Glutathione-Triggered catalytic response of Copper-Iron mixed oxide Nanoparticles. Leveraging tumor microenvironment conditions for chemodynamic therapy

Heterogeneous catalysis has emerged as a promising alternative for the development of new cancer therapies. In addition, regarding the tumor microenvironment as a reactor with very specific chemical features has provided a new perspective in the search for catalytic nanoarchitectures with specific action against chemical species playing a key role in tumor metabolism. One of these species is glutathione (GSH), whose depletion is the cornerstone of emerging strategies in oncology, since this metabolite plays a pivotal regulatory role as antioxidant agent, dampening the harmful effects of intracellular reactive oxidative species (ROS). Herein, we present copper-iron oxide spinel nanoparticles that exhibit a versatile and selective catalytic response to reduce GSH levels while generating ROS in a cascade reaction. We demonstrate a clear correlation between GSH depletion and apoptotic cell death in tumor cells in the presence of the copper-iron nanocatalyst. Furthermore, we also provide a novel analytical protocol, alternative to state-of-the-art commercial kits, to accurately monitoring the concentration of GSH intracellular levels in both tumor and healthy cells. We observe a selective action of the nanoparticles, with lower toxicity in healthy cell lines, whose intrinsic GSH levels are lower, and intense apoptosis in tumor cells accompanied by a fast reduction of GSH levels

Desarrollo de catalizadores que mimetizan el comportamiento enzimático regulatorio del metabolismo en células tumorales

Las enzimas juegan un papel importante en el correcto funcionamiento del metabolismo humano, ya que actúan como catalizadores de reacciones bioquímicas. Presentan alta actividad catalítica y elevada especificidad. Al mismo tiempo ofrecen inconvenientes que dificultan su aplicación práctica tales como su elevado coste de preparación y purificación, una baja estabilidad y una disminución de su actividad catalítica en condiciones ambientales. En los últimos años, se ha incrementado el interés en evaluar la capacidad de distintos nanomateriales inorgánicos como catalizadores enzimáticos artificiales. Estos nanomateriales inorgánicos conocidos como nanozimas, presentan una serie de ventajas potenciales sobre sus análogos naturales que incluyen: i) una estructura robusta y con menor tendencia a la desactivación en condiciones de reacción exigentes como las que se pueden encontrar en entornos tumorales y ii) la posibilidad de síntesis y escalado a partir de precursores de menos coste y relativamente más abundantes. Por ello, estas nanozimas han pasado a ser consideradas como alternativas de gran interés en el campo de la Nanomedicina, ya sea como biosensores o como parte del tratamiento de enfermedades como el cáncer.En este Trabajo de Fin de Máster se ha llevado a cabo el estudio sistemático de oxidación de glucosa, uno de los metabolitos con mayor incidencia en el desarrollo de células cancerosas. Para ello se ha seleccionado una enzima natural como la glucosa oxidasa (GOx) que cataliza la oxidación de la β-D-glucosa a δ-gluconolactona y un catalizador enzimático artificial de dióxido de titanio (P25-TiO2) formado en un 70% por anatasa y un 30% de rutilo. Asimismo, se ha evaluado el catalizador híbrido combinando ambos sistemas. Los principales resultados han demostrado una mayor actividad catalítica de los híbridos GOx-P25 tras irradiación a 365 y 405 nm, debido principalmente a las propiedades fotocatalíticas del P25 en la región del ultravioleta-visible. <br /

Desulfuración de dibenzotiofeno con "pseudomonas putida" CECT5279 : formas de operación

Tesis de la Universidad Complutense de Madrid, Facultad de Ciencias Químicas, Departamento de Ingeniería Química, leída el 14-05-2010Depto. de Ingeniería Química y de MaterialesFac. de Ciencias QuímicasTRUEpu

Empleo de herramientas TIC y estrategias de gamificación en la asignatura de Técnicas Instrumentales Básicas

Se ha desarrollado un entorno virtual de aprendizaje enlazado a seis webquests para trabajar los contenidos y mejorar la experiencia de enseñanza-aprendizaje de la asignatura de Técnicas Instrumentales Básicas del Grado de Biotecnología de la Universidad Francisco de Vitoria, aprovechando herramientas TIC y la metodología de gamificación. Se trata de una acción formativa en modalidad b-learning, dirigida a 70 alumnos de segundo curso de grado universitario, para fomentar el desarrollo y empleo de competencias de alto nivel cognitivo. Se ha logrado facilitar la interacción entre estudiantes y docentes, y mejorar el seguimiento y la retroalimentación durante el curso.S'ha desenvolupat un entorn virtual d'aprenentatge enllaçat a sis webquests per treballar els continguts i millorar l'experiència d'ensenyament-aprenentatge de l'assignatura de Tècniques Instrumentals Bàsiques del Grau de Biotecnologia de la Universitat Francisco de Vitòria, aprofitant eines TIC i la metodologia de gamificació . Es tracta d'una acció formativa en modalitat b-learning, adreçada a 70 alumnes de segon curs de grau universitari, per fomentar el desenvolupament i ocupació de competències d'alt nivell cognitiu. S'ha aconseguit facilitar la interacció entre estudiants i docents, i millorar el seguiment i la retroalimentació durant el curs.A virtual learning environment linked to six webquests has been developed to work on the contents and improve the teaching-learning experience of the Basic Instrumental Techniques subject of the Biotechnology Degree at the Francisco de Vitoria University, taking advantage of ICT tools and the gamification methodology . It is a training activity in b-learning mode, aimed at 70 students in the second year of university degree, to encourage the development and use of high-level cognitive skills. It has been possible to facilitate the interaction between students and teachers, and improve the follow-up and feedback during the course

Grape Polyphenols to Arrest in Vitro Proliferation of Human Leukemia Cells: A Systematic Review and Meta-analysis.

Leukemia is a heterogeneous group of hemopoietic cancers, which accounts for 2.6% of new cases per year of total cancer incidence worldwide. Grapes and grape-derived products, such as grape juice, are naturally rich in polyphenols, bioactive compounds with antioxidant properties. Certain polyphenols have been proved to alter oxidative balance, both in inducing apoptosis in cancer cells and in preventing cancer development via controlling oxidative stress. To assess the therapeutic potential of grape polyphenols in the treatment of leukemia, a systematic review and meta-analysis of the reported data on leukemia was carried out. Following the PRISMA guide, a literature review of published papers on leukemia and polyphenols from the last 50 years was conducted, and 17 scientific articles published from 2002 to 2017 were included in the study. Resveratrol 50 μM had the highest growth inhibition effect (67%) followed by quercetin (30%). The results also point to a differential effect of polyphenols based on cell lineage; monocytes- and myelocytic-derived cell lines are the most susceptible, with a mean of 85% and 64% proliferation inhibition, respectively. Moreover, results show that growth inhibition cannot be associated with a molecular effect of polyphenols on the cell cycle arrest.pre-print303 K

Engineering alginate-based dry powder microparticles to a size suitable for the direct pulmonary delivery of antibiotics

The inhaled route is regarded as one of the most promising strategies as a treatment against pulmonary infections. However, the delivery of drugs in a dry powder form remains challenging. In this work, we have used alginate to form microparticles containing an antibiotic model (colistin sulfate). The alginate microparticles were generated by atomization technique, and they were characterized by antimicrobial in vitro studies against Pseudomonas aeruginosa. Optimization of different parameters allowed us to obtain microparticles as a dry powder with a mean size (Feret diameter) of 4.45 ± 1.40 µm and drug loading of 8.5 ± 1.50%. The process developed was able to concentrate most of the colistin deposits on the surface of the microparticles, which could be observed by SEM and a Dual-Beam microscope. This produces a fast in vitro release of the drug, with a 100% release achieved in 4 h. Physicochemical characterization using the FTIR, EDX and PXRD techniques revealed information about the change that occurs from the amorphous to a crystalline form of colistin. Finally, the cytotoxicity of microparticles was tested using lung cell lines (A549 and Calu-3). Results of the study showed that alginate microparticles were able to inhibit bacterial growth while displaying non-toxicity toward lung cells