Polymer-Grafted Mesoporous Silica Nanoparticles as Ultrasound-Responsive Drug Carriers

A new ultrasound-responsive system based on mesoporous silica nanoparticles was developed for biomedical applications, grafting a copolymer on their surface that acts as gatekeeper of the pores. The nanoparticles can be loaded with a cargo at low temperature (4 degrees C), taking advantage of the open conformation that the polymer presents under these conditions. Then, at 37 degrees C the copolymer collapses closing the pore entrances and allowing the nanoparticles to carry the drugs at physiological temperature without premature release, which is of great importance when dealing with cytotoxic drugs in cancer treatments. Upon ultrasound irradiation, the sensitive polymer changes its hydrophobicity and, therefore, its conformation toward coil-like opening the gates and releasing the cargo. These hybrid nanoparticles have been shown to be noncytotoxic and can be internalized into LNCaP cells retaining their ultrasound-responsive capability in the cytoplasm of the cells. Moreover, doxorubicin-loaded hybrid MSNs were incubated with LNCaP cells to show their capacity to induce cell death only when the nanoparticles had been exposed to ultrasound. This work demonstrates that our hybrid-MSNs can be triggered by remote stimuli, which is of capital importance for future applications in drug delivery and cancer therapy

Rehabilitación de la playa de Moncofa (Castellón)

Se lleva a cabo una rehabilitación de la playa de Moncofa en todos los aspectos. Por un lado, se re dimensionan espigones y se cambia tanto el ancho como el largo útil de la linea costera. Por otro lado, se transporta al emplazamiento de la obra árido seleccionado proveniente de cantera, para llevar a cabo una regeneración de la playa de Moncofa. Este proyecto supone un cambio sustancial en la seguridad de la zona costera afectada, que debido al notable y presente cambio meteorológico y climático la intensidad de los temporales que llegan a la costa está creciendo de manera considerable. Es por ello necesario unas estructuras de defensa litoral correctamente dimensionadas y conservadas, para que permitan una rotura de ola considerable.<br /

Quantification and isotopic analysis of intracellular sulfur metabolites in the dissimilatory sulfate reduction pathway

Microbial sulfate reduction exhibits a normal isotope effect, leaving unreacted sulfate enriched in ^(34)S and producing sulfide that is depleted in ^(34)S. However, the magnitude of sulfur isotope fractionation is quite variable. The resulting changes in sulfur isotope abundance have been used to trace microbial sulfate reduction in modern and ancient ecosystems, but the intracellular mechanism(s) underlying the wide range of fractionations remains unclear. Here we report the concentrations and isotopic ratios of sulfur metabolites in the dissimilatory sulfate reduction pathway of Desulfovibrio alaskensis. Intracellular sulfate and APS levels change depending on the growth phase, peaking at the end of exponential phase, while sulfite accumulates in the cell during stationary phase. During exponential growth, intracellular sulfate and APS are strongly enriched in ^(34)S. The fractionation between internal and external sulfate is up to 49‰, while at the same time that between external sulfate and sulfide is just a few permil. We interpret this pattern to indicate that enzymatic fractionations remain large but the net fractionation between sulfate and sulfide is muted by the closed-system limitation of intracellular sulfate. This ‘reservoir effect’ diminishes upon cessation of exponential phase growth, allowing the expression of larger net sulfur isotope fractionations. Thus, the relative rates of sulfate exchange across the membrane versus intracellular sulfate reduction should govern the overall (net) fractionation that is expressed. A strong reservoir effect due to vigorous sulfate reduction might be responsible for the well-established inverse correlation between sulfur isotope fractionation and the cell-specific rate of sulfate reduction, while at the same time intraspecies differences in sulfate uptake and/or exchange rates could account for the significant scatter in this relationship. Our approach, together with ongoing investigations of the kinetic isotope fractionation by key enzymes in the sulfate reduction pathway, should provide an empirical basis for a quantitative model relating the magnitude of microbial isotope fractionation to their environmental and physiological controls

Decidua-derived mesenchymal stem cells as carriers of mesoporous silica nanoparticles. In vitro and in vivo evaluation on mammary tumors

The potential use of human Decidua-derived mesenchymal stem cells (DMSCs) as a platform to carry mesoporous silica nanoparticles in cancer therapy has been investigated. Two types of nanoparticles were evaluated. The nanoparticles showed negligible toxicity to the cells, a fast uptake and a long retention inside them. Nanoparticle location in the cell was studied by colocalization with the lysosomes. Moreover, the in vitro and in vivo migration of DMSCs towards tumors was not modified by the evaluated nanoparticles. Finally, DMSCs transporting doxorubicin-loaded nanoparticles were capable of inducing cancer cell death in vitro

Vectorization of ultrasound-responsive nanoparticles in placental mesenchymal stem cells for cancer therapy

A new platform constituted by engineered responsive nanoparticles transported by human mesenchymal stem cells is here presented as a proof of concept. Ultrasound-responsive mesoporous silica nanoparticles are coated with polyethylenimine to favor their effective uptake by decidua-derived mesenchymal stem cells. The responsive-release ability of the designed nanoparticles is confirmed, both in vial and in vivo. In addition, this capability is maintained inside the cells used as carriers. The migration capacity of the nanoparticle-cell platform towards mammary tumors is assessed in vitro. The efficacy of this platform for anticancer therapy is shown against mammary tumor cells by inducing the release of doxorubicin only when the cell vehicles are exposed to ultrasound

Mesoporous Silica Nanoparticles Engineered for Ultrasound-Induced Uptake by Cancer Cells

A novel smart hierarchical ultrasound-responsive mesoporous silica nanocarrier for cancer therapy is here presented. This dynamic nanosystem has been designed to display different surface characteristics during its journey towards tumor cells. Initially, the anticancer-loaded nanocarriers are shielded with a polyethylene glycol layer. Upon exposure to high frequency ultrasound, the polymer shell detaches from the nanoparticles, exposing a positively-charged surface. That favors the internalization in human osteosarcoma cells, where release of topotecan takes place, drastically enhancing the cytotoxic effect

Valoración económica de las emisiones de CO2 por el cambio de uso del suelo

l Área Metropolitana de Mendoza es escenario de una expansión urbana desorganizada que produce transformaciones del suelo, generando costos ambientales, particularmente sobre el potencial de regulación climática del suelo, pero sin contemplarlos en la toma de decisiones. Por este motivo, se busca valorar económicamente estos impactos. Se plantea, como caso de estudio, un viñedo ubicado en Chacras de Coria, Luján de Cuyo. Los resultados muestran que si no se incorpora este servicio ecosistémico en el precio de venta de los terrenos hay una subestimación de su valor, lo que fomenta la forma desorganizada de crecimiento urbano

Potencial inflamatorio de la dieta y su relación con el grosor miointimal carotídeo como marcador de aterosclerosis subclínica en pacientes con hipertensión arterial

Introducción: ciertos componentes de la dieta tendrían un efecto inmunomodulador impactando en el desarrollo de la aterosclerosis. Objetivo: analizar la relación entre el potencial inflamatorio de la dieta y el grosor miointimal carotídeo (GMIC) como marcador de aterosclerosis subclínica, en pacientes hipertensos del Servicio de Cardiología del Hospital Nacional de Clínicas (SC-HNC) de Córdoba, durante 2018-2019. Metodología: estudio transversal, descriptivo y correlacional. Participaron 136 personas hipertensas de ambos sexos, entre 40 a 65 años de edad, del SC-HNC de Córdoba. Mediante encuestas validadas se analizó ingesta alimentaria, actividad física (AF) y tabaquismo. Se tomaron medidas antropométricas, bioquímicas y presión arterial (PA). El consumo alimentario se estimó con el programa Interfood v.1.3. Se evaluaron, el GMIC por ultrasonido y el potencial inflamatorio de la dieta con el índice inflamatorio de la dieta (IID). Se aplicaron el test estadístico Chi cuadrado, de Wilcoxon, y el test de correlación de Spearman. Se empleó el programa Infostat v 2018p. Resultados: el 88% presentó exceso de peso y el 74% riesgo cardiovascular (RCV) muy aumentado. El 50% realizó AF baja y el 19,1% fuma actualmente. Las concentraciones séricas de colesterol total, HDL-col y LDL-col fueron diferentes según sexo (p=0,05). Conclusión: si bien no hubo asociación entre una dieta proinflamatoria y un GMIC aumentado, la población presentó factores de riesgo cardiovasculares vinculados a la inflamación, por lo tanto, es necesario continuar investigando en el área.202

From Proof-of-Concept Material to PEGylated and Modularly Targeted Ultrasound-Responsive Mesoporous Silica Nanoparticles

In this work we present the synthesis, characterization and in vitro biological evaluation of PEGylated and actively-targeted ultrasound-responsive hybrid mesoporous silica nanoparticles. This work covers the development of the chemical strategies necessary to afford a modular nanocarrier starting from a proof-of-concept material presented in previous work. This functional ultrasound-responsive material can be adapted to different specific pathological conditions by carefully choosing the appropriate targeting moieties. The new ultrasound responsive material is able to target HeLa cells when conjugated with biotin or an RGD peptide. Ultrasound-responsive cytotoxicity towards cancer cells of doxorubicinloaded nanoparticles is demonstrated in an in vitro cytotoxicity assay