31 research outputs found
Distributional chaos for backward shifts
AbstractWe provide sufficient conditions which give uniform distributional chaos for backward shift operators. We also compare distributional chaos with other well-studied notions of chaos for linear operators, like Devaney chaos and hypercyclicity, and show that Devaney chaos implies uniform distributional chaos for weighted backward shifts, but there are examples of backward shifts which are uniformly distributionally chaotic and not hypercyclic
FACTORES DE RIESGO DE MACROSOMÍA Y MORBI-MORTALIDAD PERINATAL: ESTUDIO DESCRIPTIVO
INTRODUCCIÓN - La macrosomía define a aquellos recién nacidos con un peso al nacer igual o superior a los 4000 gramos, sea cual sea la edad gestacional. Se relaciona con un riesgo aumentado de complicaciones maternas y morbimortalidad neonatal. Por este motivo es importante la detección temprana de los fetos con riesgo de macrosomía, así como su correcto manejo y seguimiento para poder evitar resultados perinatales adversos. La ecografía bidimensional es la modalidad más aceptada en la actualidad para su predicción.OBJETIVOS - Identificar los factores de riesgo asociados a la macrosomía, así como las complicaciones obstétricas y el resultado perinatal. Determinar si la incidencia de los eventos adversos que se estudian ha sido mayor cuanto mayor es el grado de macrosomía.MATERIAL Y MÉTODO - Estudio observacional, descriptivo y retrospectivo. Se revisaron los nacimientos con un peso igual o superior a 4000 gramos, que tuvieron lugar en el Hospital San Pedro de Logroño durante el segundo semestre del año 2020. De los 976 partos que tuvieron lugar en ese período de tiempo, se seleccionó una muestra de 70 pacientes. El análisis estadístico se realizó con SPSS®.RESULTADOS - La tasa de macrosomía fue de 7,17%. El IMC materno medio fue 27,97 kg/m2. Todos lo recién nacidos con un peso superior a 4500 gramos al nacimiento fueron hijos de madres con sobrepeso u obesidad. El 62,9% de los partos fueron eutócicos y el 25,2% nacieron por cesárea, siendo la indicación más frecuente la desproporción pélvico-cefálica. La distocia de hombros fue más frecuente en los RN con un peso superior a 4500 gramos. Dos neonatos precisaron ingreso en la UCI neonatal por depresión respiratoria.CONCLUSIONES - El IMC materno pregestacional elevado, la ganancia excesiva de peso durante la gestación, el antecedente de un hijo previo macrosómico y la presencia de diabetes gestacional o pregestacional materna incrementan el riesgo de macrosomía. En nuestra muestra no hubo complicaciones neonatales graves.<br /
Nanoparticle-cell-nanoparticle communication by stigmergy to enhance poly(I:C) induced apoptosis in cancer cells
[EN] Nanoparticle-cell-nanoparticle communication by stigmergy was demonstrated using two capped nanodevices. The first community of nanoparticles (i.e.S(RA)(IFN)) is loaded with 9-cis-retinoic acid and capped with interferon-gamma, whereas the second community of nanoparticles (i.e.S(sulf)(PIC)) is loaded with sulforhodamine B and capped with poly(I:C). The uptake ofS(RA)(IFN)by SK-BR-3 breast cancer cells enhanced the expression of TLR3 receptor facilitating the subsequent uptake ofS(sulf)(PIC)and cell killing.We thank the Spanish Government (projects RTI2018-100910-B-C41 and RTI2018-101599-B-C22 (MCUI/FEDER, EU)), Generalitat Valenciana (project PROMETEO2018/024) and CIBER-BBN (project NANOCOMMUNITY) for support. A. U. and C. G are grateful to the Ministry of Education, Culture and Sport for her doctoral FPU grant.Ultimo, A.; De La Torre-Paredes, C.; Giménez, C.; Aznar, E.; Coll, C.; Marcos Martínez, MD.; Murguía, JR.... (2020). Nanoparticle-cell-nanoparticle communication by stigmergy to enhance poly(I:C) induced apoptosis in cancer cells. Chemical Communications. 56(53):7273-7276. https://doi.org/10.1039/d0cc02795bS727372765653Schaming, D., & Remita, H. (2015). Nanotechnology: from the ancient time to nowadays. Foundations of Chemistry, 17(3), 187-205. doi:10.1007/s10698-015-9235-yHauert, S., & Bhatia, S. N. (2014). Mechanisms of cooperation in cancer nanomedicine: towards systems nanotechnology. Trends in Biotechnology, 32(9), 448-455. doi:10.1016/j.tibtech.2014.06.010Theraulaz, G., & Bonabeau, E. (1999). A Brief History of Stigmergy. Artificial Life, 5(2), 97-116. doi:10.1162/106454699568700Llopis-Lorente, A., Díez, P., Sánchez, A., Marcos, M. D., Sancenón, F., Martínez-Ruiz, P., … Martínez-Máñez, R. (2017). Interactive models of communication at the nanoscale using nanoparticles that talk to one another. Nature Communications, 8(1). doi:10.1038/ncomms15511Luis, B., Llopis‐Lorente, A., Rincón, P., Gadea, J., Sancenón, F., Aznar, E., … Martínez‐Máñez, R. (2019). An Interactive Model of Communication between Abiotic Nanodevices and Microorganisms. Angewandte Chemie International Edition, 58(42), 14986-14990. doi:10.1002/anie.201908867De la Torre, C., Domínguez-Berrocal, L., Murguía, J. R., Marcos, M. D., Martínez-Máñez, R., Bravo, J., & Sancenón, F. (2018). ϵ
-Polylysine-Capped Mesoporous Silica Nanoparticles as Carrier of the C
9h
Peptide to Induce Apoptosis in Cancer Cells. Chemistry - A European Journal, 24(8), 1890-1897. doi:10.1002/chem.201704161García-Fernández, A., García-Laínez, G., Ferrándiz, M. L., Aznar, E., Sancenón, F., Alcaraz, M. J., … Orzáez, M. (2017). Targeting inflammasome by the inhibition of caspase-1 activity using capped mesoporous silica nanoparticles. Journal of Controlled Release, 248, 60-70. doi:10.1016/j.jconrel.2017.01.002Murugan, C., Rayappan, K., Thangam, R., Bhanumathi, R., Shanthi, K., Vivek, R., … Kannan, S. (2016). Combinatorial nanocarrier based drug delivery approach for amalgamation of anti-tumor agents in breast cancer cells: an improved nanomedicine strategy. Scientific Reports, 6(1). doi:10.1038/srep34053Van Rijt, S. H., Bölükbas, D. A., Argyo, C., Datz, S., Lindner, M., Eickelberg, O., … Meiners, S. (2015). Protease-Mediated Release of Chemotherapeutics from Mesoporous Silica Nanoparticles to ex Vivo Human and Mouse Lung Tumors. ACS Nano, 9(3), 2377-2389. doi:10.1021/nn5070343Llopis-Lorente, A., Lozano-Torres, B., Bernardos, A., Martínez-Máñez, R., & Sancenón, F. (2017). Mesoporous silica materials for controlled delivery based on enzymes. Journal of Materials Chemistry B, 5(17), 3069-3083. doi:10.1039/c7tb00348jBianchi, F., Pretto, S., Tagliabue, E., Balsari, A., & Sfondrini, L. (2017). Exploiting poly(I:C) to induce cancer cell apoptosis. Cancer Biology & Therapy, 18(10), 747-756. doi:10.1080/15384047.2017.1373220Ultimo, A., Giménez, C., Bartovsky, P., Aznar, E., Sancenón, F., Marcos, M. D., … Murguía, J. R. (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. doi:10.1002/chem.201504629Bernardo, A. R., Cosgaya, J. M., Aranda, A., & Jiménez-Lara, A. M. (2013). Synergy between RA and TLR3 promotes type I IFN-dependent apoptosis through upregulation of TRAIL pathway in breast cancer cells. Cell Death & Disease, 4(1), e479-e479. doi:10.1038/cddis.2013.5Clarke, N., Jimenez-Lara, A. M., Voltz, E., & Gronemeyer, H. (2004). Tumor suppressor IRF-1 mediates retinoid and interferon anticancer signaling to death ligand TRAIL. The EMBO Journal, 23(15), 3051-3060. doi:10.1038/sj.emboj.7600302Kajita, A. i., Morizane, S., Takiguchi, T., Yamamoto, T., Yamada, M., & Iwatsuki, K. (2015). Interferon-Gamma Enhances TLR3 Expression and Anti-Viral Activity in Keratinocytes. Journal of Investigative Dermatology, 135(8), 2005-2011. doi:10.1038/jid.2015.125Weihua, X., Kolla, V., & Kalvakolanu, D. V. (1997). Modulation of Interferon Action by Retinoids. Journal of Biological Chemistry, 272(15), 9742-9748. doi:10.1074/jbc.272.15.974
Glucose-triggered release using enzyme-gated mesoporous silica nanoparticles
[EN] A new gated nanodevice design able to control cargo delivery using glucose as a trigger and cyclodextrin-modified glucose oxidase as a capping agent is reported.Financial support from the Spanish Government (projects MAT2012-38429-C04-01 and CTQ2011-24355), Generalitat Valenciana (project PROMETEO/2009/016), UPV (project SP20120795) and Ramon y Cajal Programme (to R. V.) is gratefully acknowledged.Aznar Gimeno, E.; Villalonga, R.; Giménez Morales, C.; Sancenón Galarza, F.; Marcos Martínez, MD.; Martínez Mañez, R.; Díez, P.... (2013). Glucose-triggered release using enzyme-gated mesoporous silica nanoparticles. Chemical Communications. 49(57):6391-6393. https://doi.org/10.1039/c3cc42210kS639163934957Coll, C., Bernardos, A., Martínez-Máñez, R., & Sancenón, F. (2012). Gated Silica Mesoporous Supports for Controlled Release and Signaling Applications. Accounts of Chemical Research, 46(2), 339-349. doi:10.1021/ar3001469Aznar, E., Martínez-Máñez, R., & Sancenón, F. (2009). Controlled release using mesoporous materials containing gate-like scaffoldings. Expert Opinion on Drug Delivery, 6(6), 643-655. doi:10.1517/17425240902895980Cotí, K. K., Belowich, M. E., Liong, M., Ambrogio, M. W., Lau, Y. A., Khatib, H. A., … Stoddart, J. F. (2009). Mechanised nanoparticles for drug delivery. Nanoscale, 1(1), 16. doi:10.1039/b9nr00162jKresge, C. T., Leonowicz, M. E., Roth, W. J., Vartuli, J. C., & Beck, J. S. (1992). Ordered mesoporous molecular sieves synthesized by a liquid-crystal template mechanism. Nature, 359(6397), 710-712. doi:10.1038/359710a0Lai, C.-Y., Trewyn, B. G., Jeftinija, D. M., Jeftinija, K., Xu, S., Jeftinija, S., & Lin, V. S.-Y. (2003). A Mesoporous Silica Nanosphere-Based Carrier System with Chemically Removable CdS Nanoparticle Caps for Stimuli-Responsive Controlled Release of Neurotransmitters and Drug Molecules. Journal of the American Chemical Society, 125(15), 4451-4459. doi:10.1021/ja028650lPark, C., Oh, K., Lee, S. C., & Kim, C. (2007). Controlled Release of Guest Molecules from Mesoporous Silica Particles Based on a pH-Responsive Polypseudorotaxane Motif. Angewandte Chemie International Edition, 46(9), 1455-1457. doi:10.1002/anie.200603404Casasús, R., Climent, E., Marcos, M. D., Martínez-Máñez, R., Sancenón, F., Soto, J., … Ruiz, E. (2008). Dual Aperture Control on pH- and Anion-Driven Supramolecular Nanoscopic Hybrid Gate-like Ensembles. Journal of the American Chemical Society, 130(6), 1903-1917. doi:10.1021/ja0756772Liu, R., Liao, P., Liu, J., & Feng, P. (2011). Responsive Polymer-Coated Mesoporous Silica as a pH-Sensitive Nanocarrier for Controlled Release. Langmuir, 27(6), 3095-3099. doi:10.1021/la104973jCliment, E., Martínez-Máñez, R., Sancenón, F., Marcos, M. D., Soto, J., Maquieira, A., & Amorós, P. (2010). Controlled Delivery Using Oligonucleotide-Capped Mesoporous Silica Nanoparticles. Angewandte Chemie International Edition, 49(40), 7281-7283. doi:10.1002/anie.201001847Mal, N. K., Fujiwara, M., & Tanaka, Y. (2003). Photocontrolled reversible release of guest molecules from coumarin-modified mesoporous silica. Nature, 421(6921), 350-353. doi:10.1038/nature01362Fu, Q., Rao, G. V. R., Ista, L. K., Wu, Y., Andrzejewski, B. P., Sklar, L. A., … López, G. P. (2003). Control of Molecular Transport Through Stimuli-Responsive Ordered Mesoporous Materials. Advanced Materials, 15(15), 1262-1266. doi:10.1002/adma.200305165Aznar, E., Mondragón, L., Ros-Lis, J. V., Sancenón, F., Marcos, M. D., Martínez-Máñez, R., … Amorós, P. (2011). Finely Tuned Temperature-Controlled Cargo Release Using Paraffin-Capped Mesoporous Silica Nanoparticles. Angewandte Chemie International Edition, 50(47), 11172-11175. doi:10.1002/anie.201102756Bringas, E., Köysüren, Ö., Quach, D. V., Mahmoudi, M., Aznar, E., Roehling, J. D., … Stroeve, P. (2012). Triggered release in lipid bilayer-capped mesoporous silica nanoparticles containing SPION using an alternating magnetic field. Chemical Communications, 48(45), 5647. doi:10.1039/c2cc31563gPatel, K., Angelos, S., Dichtel, W. R., Coskun, A., Yang, Y.-W., Zink, J. I., & Stoddart, J. F. (2008). Enzyme-Responsive Snap-Top Covered Silica Nanocontainers. Journal of the American Chemical Society, 130(8), 2382-2383. doi:10.1021/ja0772086Schlossbauer, A., Kecht, J., & Bein, T. (2009). Biotin-Avidin as a Protease-Responsive Cap System for Controlled Guest Release from Colloidal Mesoporous Silica. Angewandte Chemie International Edition, 48(17), 3092-3095. doi:10.1002/anie.200805818Park, C., Kim, H., Kim, S., & Kim, C. (2009). Enzyme Responsive Nanocontainers with Cyclodextrin Gatekeepers and Synergistic Effects in Release of Guests. Journal of the American Chemical Society, 131(46), 16614-16615. doi:10.1021/ja9061085Bernardos, A., Mondragón, L., Aznar, E., Marcos, M. D., Martínez-Máñez, R., Sancenón, F., … Amorós, P. (2010). Enzyme-Responsive Intracellular Controlled Release Using Nanometric Silica Mesoporous Supports Capped with «Saccharides». ACS Nano, 4(11), 6353-6368. doi:10.1021/nn101499dAgostini, A., Mondragón, L., Bernardos, A., Martínez-Máñez, R., Marcos, M. D., Sancenón, F., … Murguía, J. R. (2012). Targeted Cargo Delivery in Senescent Cells Using Capped Mesoporous Silica Nanoparticles. Angewandte Chemie International Edition, 51(42), 10556-10560. doi:10.1002/anie.201204663Schlossbauer, A., Warncke, S., Gramlich, P. M. E., Kecht, J., Manetto, A., Carell, T., & Bein, T. (2010). A Programmable DNA-Based Molecular Valve for Colloidal Mesoporous Silica. Angewandte Chemie International Edition, 49(28), 4734-4737. doi:10.1002/anie.201000827Climent, E., Bernardos, A., Martínez-Máñez, R., Maquieira, A., Marcos, M. D., Pastor-Navarro, N., … Amorós, P. (2009). Controlled Delivery Systems Using Antibody-Capped Mesoporous Nanocontainers. Journal of the American Chemical Society, 131(39), 14075-14080. doi:10.1021/ja904456dZhao, Y., Trewyn, B. G., Slowing, I. I., & Lin, V. S.-Y. (2009). Mesoporous Silica Nanoparticle-Based Double Drug Delivery System for Glucose-Responsive Controlled Release of Insulin and Cyclic AMP. Journal of the American Chemical Society, 131(24), 8398-8400. doi:10.1021/ja901831uHolzinger, M., Bouffier, L., Villalonga, R., & Cosnier, S. (2009). Adamantane/β-cyclodextrin affinity biosensors based on single-walled carbon nanotubes. Biosensors and Bioelectronics, 24(5), 1128-1134. doi:10.1016/j.bios.2008.06.029Oliver, N. S., Toumazou, C., Cass, A. E. G., & Johnston, D. G. (2009). Glucose sensors: a review of current and emerging technology. Diabetic Medicine, 26(3), 197-210. doi:10.1111/j.1464-5491.2008.02642.xWu, Q., Wang, L., Yu, H., Wang, J., & Chen, Z. (2011). Organization of Glucose-Responsive Systems and Their Properties. Chemical Reviews, 111(12), 7855-7875. doi:10.1021/cr200027jXu, Y., Pehrsson, P. E., Chen, L., Zhang, R., & Zhao, W. (2007). Double-Stranded DNA Single-Walled Carbon Nanotube Hybrids for Optical Hydrogen Peroxide and Glucose Sensing. The Journal of Physical Chemistry C, 111(24), 8638-8643. doi:10.1021/jp0709611Song, C., Pehrsson, P. E., & Zhao, W. (2006). Optical enzymatic detection of glucose based on hydrogen peroxide-sensitive HiPco carbon nanotubes. Journal of Materials Research, 21(11), 2817-2823. doi:10.1557/jmr.2006.0343Badugu, R., Lakowicz, J. R., & Geddes, C. D. (2004). Noninvasive Continuous Monitoring of Physiological Glucose Using a Monosaccharide-Sensing Contact Lens. Analytical Chemistry, 76(3), 610-618. doi:10.1021/ac030372
Gated Mesoporous Silica Nanocarriers for a "two-Step" Targeted System to Colonic Tissue
[EN] Colon targeted drug delivery is highly relevant not only to treat colonic local diseases but also for systemic therapies. Mesoporous silica nanoparticles (MSNs) have been demonstrated as useful systems for controlled drug release given their biocompatibility and the possibility of designing gated systems able to release cargo only upon the presence of certain stimuli. We report herein the preparation of three gated MSNs able to deliver their cargo triggered by different stimuli (redox ambient (S1), enzymatic hydrolysis (S2), and a surfactant or being in contact with cell membrane (S3)) and their performance in solution and in vitro with Caco-2 cells. Safranin O dye was used as a model drug to track cargo fate. Studies of cargo permeability in Caco-2 monolayers demonstrated that intracellular safranin O levels were significantly higher in Caco-2 monolayers when using MSNs compared to those of free dye. Internalization assays indicated that S2 nanoparticles were taken up by cells via endocytosis. S2 nanoparticles were selected for in vivo tests in rats. For in vivo assays, capsules were filled with S2 nanoparticles and coated with Eudragit FS 30 D to target colon. The enteric coated capsule containing the MSNs was able to deliver S2 nanoparticles in colon tissue (first step), and then nanoparticles were able to deliver safranin O inside the colonic cells after the enzymatic stimuli (second step). This resulted in high levels of safranin O in colonic tissue combined with low dye levels in plasma and body tissues. The results suggested that this combination of enzyme-responsive gated MSNs and enteric coated capsules may improve the absorption of drugs in colon to treat local diseases with a reduction of systemic effects.The authors acknowledge the financial support from the Spanish Government (Projects MAT2015-64139-C4-1-R, SAF2016-78756 and AGL2015-70235-C2-2-R) and the Generalitat Valenciana (Project GVA/2014/13).Gonzalez-Alvarez, M.; Coll Merino, MC.; Gonzalez-Alvarez, I.; Giménez Morales, C.; Aznar, E.; Martínez-Bisbal, M.; Lozoya Agulló, I.... (2017). Gated Mesoporous Silica Nanocarriers for a "two-Step" Targeted System to Colonic Tissue. Molecular Pharmaceutics. 14(12):4442-4453. https://doi.org/10.1021/acs.molpharmaceut.7b00565S44424453141
Distributional chaos for operators with full scrambled sets
In this article we answer in the negative the question of whether hypercyclicity is sufficient for distributional chaos for a continuous linear operator (we even prove that the mixing property does not suffice). Moreover, we show that an extremal situation is possible: There are (hypercyclic and non-hypercyclic) operators such that the whole space consists, except zero, of distributionally irregular vectors.The research of first and third author was supported by MEC and FEDER, project MTM2010-14909 and by GV, Project PROMETEO/2008/101. The research of second author was supported by the Marie Curie European Reintegration Grant of the European Commission under grant agreement no. PERG08-GA-2010-272297. The financial support of these institutions is hereby gratefully acknowledged. We also want to thank X. Barrachina for pointing out to us a gap in the proof of a previous version of Theorem 3.1.Martínez Jiménez, F.; Oprocha, P.; Peris Manguillot, A. (2013). Distributional chaos for operators with full scrambled sets. Mathematische Zeitschrift. 274(1-2):603-612. https://doi.org/10.1007/s00209-012-1087-8S6036122741-2Banks, J., Brooks, J., Cairns, G., Davis, G., Stacey, P.: On Devaney’s definition of chaos. Am. Math. Monthly 99(4), 332–334 (1992)Barrachina, X., Peris, A.: Distributionally chaotic translation semigroups. J. Differ. Equ. Appl. 18, 751–761 (2012)Beauzamy, B.: Introduction to Operator Theory and Invariant Subspaces. North-Holland, Amsterdam (1988)Bermúdez, T., Bonilla, A., Martínez-Giménez, F., Peris, A.: Li–Yorke and distributionally chaotic operators. J. Math. Anal. Appl. 373, 83–93 (2011)Bayart, F., Matheron, E.: Dynamics of linear operators, vol. 179. Cambridge University Press, London(2009).Costakis, G., Sambarino, M.: Topologically mixing hypercyclic operators. Proc. Am. Math. Soc. 132, 385–389 (2004)Devaney, R.L.: An introduction to chaotic dynamical systems, 2nd edn. Addison-Wesley Studies in Nonlinearity. Addison-Wesley Publishing Company Advanced Book Program. Redwood City (1989)Feldman, N.: Hypercyclicity and supercyclicity for invertible bilateral weighted shifts. Proc. Am. Math. Soc. 131, 479–485 (2003)Grosse-Erdmann, K.-G.: Hypercyclic and chaotic weighted shifts. Studia Math. 139(1), 47–68 (2000)Grosse-Erdmann, K.-G., Peris Manguillot, A.: Linear Chaos. Universitext, Springer, London (2011)Hou, B., Cui, P., Cao, Y.: Chaos for Cowen-Douglas operators. Proc. Am. Math. Soc 138, 929–936 (2010)Hou, B., Tian, G., Shi, L.: Some dynamical properties for linear operators. Ill. J. Math. 53, 857–864 (2009)Li, T.Y., Yorke, J.A.: Period three implies chaos. Am. Math. Monthly 82(10), 985–992 (1975)Martínez-Giménez, F., Oprocha, P., Peris, A.: Distributional chaos for backward shifts. J. Math. Anal. Appl. 351, 607–615 (2009)Müller, V., Peris, A.: A Problem of Beauzamy on Irregular Operators (2011). (Preprint)Oprocha, P.: Distributional chaos revisited. Trans. Am. Math. Soc. 361, 4901–4925 (2009)Oprocha, P.: A quantum harmonic oscillator and strong chaos. J. Phys. A 39(47), 14559–14565 (2006)Schweizer, B., Smítal, J.: Measures of chaos and a spectral decomposition of dynamical systems on the interval. Trans. Am. Math. Soc. 344(2), 737–754 (1994)Wu, X., Zhu, P.: The principal measure of a quantum harmonic oscillator. J. Phys. A 44(505101), 6 (2011
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. Clinical and Developmental Immunology, 2013, 1-14. doi:10.1155/2013/271246Huang, B., Zhao, J., Li, H., He, K.-L., Chen, Y., Mayer, L., … Xiong, H. (2005). Toll-Like Receptors on Tumor Cells Facilitate Evasion of Immune Surveillance. Cancer Research, 65(12), 5009-5014. doi:10.1158/0008-5472.can-05-0784Salaun, B., Coste, I., Rissoan, M.-C., Lebecque, S. J., & Renno, T. (2006). TLR3 Can Directly Trigger Apoptosis in Human Cancer Cells. The Journal of Immunology, 176(8), 4894-4901. doi:10.4049/jimmunol.176.8.4894Salaun, B., Zitvogel, L., Asselin-Paturel, C., Morel, Y., Chemin, K., Dubois, C., … Andre, F. (2011). TLR3 as a Biomarker for the Therapeutic Efficacy of Double-stranded RNA in Breast Cancer. Cancer Research, 71(5), 1607-1614. doi:10.1158/0008-5472.can-10-3490Mal, N. K., Fujiwara, M., & Tanaka, Y. (2003). Photocontrolled reversible release of guest molecules from coumarin-modified mesoporous silica. Nature, 421(6921), 350-353. doi:10.1038/nature01362Casasús, R., Climent, E., Marcos, M. D., Martínez-Máñez, R., Sancenón, F., Soto, J., … Ruiz, E. (2008). Dual Aperture Control on pH- and Anion-Driven Supramolecular Nanoscopic Hybrid Gate-like Ensembles. Journal of the American Chemical Society, 130(6), 1903-1917. doi:10.1021/ja0756772Climent, E., Martínez-Máñez, R., Sancenón, F., Marcos, M. D., Soto, J., Maquieira, A., & Amorós, P. (2010). Controlled Delivery Using Oligonucleotide-Capped Mesoporous Silica Nanoparticles. Angewandte Chemie International Edition, 49(40), 7281-7283. doi:10.1002/anie.201001847Climent, E., Martínez-Máñez, R., Sancenón, F., Marcos, M. D., Soto, J., Maquieira, A., & Amorós, P. (2010). Controlled Delivery Using Oligonucleotide-Capped Mesoporous Silica Nanoparticles. Angewandte Chemie, 122(40), 7439-7441. doi:10.1002/ange.201001847Lai, C.-Y., Trewyn, B. G., Jeftinija, D. M., Jeftinija, K., Xu, S., Jeftinija, S., & Lin, V. S.-Y. (2003). A Mesoporous Silica Nanosphere-Based Carrier System with Chemically Removable CdS Nanoparticle Caps for Stimuli-Responsive Controlled Release of Neurotransmitters and Drug Molecules. Journal of the American Chemical Society, 125(15), 4451-4459. doi:10.1021/ja028650lLiu, R., Liao, P., Liu, J., & Feng, P. (2011). Responsive Polymer-Coated Mesoporous Silica as a pH-Sensitive Nanocarrier for Controlled Release. Langmuir, 27(6), 3095-3099. doi:10.1021/la104973jPark, C., Oh, K., Lee, S. C., & Kim, C. (2007). Controlled Release of Guest Molecules from Mesoporous Silica Particles Based on a pH-Responsive Polypseudorotaxane Motif. Angewandte Chemie International Edition, 46(9), 1455-1457. doi:10.1002/anie.200603404Park, C., Oh, K., Lee, S. C., & Kim, C. (2007). Controlled Release of Guest Molecules from Mesoporous Silica Particles Based on a pH-Responsive Polypseudorotaxane Motif. Angewandte Chemie, 119(9), 1477-1479. doi:10.1002/ange.200603404Aznar, E., Mondragón, L., Ros-Lis, J. V., Sancenón, F., Marcos, M. D., Martínez-Máñez, R., … Amorós, P. (2011). Finely Tuned Temperature-Controlled Cargo Release Using Paraffin-Capped Mesoporous Silica Nanoparticles. Angewandte Chemie International Edition, 50(47), 11172-11175. doi:10.1002/anie.201102756Aznar, E., Mondragón, L., Ros-Lis, J. V., Sancenón, F., Marcos, M. D., Martínez-Máñez, R., … Amorós, P. (2011). Finely Tuned Temperature-Controlled Cargo Release Using Paraffin-Capped Mesoporous Silica Nanoparticles. Angewandte Chemie, 123(47), 11368-11371. doi:10.1002/ange.201102756Bringas, E., Köysüren, Ö., Quach, D. V., Mahmoudi, M., Aznar, E., Roehling, J. D., … Stroeve, P. (2012). Triggered release in lipid bilayer-capped mesoporous silica nanoparticles containing SPION using an alternating magnetic field. Chemical Communications, 48(45), 5647. doi:10.1039/c2cc31563gFu, Q., Rao, G. V. R., Ista, L. K., Wu, Y., Andrzejewski, B. P., Sklar, L. A., … López, G. P. (2003). Control of Molecular Transport Through Stimuli-Responsive Ordered Mesoporous Materials. Advanced Materials, 15(15), 1262-1266. doi:10.1002/adma.200305165Bernardos, A., Mondragón, L., Aznar, E., Marcos, M. D., Martínez-Máñez, R., Sancenón, F., … Amorós, P. (2010). Enzyme-Responsive Intracellular Controlled Release Using Nanometric Silica Mesoporous Supports Capped with «Saccharides». ACS Nano, 4(11), 6353-6368. doi:10.1021/nn101499dCliment, E., Bernardos, A., Martínez-Máñez, R., Maquieira, A., Marcos, M. D., Pastor-Navarro, N., … Amorós, P. (2009). Controlled Delivery Systems Using Antibody-Capped Mesoporous Nanocontainers. Journal of the American Chemical Society, 131(39), 14075-14080. doi:10.1021/ja904456dPark, C., Kim, H., Kim, S., & Kim, C. (2009). Enzyme Responsive Nanocontainers with Cyclodextrin Gatekeepers and Synergistic Effects in Release of Guests. Journal of the American Chemical Society, 131(46), 16614-16615. doi:10.1021/ja9061085Patel, K., Angelos, S., Dichtel, W. R., Coskun, A., Yang, Y.-W., Zink, J. I., & Stoddart, J. F. (2008). Enzyme-Responsive Snap-Top Covered Silica Nanocontainers. Journal of the American Chemical Society, 130(8), 2382-2383. doi:10.1021/ja0772086Schlossbauer, A., Kecht, J., & Bein, T. (2009). Biotin-Avidin as a Protease-Responsive Cap System for Controlled Guest Release from Colloidal Mesoporous Silica. Angewandte Chemie International Edition, 48(17), 3092-3095. doi:10.1002/anie.200805818Schlossbauer, A., Kecht, J., & Bein, T. (2009). Biotin-Avidin as a Protease-Responsive Cap System for Controlled Guest Release from Colloidal Mesoporous Silica. Angewandte Chemie, 121(17), 3138-3141. doi:10.1002/ange.200805818Schlossbauer, A., Warncke, S., Gramlich, P. M. E., Kecht, J., Manetto, A., Carell, T., & Bein, T. (2010). A Programmable DNA-Based Molecular Valve for Colloidal Mesoporous Silica. Angewandte Chemie International Edition, 49(28), 4734-4737. doi:10.1002/anie.201000827Schlossbauer, A., Warncke, S., Gramlich, P. M. E., Kecht, J., Manetto, A., Carell, T., & Bein, T. (2010). Ein programmierbares, DNA-basiertes molekulares Ventil für kolloidales, mesoporöses Siliciumoxid. Angewandte Chemie, 122(28), 4842-4845. doi:10.1002/ange.201000827Agostini, A., Mondragón, L., Pascual, L., Aznar, E., Coll, C., Martínez-Máñez, R., … Gil, S. (2012). Design of Enzyme-Mediated Controlled Release Systems Based on Silica Mesoporous Supports Capped with Ester-Glycol Groups. Langmuir, 28(41), 14766-14776. doi:10.1021/la303161eKresge, C. T., Leonowicz, M. E., Roth, W. J., Vartuli, J. C., & Beck, J. S. (1992). Ordered mesoporous molecular sieves synthesized by a liquid-crystal template mechanism. Nature, 359(6397), 710-712. doi:10.1038/359710a0Knežević, N. Ž., & Durand, J.-O. (2015). Targeted Treatment of Cancer with Nanotherapeutics Based on Mesoporous Silica Nanoparticles. ChemPlusChem, 80(1), 26-36. doi:10.1002/cplu.201402369Peer, D., Karp, J. M., Hong, S., Farokhzad, O. C., Margalit, R., & Langer, R. (2007). Nanocarriers as an emerging platform for cancer therapy. Nature Nanotechnology, 2(12), 751-760. doi:10.1038/nnano.2007.387Petros, R. A., & DeSimone, J. M. (2010). Strategies in the design of nanoparticles for therapeutic applications. Nature Reviews Drug Discovery, 9(8), 615-627. doi:10.1038/nrd2591Wagner, V., Dullaart, A., Bock, A.-K., & Zweck, A. (2006). The emerging nanomedicine landscape. Nature Biotechnology, 24(10), 1211-1217. doi:10.1038/nbt1006-1211Agostini, A., Mondragón, L., Bernardos, A., Martínez-Máñez, R., Marcos, M. D., Sancenón, F., … Murguía, J. R. (2012). Targeted Cargo Delivery in Senescent Cells Using Capped Mesoporous Silica Nanoparticles. Angewandte Chemie International Edition, 51(42), 10556-10560. doi:10.1002/anie.201204663Agostini, A., Mondragón, L., Bernardos, A., Martínez-Máñez, R., Marcos, M. D., Sancenón, F., … Murguía, J. R. (2012). Targeted Cargo Delivery in Senescent Cells Using Capped Mesoporous Silica Nanoparticles. Angewandte Chemie, 124(42), 10708-10712. doi:10.1002/ange.201204663Xie, M., Shi, H., Li, Z., Shen, H., Ma, K., Li, B., … Jin, Y. (2013). A multifunctional mesoporous silica nanocomposite for targeted delivery, controlled release of doxorubicin and bioimaging. Colloids and Surfaces B: Biointerfaces, 110, 138-147. doi:10.1016/j.colsurfb.2013.04.009Wang, Y., Shi, W., Song, W., Wang, L., Liu, X., Chen, J., & Huang, R. (2012). Tumor cell targeted delivery by specific peptide-modified mesoporous silica nanoparticles. Journal of Materials Chemistry, 22(29), 14608. doi:10.1039/c2jm32398bFerris, D. P., Lu, J., Gothard, C., Yanes, R., Thomas, C. R., Olsen, J.-C., … Zink, J. I. (2011). Synthesis of Biomolecule-Modified Mesoporous Silica Nanoparticles for Targeted Hydrophobic Drug Delivery to Cancer Cells. Small, 7(13), 1816-1826. doi:10.1002/smll.201002300Tsai, C.-P., Chen, C.-Y., Hung, Y., Chang, F.-H., & Mou, C.-Y. (2009). Monoclonal antibody-functionalized mesoporous silica nanoparticles (MSN) for selective targeting breast cancer cells. Journal of Materials Chemistry, 19(32), 5737. doi:10.1039/b905158aBernardo, A. R., Cosgaya, J. M., Aranda, A., & Jiménez-Lara, A. M. (2013). Synergy between RA and TLR3 promotes type I IFN-dependent apoptosis through upregulation of TRAIL pathway in breast cancer cells. Cell Death & Disease, 4(1), e479-e479. doi:10.1038/cddis.2013.5Patel, S., Sprung, A. U., Keller, B. A., Heaton, V. J., & Fisher, L. M. (1997). Identification of Yeast DNA Topoisomerase II Mutants Resistant to the Antitumor Drug Doxorubicin: Implications for the Mechanisms of Doxorubicin Action and Cytotoxicity. Molecular Pharmacology, 52(4), 658-666. doi:10.1124/mol.52.4.658Lyu, Y. L., Kerrigan, J. E., Lin, C.-P., Azarova, A. M., Tsai, Y.-C., Ban, Y., & Liu, L. F. (2007). Topoisomerase II Mediated DNA Double-Strand Breaks: Implications in Doxorubicin Cardiotoxicity and Prevention by Dexrazoxane. Cancer Research, 67(18), 8839-8846. doi:10.1158/0008-5472.can-07-1649Galluzzi, L., Vacchelli, E., Eggermont, A., Fridman, W. H., Galon, J., Sautès-Fridman, C., … Kroemer, G. (2012). Trial Watch. OncoImmunology, 1(5), 699-739. doi:10.4161/onci.20696Paone, A., Starace, D., Galli, R., Padula, F., De Cesaris, P., Filippini, A., … Riccioli, A. (2008). Toll-like receptor 3 triggers apoptosis of human prostate cancer cells through a PKC- -dependent mechanism. Carcinogenesis, 29(7), 1334-1342. doi:10.1093/carcin/bgn14
Gated mesoporous silica nanoparticles for the controlled delivery of drugs in cancer cells
In recent years, mesoporous silica nanoparticles (MSNs) have been used as effective supports for the development of controlled-release nanodevices that are able to act as multifunctional delivery platforms for the encapsulation of therapeutic agents, enhancing their bioavailability and overcoming common issues such as poor water solubility and poor stability of some drugs. In particular, redox-responsive delivery systems have attracted the attention of scientists because of the intracellular reductive environment related to a high concentration of glutathione (GSH). In this context, we describe herein the development of a GSH-responsive delivery system based on poly(ethylene glycol)- (PEG-) capped MSNs that are able to deliver safranin O and doxorubicin in a controlled manner. The results showed that the PEG-capped systems designed in this work can be maintained closed at low GSH concentrations, yet the cargo can be delivered when the concentration of GSH is increased. Moreover, the efficacy of the PEG-capped system in delivering the cytotoxic agent doxorubicin in cells was also demonstrated.The authors thank the Spanish Government (Project MAT2012-38429-C04-01), the Generalitat Valenciana (Project PROMETEOII/2014/047), and the Universitat Politecnica de Valencia (Project SP20120795) for support. C.G. and C.d.l.T also thank the Spanish Ministry of Education for their FPU grants. The authors also thank UPV electron microscopy and CIPF confocal microscopy services for technical support.Giménez Morales, C.; De La Torre, C.; Gorbe, M.; Aznar, E.; Sancenón Galarza, F.; Murguía, JR.; Martínez-Máñez, R.... (2015). Gated mesoporous silica nanoparticles for the controlled delivery of drugs in cancer cells. Langmuir. 31(12):3753-3762. https://doi.org/10.1021/acs.langmuir.5b00139S37533762311
Toward chemical communication between nanodevices
[EN] Although many nanodevices have been described in recent years, nanoparticles capable of communicating with each other have been barely reported. Traditional communication technologies cannot be applied on the nanoscale, but a potential approach to achieve this goal is to mimic how nature communicates by exchanging information using molecules. Based on these concepts, some examples using DNA, enzymes and small molecules for information processing, nanoparticles capable of modulating chemical communication between cells and nanoparticles that can communicate with each another have been reported. Communication between nanodevices may find applications in different areas and a number of future new results are envisioned in this research field. (C) 2017 Elsevier Ltd. All rights reserved.A. Llopis-Lorente is thankful to the La Caixa Banking Foundation for his PhD grant. The authors are grateful to the Spanish Government (MINECO Projects MAT2015-64139-C4-1, CTQ2014-58989-P, CTQ2015-71936-REDT and AGL2015-70235-C2-2-R) and the Generalitat Valenciana (Project PROMETEOII/2014/047). The authors also thank the Comunidad de Madrid (S2013/MIT-3029, Programme NANOAVANSENS) for support.Llopis-Lorente, A.; Diez-Sánchez, P.; Sánchez, A.; Marcos Martínez, MD.; Sancenón Galarza, F.; Martinez-Ruiz, P.; Villalonga, R.... (2018). Toward chemical communication between nanodevices. Nano Today. 18:8-11. https://doi.org/10.1016/j.nantod.2017.09.003S8111
Self-Immolative Linkers as Caps for the Design of Gated Silica Mesoporous Supports
A new hybrid material based on sulforhodamine-B dye-loaded silica mesoporous nanoparticles capped with a self-immolative gate has been synthesized and characterized. The gated material's controlled release behavior is monitored under different pH conditions. Under acidic and neutral conditions, a low level of dye release is detected. However, at slightly basic pH, significant dye release occurs owing to deprotonation of the phenol moiety in the capping molecule, which results in its disassembly.We thank MINECO/FEDER (MAT2015-64139-C4-1-R and MAT2015-64139-C4-4-R) and Generalitat Valenciana (PROMETEOII/2014/047) for support. SCSIE (Universidad de Valencia) is gratefully acknowledged for all the equipment employed.Juarez, LA.; Añón, E.; Giménez Morales, C.; Sancenón Galarza, F.; Martínez-Máñez, R.; Costero Nieto, AM.; Gaviña, P.... (2016). Self-Immolative Linkers as Caps for the Design of Gated Silica Mesoporous Supports. Chemistry - A European Journal. 22(40):14126-14130. https://doi.org/10.1002/chem.201602126S1412614130224