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1.
PLoS One ; 11(7): e0158493, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27411088

RESUMEN

Industrial oil spills into aquatic environments can have catastrophic environmental effects. First responders to oil spills along the coast of the Gulf of Mexico in the southern United States have used spunbond nylon fabric bags and fences to separate spilled oil and oil waste from contaminated water. Low area mass density spunbond nylon is capable of sorbing more than 16 times its mass in low viscosity crude oil and more than 26 times its mass in higher viscosity gear lube oil. Nylon bags separated more than 95% of gear lube oil contaminate from a 4.5% oil-in-water emulsion. Field testing of spunbond nylon fences by oil spill first responders has demonstrated the ability of this material to contain the oily contaminate while allowing water to flow through. We hypothesize that the effectiveness of nylon as an oil filter is due to the fact that it is both more oleophilic and more hydrophilic than other commonly used oil separation materials. The nylon traps oil droplets within the fabric or on the surface, while water droplets are free to flow through the fabric to the water on the opposite side of the fabric.


Asunto(s)
Caprolactama/análogos & derivados , Restauración y Remediación Ambiental/instrumentación , Restauración y Remediación Ambiental/legislación & jurisprudencia , Filtración/instrumentación , Filtración/métodos , Aceites/química , Contaminación por Petróleo , Petróleo/metabolismo , Polímeros/química , Contaminantes Químicos del Agua/química , Caprolactama/química , Emulsiones/química , Restauración y Remediación Ambiental/métodos , Golfo de México , Interacciones Hidrofóbicas e Hidrofílicas , Textiles , Agua/química , Contaminación del Agua
2.
Int J Nanomedicine ; 11: 2163-77, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27274241

RESUMEN

Tumor-associated macrophages (TAMs) are critically important in the context of solid tumor progression. Counterintuitively, these host immune cells can often support tumor cells along the path from primary tumor to metastatic colonization and growth. Thus, the ability to transform protumor TAMs into antitumor, immune-reactive macrophages would have significant therapeutic potential. However, in order to achieve these effects, two major hurdles would need to be overcome: development of a methodology to specifically target macrophages and increased knowledge of the optimal targets for cell-signaling modulation. This study addresses both of these obstacles and furthers the development of a therapeutic agent based on this strategy. Using ex vivo macrophages in culture, the efficacy of mannosylated nanoparticles to deliver small interfering RNA specifically to TAMs and modify signaling pathways is characterized. Then, selective small interfering RNA delivery is tested for the ability to inhibit gene targets within the canonical or alternative nuclear factor-kappaB pathways and result in antitumor phenotypes. Results confirm that the mannosylated nanoparticle approach can be used to modulate signaling within macrophages. We also identify appropriate gene targets in critical regulatory pathways. These findings represent an important advance toward the development of a novel cancer therapy that would minimize side effects because of the targeted nature of the intervention and that has rapid translational potential.


Asunto(s)
Macrófagos/inmunología , FN-kappa B/metabolismo , Nanomedicina/métodos , Nanopartículas/administración & dosificación , ARN Interferente Pequeño/administración & dosificación , Animales , Células de la Médula Ósea/citología , Línea Celular Tumoral , Quimiocina CXCL9/genética , Quimiocina CXCL9/inmunología , Quimiocina CXCL9/metabolismo , Femenino , Glicosilación , Lípidos , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Ratones Noqueados , Ratones Transgénicos , Inhibidor NF-kappaB alfa/genética , Inhibidor NF-kappaB alfa/metabolismo , FN-kappa B/genética , Neoplasias/metabolismo , Neoplasias Ováricas/patología , ARN Interferente Pequeño/genética , Transducción de Señal/genética , Factor de Necrosis Tumoral alfa/farmacología
3.
CBE Life Sci Educ ; 14(2)2015.
Artículo en Inglés | MEDLINE | ID: mdl-25917385

RESUMEN

Concept mapping was developed as a method of displaying and organizing hierarchical knowledge structures. Using the new, multidimensional presentation software Prezi, we have developed a new teaching technique designed to engage higher-level skills in the cognitive domain. This tool, synthesis mapping, is a natural evolution of concept mapping, which utilizes embedding to layer information within concepts. Prezi's zooming user interface lets the author of the presentation use both depth as well as distance to show connections between data, ideas, and concepts. Students in the class Biology of Cancer created synthesis maps to illustrate their knowledge of tumorigenesis. Students used multiple organizational schemes to build their maps. We present an analysis of student work, placing special emphasis on organization within student maps and how the organization of knowledge structures in student maps can reveal strengths and weaknesses in student understanding or instruction. We also provide a discussion of best practices for instructors who would like to implement synthesis mapping in their classrooms.


Asunto(s)
Evaluación Educacional/métodos , Conocimiento , Modelos Educacionales , Modelos Psicológicos , Programas Informáticos , Estudiantes , Humanos , Modelos Lineales
4.
Nanoscale ; 7(2): 500-10, 2015 Jan 14.
Artículo en Inglés | MEDLINE | ID: mdl-25408159

RESUMEN

Tumor associated macrophages (TAMs) can modify the tumor microenvironment to create a pro-tumor niche. Manipulation of the TAM phenotype is a novel, potential therapeutic approach to engage anti-cancer immunity. siRNA is a molecular tool for knockdown of specific mRNAs that is tunable in both strength and duration. The use of siRNA to reprogram TAMs to adopt an immunogenic, anti-tumor phenotype is an attractive alternative to ablation of this cell population. One current difficulty with this approach is that TAMs are difficult to specifically target and transfect. We report here successful utilization of novel mannosylated polymer nanoparticles (MnNP) that are capable of escaping the endosomal compartment to deliver siRNA to TAMs in vitro and in vivo. Transfection with MnNP-siRNA complexes did not significantly decrease TAM cell membrane integrity in culture, nor did it create adverse kidney or liver function in mice, even at repeated doses of 5 mg kg(-1). Furthermore, MnNP effectively delivers labeled nucleotides to TAMs in mice with primary mammary tumors. We also confirmed TAM targeting in the solid tumors disseminated throughout the peritoneum of ovarian tumor bearing mice following injection of fluorescently labeled MnNP-nucleotide complexes into the peritoneum. Finally, we show enhanced uptake of MnNP in lung metastasis associated macrophages compared to untargeted particles when using an intubation delivery method. In summary, we have shown that MnNP specifically and effectively deliver siRNA to TAMs in vivo.


Asunto(s)
Materiales Biocompatibles/química , Portadores de Fármacos/química , Endosomas/metabolismo , Manosa/química , Nanopartículas/química , ARN Interferente Pequeño/metabolismo , Animales , Materiales Biocompatibles/metabolismo , Línea Celular Tumoral , Supervivencia Celular , Técnicas de Cocultivo , Femenino , Colorantes Fluorescentes/química , Pulmón/metabolismo , Pulmón/patología , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/secundario , Neoplasias Pulmonares/terapia , Macrófagos/citología , Macrófagos/metabolismo , Macrófagos/trasplante , Neoplasias Mamarias Animales/patología , Neoplasias Mamarias Animales/secundario , Neoplasias Mamarias Animales/terapia , Manosa/metabolismo , Ratones , Ratones Endogámicos C57BL , Microscopía Fluorescente , Nanopartículas/metabolismo , Neoplasias Ováricas/metabolismo , Neoplasias Ováricas/patología , Polímeros/química , ARN Interferente Pequeño/química , ARN Interferente Pequeño/uso terapéutico , Trasplante Homólogo , Microambiente Tumoral
5.
Artículo en Inglés | MEDLINE | ID: mdl-21834059

RESUMEN

An estimated 16 million people in the United States have coronary artery disease (CAD), and approximately 325,000 people die annually from cardiac arrest. About two-thirds of unexpected cardiac deaths occur without prior recognition of cardiac disease. A vast majority of these deaths are attributable to the rupture of 'vulnerable atherosclerotic plaques'. Clinically, plaque vulnerability is typically assessed through imaging techniques, and ruptured plaques leading to acute myocardial infarction are treated through angioplasty or stenting. Despite significant advances, it is clear that current imaging methods are insufficiently capable for elucidating plaque composition--which is a key determinant of vulnerability. Further, the exciting improvement in the treatment of CAD afforded by stenting procedures has been buffered by significant undesirable host-implant effects, including restenosis and late thrombosis. Nanotechnology has led to some potential solutions to these problems by yielding constructs that interface with plaque cellular components at an unprecedented size scale. By leveraging the innate ability of macrophages to phagocytose nanoparticles, contrast agents can now be targeted to plaque inflammatory activity. Improvements in nano-patterning procedures have now led to increased ability to regenerate tissue isotropy directly on stents, enabling gradual regeneration of normal, physiologic vascular structures. Advancements in immunoassay technologies promise lower costs for biomarker measurements, and in the near future, may enable the addition of routine blood testing to the clinician's toolbox--decreasing the costs of atherosclerosis-related medical care. These are merely three examples among many stories of how nanotechnology continues to promise advances in the diagnosis and treatment of vulnerable atherosclerotic plaques.


Asunto(s)
Nanomedicina , Nanoestructuras/uso terapéutico , Placa Aterosclerótica , Enfermedad de la Arteria Coronaria/diagnóstico , Enfermedad de la Arteria Coronaria/terapia , Humanos , Placa Aterosclerótica/diagnóstico , Placa Aterosclerótica/terapia
6.
J Nanobiotechnology ; 9: 7, 2011 Feb 27.
Artículo en Inglés | MEDLINE | ID: mdl-21352596

RESUMEN

BACKGROUND: Drug and contrast agent delivery systems that achieve controlled release in the presence of enzymatic activity are becoming increasingly important, as enzymatic activity is a hallmark of a wide array of diseases, including cancer and atherosclerosis. Here, we have synthesized clusters of ultrasmall superparamagnetic iron oxides (USPIOs) that sense enzymatic activity for applications in magnetic resonance imaging (MRI). To achieve this goal, we utilize amphiphilic poly(propylene sulfide)-bl-poly(ethylene glycol) (PPS-b-PEG) copolymers, which are known to have excellent properties for smart delivery of drug and siRNA. RESULTS: Monodisperse PPS polymers were synthesized by anionic ring opening polymerization of propylene sulfide, and were sequentially reacted with commercially available heterobifunctional PEG reagents and then ssDNA sequences to fashion biofunctional PPS-bl-PEG copolymers. They were then combined with hydrophobic 12 nm USPIO cores in the thin-film hydration method to produce ssDNA-displaying USPIO micelles. Micelle populations displaying complementary ssDNA sequences were mixed to induce crosslinking of the USPIO micelles. By design, these crosslinking sequences contained an EcoRV cleavage site. Treatment of the clusters with EcoRV results in a loss of R2 negative contrast in the system. Further, the USPIO clusters demonstrate temperature sensitivity as evidenced by their reversible dispersion at ~75°C and re-clustering following return to room temperature. CONCLUSIONS: This work demonstrates proof of concept of an enzymatically-actuatable and thermoresponsive system for dynamic biosensing applications. The platform exhibits controlled release of nanoparticles leading to changes in magnetic relaxation, enabling detection of enzymatic activity. Further, the presented functionalization scheme extends the scope of potential applications for PPS-b-PEG. Combined with previous findings using this polymer platform that demonstrate controlled drug release in oxidative environments, smart theranostic applications combining drug delivery with imaging of platform localization are within reach. The modular design of these USPIO nanoclusters enables future development of platforms for imaging and drug delivery targeted towards proteolytic activity in tumors and in advanced atherosclerotic plaques.


Asunto(s)
Preparaciones de Acción Retardada/síntesis química , Dextranos/química , Nanopartículas de Magnetita/química , Polietilenglicoles/síntesis química , Sulfuros/síntesis química , Reactivos de Enlaces Cruzados/química , Micelas , Polietilenglicoles/química
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