Targeting Innate Immunity with dsRNA-Conjugated Mesoporous Silica Nanoparticles Promotes Antitumor Effects on Breast Cancer Cells

The authors describe herein a Toll-like receptor 3 (TLR3) targeting delivery system based on mesoporous silica nanoparticles capped with the synthetic double stranded RNA polyinosinic-polycytidylic acid (poly(I:C)) for controlled cargo delivery in SK-BR-3 breast carcinoma cells. The authors' results show that poly(I:C)-conjugated nanoparticles efficiently targeted breast cancer cells due to dsRNA-TLR3 interaction. Such interaction also triggered apoptotic pathways in SK-BR-3, significantly decreasing cells viability. Poly(I:C) cytotoxic effect in breast carcinoma cells was enhanced by loading nanoparticles' mesopores with the anthracyclinic antibiotic doxorubicin, a commonly used chemotherapeutic agent.We thank the Spanish Government (projects SAF2010-21195 and MAT2012-38429-C04-01) and the Generalitat Valenciana (project PROMETEOII/2014/047) for support. A.U. and C.G. are grateful to the Ministry of Education, Culture and Sport for their doctoral fellowships. We thank J. M. Cosgaya and M. J. Latasa for helpful discussions.Ultimo, A.; Giménez Morales, C.; Bartovsky, P.; Aznar, E.; Sancenón Galarza, F.; Marcos Martínez, MD.; Amoros Del Toro, PJ.... (2016). Targeting Innate Immunity with dsRNA-Conjugated Mesoporous Silica Nanoparticles Promotes Antitumor Effects on Breast Cancer Cells. Chemistry - A European Journal. 22(5):1582-1586. https://doi.org/10.1002/chem.201504629S15821586225Torre, L. A., Bray, F., Siegel, R. L., Ferlay, J., Lortet-Tieulent, J., & Jemal, A. (2015). Global cancer statistics, 2012. CA: A Cancer Journal for Clinicians, 65(2), 87-108. doi:10.3322/caac.21262McGuire, A., Brown, J., Malone, C., McLaughlin, R., & Kerin, M. (2015). Effects of Age on the Detection and Management of Breast Cancer. Cancers, 7(2), 908-929. doi:10.3390/cancers7020815Stier, S., Maletzki, C., Klier, U., & Linnebacher, M. (2013). Combinations of TLR Ligands: A Promising Approach in Cancer Immunotherapy. 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Caracterización fotofísica de compuestos con actividad antitumoral

Los bencimidazoles se usan como antihelmínticos, antinématodos y antiprotozoos. La colchicina es un alcaloíde tricíclico de orígen natural. Se ha usado en el tratamiento de gota, reumatismo y fiebre mediterránea. Recientemente, su actividad antitumoral ha generado expectativas en la investigación del cáncer. La actividad antitumoral de ambos tipos de compuestos se atribuye a su capacidad de influír en la polimerización de la tubulina y como consecuencia en el proceso de mitosis. El mecanismo preciso de acción no es conocido. Por esta razón proponemos utilizar la fotólisis de destello láser (FDL) para estudiar las interacciones entre los agentes antimitóticos en estado excitado con las proteínas y las ciclodextrinas. La FDL es una técnica relativamente novedosa y con muchas ventajas. En general, se conoce poco sobre los estados excitados singlete, mientras que los estados excitados triplete no han sido descritos. La fase preliminar ha consistido en la caracterización fotofísica y fotoquímicas de los compuestos cuyas propiedades no han sido estudiadas con anterioridad. Así, se han caracterizado el estado excitado triplete del 2-aminobencimidazol, del tiabendazol y de las lumicolchicinas (por generación in situ a través de la isomerización de la colchicina). Además, para el 2-aminobencimidazol, se ha identificado el radical aminilo, cuya formación ha sido utilizada como sonda en estudios mecanísticos llevados a cabo sobre la reactividad entre el triplete de distintas cetonas aromáticas y el 2-aminobencimidazol. Se ha valorado el uso de las especies transitorias de estos fármacos como sondas en el estudio de interacción con biomoléculas y ciclodextrinas. Así, se han estudiado las interacciones del triplete del tiabendazol con ciclodextrinas de distinto tamaño.Bartovsky ., P. (2011). Caracterización fotofísica de compuestos con actividad antitumoral [Tesis doctoral no publicada]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/11798Palanci

Delivery modulation in silica mesoporous supports via functionalization in the pore outlets with a Zn(II) bis(2-pyridylmethyl)amine complex

[EN] This paper focuses on the study of the release behaviour of an entrapped dye (i.e. [Ru(bipy)3] 2+) in the presence of different anions from silica mesoporous supports functionalized in the external surface with Zn(II)–bis(2-pyridylmethyl)amine complexes (solid SZn). The Zn(II)–dipicolylamine complexes, anchored in the external surface of SZn, are too small to induce pore blockage and the loaded [Ru(bipy)3] 2+ dye is freely to diffuse from the inner of the pores to the bulk solution. Addition of selected anions (F, Cl, Br, I , AcO, BzO, SO4 2, NO3 , PO4 3, P2O7 2, ATP, ADP and AMP) modulates the release of the entrapped cargo. It was observed that the interaction of the Zn(II) complex with bulky organic phosphates (such as ATP, ADP and AMP), pyrophosphate and phosphate resulted in a remarkable inhibition of the [Ru(bipy)3] 2+ dye. Small or poorly coordinating anions induced moderate or negligible inhibitions of [Ru(bipy)3] 2+ release. The delivery observed was clearly related with the ability of the anion to form complexes with the Zn(II)–dipicolylamine groups and with the size and charge of the anion.Financial support from the Spanish Government (project MAT2012-38429-C04-01) and the Generalitat Valencia (project PROMETEO/2009/016) is gratefully acknowledged.Bartovsky, P.; Ribes, À.; Agostini, A.; Benito Beorlegui, Á.; Martínez-Máñez, R. (2014). Delivery modulation in silica mesoporous supports via functionalization in the pore outlets with a Zn(II) bis(2-pyridylmethyl)amine complex. Inorganica Chimica Acta. 417:263-269. https://doi.org/10.1016/j.ica.2014.01.036S26326941

GPU Implementation of Linear Morphological Openings with Arbitrary Angle

International audienceLinear morphological openings and closings are important non-linear operators from mathematical morphology. In practical applications, many different orientations of digital line segments must typically be considered. In this paper, we (1) review efficient sequential as well as parallel algorithms for the computation of linear openings and closings, (2) compare the performance of CPU implementations of four state-of-the-art algorithms, (3) describe GPU implementations of two recent efficient algorithms allowing arbitrary orientation of the line segments, (4) propose, as the main contribution, an efficient and optimized GPU implementation of linear openings, and (5) compare the performance of all implementations on real images from various applications. From our experimental results, it turned out that the proposed GPU implementation is suitable for applications with large, industrial images, running under severe timing constraints