems. However, the impacts of the combination of heat waves and microplastics on crop production and quality have not been analyzed. We found that heat waves or microplastics alone had slight effects on rice physiological parameters and soil microbial communities. However, under heat wave conditions, the typical low-density polyethylene (LDPE) and polylactic acid (PLA) microplastics decreased the rice yields by 32.1% and 32.9%, decreased the grain protein level by 4.5% and 2.8%, and decreased the lysine level by 91.1% and 63.6%, respectively. In the presence of heat waves, microplastics increased the allocation and assimilation of N in roots and stems but decreased those in leaves, which resulted in a reduction in photosynthesis. In soil, the concurrence of microplastics and heat waves induced the leaching of microplastics, which resulted in decreased microbial N functionality and disturbed N metabolism. In summary, heat waves amplified the disturbance induced by microplastics on the agroecosystem N cycle and therefore exacerbated the decreases in rice yield and nutrients induced by microplastics, which indicates that the environmental and food risks of microplastics deserve to be reconsidered.
Asunto(s)
Microplásticos , Oryza , Humanos , Microplásticos/toxicidad , Plásticos , Calor , Suelo , Ciclo del Nitrógeno , NitrógenoRESUMEN
Dissolved organic matter (DOM) exists widely in natural waters and plays an important role in river carbon cycles and greenhouse gas emissions through microbial interactions. However, information on DOM-microbe associations in response to environmental stress is limited. River environments are the main carriers of microplastic (MP) pollution, and global heat waves (HWs) are threatening river ecology. Here, through MP exposure and HW simulation experiments, we found that DOM molecular weight and aromaticity were closely related to initial microbial communities. Moreover, MP-derived DOM regulated microbial community abundance and diversity, influenced microorganism succession trajectories as deterministic factors, and competed with riverine DOM for microbial utilization. SimulatedHWs enhanced the MP-derived DOM competitive advantage and drove the microbial community to adopt a K-strategy for effective recalcitrant carbon utilization. Relative to single environmental stressor exposure, combined MP pollution and HWs led to a more unstable microbial network. This study addresses how MPs and HWs drive DOM-microbe interactions in rivers, contributes to an in-depth understanding of the fate of river DOM and microbial community succession processes, and narrows the knowledge gap in understanding carbon sinks in aquatic ecosystems influenced by human activities and climate change.
Asunto(s)
Microbiota , Plásticos , Humanos , Microplásticos , Materia Orgánica Disuelta , Calor , RíosRESUMEN
One of the major drawbacks of conventional molecularly imprinted polymers (MIPs) is the requirements of volatility porogenic solvent during polymerization. To overcome the default, MIP based on deep eutectic solvent (DES, a new type of green designer solvents) has been synthesized successfully. To improve the affinity of the MIP based on DES, in this work, a strategy of metallic pivot was suggested in the first time to prepare a highly selective MIP monolithic column. A cetirizine-imprinted polymer was prepared in a DES-based porogen system composed of choline chloride/ ethylene glycol (ChCl-EG) in the presence of Co(Ac)2 as metallic pivot. The resulting DES- Co2+-MIP monolith had 23.5 times higher imprinting factor than the Co2+-free MIP monolith. The characterization of polymers indicated that DES was one of the primary factor influencing the MIP morphology and pore structure. Compared with previous metal-mediated and ionic liquid-based imprinted polymers, the introduction of DES as a porogen in polymerization led to higher imprinting factor (approximately 2.9 - 17.1 times). In addition, the resulting DES-Co2+-MIP can be used as an adsorbent for extraction of cetirizine from ethanol solution with the recoveries of 97.8%. As a conclusion, the metallic pivot is a rather valuable strategy for the synthesis of DES-based MIP monolith with high selectivity.
Asunto(s)
Técnicas de Química Analítica/métodos , Metales/química , Impresión Molecular , Polímeros/síntesis química , Solventes/química , Cetirizina/química , Cetirizina/aislamiento & purificación , Etanol/química , Glicol de Etileno , Polimerizacion , Polímeros/químicaRESUMEN
Efficacy of regular chemotherapy is significantly hampered by multidrug resistance (MDR) and severe systemic toxicity. The reduced toxicity has been evidenced after administration of drug liposomes, consisting of the first generation of regular drug liposomes, the second generation of long-circulation drug liposomes, and the third generation of targeting drug liposomes. However, MDR of cancers remains as an unsolved issue. The objective of this article is to review the dual-functional drug liposomes, which demonstrate the potential in overcoming MDR. Herein, dual-functional drug liposomes are referring to the drug-containing phospholipid bilayer vesicles that possess a dual-function of providing the basic efficacy of drug and the extended effect of the drug carrier. They exhibit unique roles in treatment of resistant cancer via circumventing drug efflux caused by adenosine triphosphate binding cassette (ABC) transporters, eliminating cancer stem cells, destroying mitochondria, initiating apoptosis, regulating autophagy, destroying supply channels, utilizing microenvironment, and silencing genes of the resistant cancer. As the prospect of an estimation, dual-functional drug liposomes would exhibit more strength in their extended function, hence deserving further investigation for clinical validation.
Asunto(s)
Antineoplásicos/administración & dosificación , Portadores de Fármacos/administración & dosificación , Resistencia a Múltiples Medicamentos/efectos de los fármacos , Resistencia a Antineoplásicos/efectos de los fármacos , Liposomas/administración & dosificación , Neoplasias/tratamiento farmacológico , Transportadoras de Casetes de Unión a ATP/metabolismo , Animales , Antineoplásicos/uso terapéutico , HumanosRESUMEN
Surgery and radiotherapy cannot fully remove brain glioma; thus, chemotherapy continues to play an important role in treatment of this illness. However, because of the restriction of the blood-brain barrier (BBB) and the regeneration of glioma stem cells, post-chemotherapy relapse usually occurs. Here, we report a potential solution to these issues that involves a type of novel multifunctional vinblastine liposomes equipped with transferrin receptor binding peptide TfR-T12 and octa-arginine conjugate stearyl-R8. Studies were performed on brain glioma and glioma stem cells in vitro and were verified in brain glioma-bearing mice. The liposomes were transported across the BBB, killing brain glioma and glioma stem cells via the induction of necrosis, apoptosis and autophagy. Furthermore, we reveal the molecular mechanisms for treating brain glioma and glioma stem cells via functionalized drug lipid vesicles.
Asunto(s)
Antineoplásicos Fitogénicos/administración & dosificación , Neoplasias Encefálicas/tratamiento farmacológico , Glioma/tratamiento farmacológico , Liposomas/administración & dosificación , Células Madre Neoplásicas/efectos de los fármacos , Vinblastina/administración & dosificación , Animales , Barrera Hematoencefálica/efectos de los fármacos , Sistemas de Liberación de Medicamentos , Humanos , Liposomas/química , Ratones , Oligopéptidos/química , Receptores de Transferrina/químicaRESUMEN
Currently, chemotherapy is less efficient in controlling the continued development of breast cancer because it cannot eliminate extrinsic and intrinsic refractory cancers. In this study, mitochondria were modified by functional epirubicin liposomes to eliminate refractory cancers through initiation of an apoptosis cascade. The efficacy and mechanism of epirubicin liposomes were investigated on human breast cancer cells in vitro and in vivo using flow cytometry, confocal microscopy, high-content screening system, in vivo imaging system, and tumor inhibition in mice. Mechanistic studies revealed that the liposomes could target the mitochondria, activate the apoptotic enzymes caspase 8, 9, and 3, upregulate the proapoptotic protein Bax while downregulating the antiapoptotic protein Mcl-1, and induce the generation of reactive oxygen species (ROS) through an apoptosis cascade. In xenografted mice bearing breast cancer, the epirubicin liposomes demonstrated prolonged blood circulation, significantly increased accumulation in tumor tissue, and robust anticancer efficacy. This study demonstrated that functional epirubicin liposomes could significantly induce programmed death of refractory breast cancer by activating caspases and ROS-related apoptotic signaling pathways, in addition to the direct killing effect of the anticancer drug itself. Thus, we present a simple nanomedicine strategy to treat refractory breast cancer.
Asunto(s)
Antibióticos Antineoplásicos/farmacología , Neoplasias de la Mama/tratamiento farmacológico , Epirrubicina/farmacología , Liposomas/química , Liposomas/farmacología , Animales , Antibióticos Antineoplásicos/administración & dosificación , Apoptosis/efectos de los fármacos , Neoplasias de la Mama/patología , Caspasas/metabolismo , Epirrubicina/administración & dosificación , Femenino , Humanos , Liposomas/administración & dosificación , Células MCF-7 , Ratones , Ratones Endogámicos BALB C , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Fosfatidiletanolaminas/química , Polietilenglicoles/química , Especies Reactivas de Oxígeno/metabolismo , Distribución Tisular , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
The efficacy of chemotherapy for brain glioma is restricted by the blood-brain barrier (BBB), and surgery or radiotherapy cannot eliminate the glioma cells because of their unique location. Residual brain glioma cells can form vasculogenic mimicry (VM) channels that can cause a recurrence of brain glioma. In the present study, targeting liposomes incorporating epirubicin and celecoxib were prepared and used for the treatment of brain glioma, along with the destruction of their VM channels. Evaluations were performed on the human brain glioma U87MG cells in vitro and on intracranial brain glioma-bearing nude mice. Targeting epirubicin plus celecoxib liposomes in the circulatory blood system were able to be transported across the BBB, and accumulated in the brain glioma region. Then, the liposomes were internalized by brain glioma cells and killed glioma cells by direct cytotoxic injury and the induction of apoptosis. The induction of apoptosis was related to the activation of caspase-8- and -3-signaling pathways, the activation of the proapoptotic protein Bax, and the suppression of the antiapoptotic protein Mcl-1. The destruction of brain glioma VM channels was related to the downregulation of VM channel-forming indictors, which consisted of MMP-2, MMP-9, FAK, VE-Cad, and VEGF. The results demonstrated that the targeting epirubicin plus celecoxib liposomes were able to effectively destroy the glioma VM channels and exhibited significant efficacy in the treatment of intracranial glioma-bearing nude mice. Therefore, targeting epirubicin plus celecoxib liposomes could be a potential nanostructured formulation to treat gliomas and destroy their VM channels.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Neoplasias Encefálicas/tratamiento farmacológico , Glioma/tratamiento farmacológico , Liposomas/farmacología , Animales , Protocolos de Quimioterapia Combinada Antineoplásica/farmacocinética , Apoptosis/efectos de los fármacos , Barrera Hematoencefálica/efectos de los fármacos , Neoplasias Encefálicas/patología , Caspasa 8/metabolismo , Celecoxib/administración & dosificación , Línea Celular Tumoral , Epirrubicina/administración & dosificación , Glioma/patología , Humanos , Liposomas/química , Liposomas/farmacocinética , Masculino , Ratones Desnudos , Recurrencia Local de NeoplasiaRESUMEN
The highly infiltrative nature of brain glioma makes total surgical removal of cancerous cells virtually impossible. Regular chemotherapy plays an important role in eradicating the residual cancer cells but is ineffective in treating brain glioma due to the hindrance of drug penetration into the tumor site by the blood brain barrier (BBB) and the regeneration of cancer cells by glioma stem cells (GSCs). In this study, functional targeting daunorubicin liposomes were developed by modifying the liposomes with distearoylphosphatidylethanolamine polyethylene glycol-polyethylenimine (DSPE-PEG2000PEI600 and a lipid-glucose derivative (DSPE-PEG2000-GLU). The studies were performed in brain glioma and glioma stem cells in vitro and in brain glioma-bearing mice inoculated with the glioma stem cells. The results showed that the functional targeting daunorubicin liposomes were able to significantly transfer across the BBB and exhibited an obvious efficacy in killing glioma and glioma stem cells in mice. The action mechanisms of the functional targeting daunorubicin liposomes were related to their properties: long-duration circulation in the blood system, transport capability across the BBB, concentrated accumulation in the brain glioma site, and increased internalization by malignant cells and their mitochondria. This functional drug formulation showed anticancer efficacy through a direct cytotoxic effect and an apoptosis-inducing effect through the apoptotic signaling pathways in the cytoplasm and mitochondria of the cells. As a chemotherapy strategy for treating brain glioma, functional targeting daunorubicin liposomes have the potential to eliminate brain glioma along with glioma stem cells.
Asunto(s)
Antineoplásicos , Neoplasias Encefálicas/metabolismo , Daunorrubicina , Glioma/metabolismo , Liposomas , Animales , Antineoplásicos/química , Antineoplásicos/farmacocinética , Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Barrera Hematoencefálica/metabolismo , Línea Celular Tumoral , Daunorrubicina/química , Daunorrubicina/farmacocinética , Daunorrubicina/farmacología , Liposomas/química , Liposomas/farmacocinética , Liposomas/farmacología , Masculino , Ratones , Ratones Endogámicos ICR , Células Madre Neoplásicas/metabolismo , Ratas , Transducción de Señal/efectos de los fármacos , Distribución TisularRESUMEN
Biodegradable poly (lactic-co-glycolic acid) (PLGA), D-alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS) and/or polyethylene glycol (PEG) were combined as pharmaceutical excipient to fabricate microparticles containing sparingly soluble drug paclitaxel by spray-drying technique with successful achievement. The effect of formulation variety on particle morphology, surface composition, thermal property, drug entrapped capability, and drug release profile was investigated. The result indicated that the use of the appropriate mixtures of PLGA, TPGS and/or PEG produced paclitaxel-loaded microparticles characterised by acceptable pharmaceutical properties. Atomic force microcopy (AFM) and scanning electron microscopy (SEM) showed that the produced microparticles were spherical in shape with dimples or pores. The particle size ranged from 0.88 to 2.44 microm with narrow distribution. The combination of TPGS and PEG in the formulation resulted in a narrow particle size distribution in general although the influence of the formulation on the particle size was not significant. Differential scanning calorimetry (DSC) study implied that all those components in consideration were compatible well in the blend formulation systems. The paclitaxel entrapped in the particles existed in an amorphous or disordered-crystalline status in the matrices and was independent of the PLGA/TPGS/PEG ratio. X-ray photoelectron spectroscope (XPS) analysis revealed that after incorporation the particle's surface was dominated with PLGA due to its hydrophobic property. The formulation variety had an important impact on the drug release that was reduced with the presence of large fraction of TPGS resulting from a strong hydrophobic interaction between various matrix materials and the drug inside the particle. A zero order release could be yielded by optimising the ratio of PLGA/TPGS/PEG. The combination of PLGA/TPGS/PEG as safe pharmaceutical excipient to formulate particulate delivery system is beneficial in improving the pharmaceutical properties for further powder dosage application.
Asunto(s)
Antineoplásicos/administración & dosificación , Vitamina E/análogos & derivados , Antineoplásicos/farmacocinética , Rastreo Diferencial de Calorimetría , Fenómenos Químicos , Química Farmacéutica , Química Física , Cromatografía Líquida de Alta Presión , Composición de Medicamentos , Excipientes , Ácido Láctico , Tamaño de la Partícula , Polietilenglicoles , Ácido Poliglicólico , Copolímero de Ácido Poliláctico-Ácido Poliglicólico , Polímeros , Polvos , Solubilidad , Propiedades de SuperficieRESUMEN
Graphene oxide (GO) has been employed in various fields, and its ecological and health risks have attracted much attention. A small and inexpensive biomolecule, L-cysteine, was covalently immobilized onto GO to form L-cysteine-GO (CysGO) as a thio-functionalized nanosheet of 1.4 nm in thickness. Both the d-spacing and crystallinity of CysGO were observed to be lower than those of GO, whereas the D and G peaks remained similar to those of GO. CysGO exhibited remarkable uptake in vivo: no tissue defects, malformation, death or significant hatching delay were observed in zebrafish embryos. Significant DNA damage, decreased Na+/K+-ATPase activity and decreased mitochondrial membrane potential were not observed for CysGO. As a nonspecific activity linked to nanotoxicology, the unpaired electron spinning intensity of CysGO was approximately two orders of magnitude lower than that of GO. Oxygen microsensor analysis showed that the hypoxic and normoxic environments resulting from the presence of GO and CysGO envelopment, respectively, contributed to the difference in biocompatibility. CysGO also protected embryos from arsenic poisoning. Thus, CysGO has the advantageous properties of GO, exhibits excellent biocompatibility, acts as a breathable coating and antidote, and is suitable for various applications.
Asunto(s)
Materiales Biocompatibles/química , Materiales Biocompatibles Revestidos/química , Cisteína/química , Grafito/química , Óxidos/química , Animales , Arsénico/toxicidad , Supervivencia Celular , Cristalización , Medios de Cultivo/química , Daño del ADN , Espectroscopía de Resonancia por Spin del Electrón , Embrión no Mamífero , Radicales Libres/química , Potencial de la Membrana Mitocondrial , Microscopía de Fuerza Atómica , Nanotecnología , Oxígeno/química , Especies Reactivas de Oxígeno/química , Propiedades de Superficie , Pez CebraRESUMEN
The objectives of the present study were to develop functional targeting epirubicin liposomes for transferring drugs across the blood-brain barrier (BBB), treating glioblastoma, and disabling neovascularization. The studies were performed on glioblastoma cells in vitro and on glioblastoma-bearing mice. The results showed that the constructed liposomes had a high encapsulation efficiency for drugs (>95%), suitable particle size (109 nm), and less leakage in the blood component-containing system; were significantly able to be transported across the BBB; and exhibited efficacies in killing glioblastoma cells and in destroying glioblastoma neovasculature in vitro and in glioblastoma-bearing mice. The action mechanisms of functional targeting epirubicin liposomes correlated with the following features: the long circulation in the blood system, the ability to be transported across the BBB via glucose transporter-1, and the targeting effects on glioblastoma cells and on the endothelial cells of the glioblastoma neovasculature via the integrin ß3 receptor. In conclusion, functional targeting epirubicin liposomes could be used as a potential therapy for treating brain glioblastoma and disabling neovascularization in brain glioblastomas.