Antibody-Capped Mesoporous Nanoscopic Materials:Design of a Probe for the Selective Chromo-FluorogenicDetection of Finasteride

[EN] The synthesis of capped mesoporous silica nanoparticles (MSN) conjugated with an antibody (AB) as a gatekeeper has been carried out in order to obtain a delivery system able to release an entrapped cargo (dye) in the presence of a target molecule (antigen) to which the conjugated antibody binds selectively. In particular, MSN loaded with rhodamine B and functionalized on the external surface with a suitable derivative of N-(t-butyl)- 3-oxo-(5a,17b)-4-aza-androst-1-ene-17-carboxamide (finasteride) have been prepared (S1). The addition of polyclonal antibodies against finasteride induced capping of the pores due to the interaction with the anchored hapten-like finasteride derivative to give a MSN¿hapten¿AB nanoparticle S1-AB. It was found that the addition of capped material S1-AB to water solutions containing finasteride resulted in displacement of the antibody, pore uncapping and entrapped-dye release. The response of the gated material is highly selective, and only finasteride, among other steroids, was able to induce a significant uncapping process. Compared with finasteride, the finasteride metabolite was able to release 17% of the dye, whereas the exogen steroids testosterone, metenolone and 16-b-hydroxystanozolol only induced very little release of rhodamine B (lower than 10%) from aqueous suspensions containing sensing solid S1-AB. A detection limit as low as 20 ppb was found for the fluorimetric detection of finasteride. In order to evaluate a possible application of the material for label-free detection of finasteride, the capped material was isolated and stored to give final sensing solid S1-AB-i. It was found to display a similar behavior towards finasteride as to that shown by freshly prepared S1-AB; even after a period of two months, no significant loss of selectivity or sensitivity was noted. Moreover, to study the application for the detection of finasteride in biological samples, this ¿aged¿ material, S1-AB-i, was tested using commercially available blank urine as matrix. Samples containing 70 and 90% blank urine were spiked with a defined amount of finasteride, and the concentration was determined using capped S1-AB-i. Recovery ranges from 94% to 118% were reached.Financial support from the Spanish Government (project MAT2009-14564-C04-01) and the Generalitat Valenciana (Spain) (projects PROMETEO/2009/016 and PROMETEO/2010/008) is gratefully acknowledged. E. C. thanks the Minesterio de Ciencia e Innovacion (MICINN, Spain) for her fellowship.Climent Terol, E.; Martínez Mañez, R.; Maquieira Catala, Á.; Sancenón Galarza, F.; Marcos Martínez, MD.; Brun Sánchez, EM.; Soto Camino, J.... (2012). Antibody-Capped Mesoporous Nanoscopic Materials:Design of a Probe for the Selective Chromo-FluorogenicDetection of Finasteride. ChemistryOpen. 1:251-259. https://doi.org/10.1002/open.201100008S251259

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

Encapsulation of folic acid in different silica porous supports: A comparative study

Although folic acid is essential to numerous bodily functions, recent research indicates that a massive exposition to the vitamin could be a double-edged sword. In this study, the capacity of different caped mesoporous silica particles (i.e. Hollow Silica Shells, MCM-41, SBA-15 and UVM-7) to dose FA during its passage through the gastrointestinal tract has been evaluated. Results confirmed that the four capped materials were capable to hinder the delivery of FA at low pH (i.e. stomach) as well as able to deliver great amounts of the vitamin at neutral pH (i.e. intestine). Nevertheless, the encapsulation efficiency and the deliver kinetics differed among supports. While supports with large pore entrance exhibited an initial fast release, MCM-41, showed a sustained release along the time. This correlation between textural properties and release kinetics for each of the supports reveals the importance of a proper support selection as a strategy to control the delivery of active molecules.Authors gratefully acknowledge the financial support from the Ministerio de Economia y Competitividad (Projects AGL2012-39597-C02-01, AGL2012-39597-C02-02 and MAT2012-38429-C04-01) and the Generalitat Valenciana (project PROMETEO/2009/016). E.P. and M.R. are grateful to the Ministerio de Ciencia e Innovacion for their Grants (AP2008-00620, AP2010-4369). Electron Microscopy Service of the UPV is also acknowledged.Pérez-Esteve, É.; Ruiz Rico, M.; De La Torre Paredes, C.; Villaescusa Alonso, LA.; Sancenón Galarza, F.; Marcos Martínez, MD.; Amoros Del Toro, PJ.... (2016). Encapsulation of folic acid in different silica porous supports: A comparative study. Food Chemistry. 196:66-75. https://doi.org/10.1016/j.foodchem.2015.09.017S667519

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

Fluorogenic detection of Tetryl and TNT explosives using nanoscopic-capped mesoporous hybrid materials

[EN] A hybrid capped mesoporous material, which was selectively opened in the presence of Tetryl and TNT, has been synthesised and used for the fluorogenic recognition of these nitroaromatic explosives.Financial support from the Spanish Government (project MAT2012-38429-C04-01) and the Generalitat Valencia (project PROMETEO/2009/016) is gratefully acknowledged. Y.S. and E.P. are grateful to the Spanish Ministry of Science and Innovation for their grants. A. A. also thanks the Generalitat Valenciana for his Santiago Grisolia fellowship.Salinas Soler, Y.; Agostini, A.; Pérez Esteve, E.; Martínez Mañez, R.; Sancenón Galarza, F.; Marcos Martínez, MD.; Soto Camino, J.... (2013). Fluorogenic detection of Tetryl and TNT explosives using nanoscopic-capped mesoporous hybrid materials. Journal of Materials Chemistry. 1(11):3561-3564. https://doi.org/10.1039/C3TA01438JS35613564111Singh, S. (2007). Sensors—An effective approach for the detection of explosives. Journal of Hazardous Materials, 144(1-2), 15-28. doi:10.1016/j.jhazmat.2007.02.018Schulte-Ladbeck, R., Vogel, M., & Karst, U. (2006). Recent methods for the determination of peroxide-based explosives. Analytical and Bioanalytical Chemistry, 386(3), 559-565. doi:10.1007/s00216-006-0579-ySmith, R. G., D’Souza, N., & Nicklin, S. (2008). A review of biosensors and biologically-inspired systems for explosives detection. The Analyst, 133(5), 571. doi:10.1039/b717933mMoore, D. S. (2004). Instrumentation for trace detection of high explosives. Review of Scientific Instruments, 75(8), 2499-2512. doi:10.1063/1.1771493H�kansson, K., Coorey, R. V., Zubarev, R. A., Talrose, V. L., & H�kansson, P. (2000). Low-mass ions observed in plasma desorption mass spectrometry of high explosives. Journal of Mass Spectrometry, 35(3), 337-346. doi:10.1002/(sici)1096-9888(200003)35:33.0.co;2-7Wallis, E., Griffin, T. M., Popkie, Jr., N., Eagan, M. A., McAtee, R. F., Vrazel, D., & McKinly, J. (2005). Instrument response measurements of ion mobility spectrometers in situ: maintaining optimal system performance of fielded systems. Chemical and Biological Sensing VI. doi:10.1117/12.609920Germain, M. E., & Knapp, M. J. (2009). Optical explosives detection: from color changes to fluorescence turn-on. Chemical Society Reviews, 38(9), 2543. doi:10.1039/b809631gForzani, E. S., Lu, D., Leright, M. J., Aguilar, A. D., Tsow, F., Iglesias, R. A., … Tao, N. (2009). A Hybrid Electrochemical−Colorimetric Sensing Platform for Detection of Explosives. Journal of the American Chemical Society, 131(4), 1390-1391. doi:10.1021/ja809104hSalinas, Y., Martínez-Máñez, R., Marcos, M. D., Sancenón, F., Costero, A. M., Parra, M., & Gil, S. (2012). Optical chemosensors and reagents to detect explosives. Chem. Soc. Rev., 41(3), 1261-1296. doi:10.1039/c1cs15173hThomas, S. W., Joly, G. D., & Swager, T. M. (2007). Chemical Sensors Based on Amplifying Fluorescent Conjugated Polymers. Chemical Reviews, 107(4), 1339-1386. doi:10.1021/cr0501339Gao, D., Wang, Z., Liu, B., Ni, L., Wu, M., & Zhang, Z. (2008). Resonance Energy Transfer-Amplifying Fluorescence Quenching at the Surface of Silica Nanoparticles toward Ultrasensitive Detection of TNT. Analytical Chemistry, 80(22), 8545-8553. doi:10.1021/ac8014356Zhang, S., Lü, F., Gao, L., Ding, L., & Fang, Y. (2007). Fluorescent Sensors for Nitroaromatic Compounds Based on Monolayer Assembly of Polycyclic Aromatics. Langmuir, 23(3), 1584-1590. doi:10.1021/la062773sHughes, A. D., Glenn, I. C., Patrick, A. D., Ellington, A., & Anslyn, E. V. (2008). A Pattern Recognition Based Fluorescence Quenching Assay for the Detection and Identification of Nitrated Explosive Analytes. Chemistry - A European Journal, 14(6), 1822-1827. doi:10.1002/chem.200701546Vijayakumar, C., Tobin, G., Schmitt, W., Kim, M.-J., & Takeuchi, M. (2010). Detection of explosive vapors with a charge transfer molecule: self-assembly assisted morphology tuning and enhancement in sensing efficiency. Chemical Communications, 46(6), 874. doi:10.1039/b921520dSalinas, Y., Climent, E., Martínez-Máñez, R., Sancenón, F., Marcos, M. D., Soto, J., … Pérez de Diego, A. (2011). Highly selective and sensitive chromo-fluorogenic detection of the Tetryl explosive using functional silica nanoparticles. Chemical Communications, 47(43), 11885. doi:10.1039/c1cc14877jCliment, 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., Marcos, M. D., Martínez-Máñez, R., Sancenón, F., Soto, J., Rurack, K., & Amorós, P. (2009). The Determination of Methylmercury in Real Samples Using Organically Capped Mesoporous Inorganic Materials Capable of Signal Amplification. Angewandte Chemie International Edition, 48(45), 8519-8522. doi:10.1002/anie.200904243Climent, 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/ja904456dCabrera, S., El Haskouri, J., Guillem, C., Latorre, J., Beltrán-Porter, A., Beltrán-Porter, D., … Amorós *, P. (2000). Generalised syntheses of ordered mesoporous oxides: the atrane route. Solid State Sciences, 2(4), 405-420. doi:10.1016/s1293-2558(00)00152-7Kolb, H. C., Finn, M. G., & Sharpless, K. B. (2001). Click Chemistry: Diverse Chemical Function from a Few Good Reactions. Angewandte Chemie International Edition, 40(11), 2004-2021. doi:10.1002/1521-3773(20010601)40:113.0.co;2-5Felix, F., Ferguson, J., Guedel, H. U., & Ludi, A. (1980). The electronic spectrum of tris(2,2’-bipyridine)ruthenium(2+). Journal of the American Chemical Society, 102(12), 4096-4102. doi:10.1021/ja00532a019Lytle, F. E., & Hercules, D. M. (1969). Luminescence of tris(2,2’-bipyridine)ruthenium(II) dichloride. Journal of the American Chemical Society, 91(2), 253-257. doi:10.1021/ja01030a00

Oligonucleotide-capped mesoporous silica nanoparticles as DNA-responsive dye delivery systems for genomic DNA detection

[EN] New hybrid oligonucleotide-capped mesoporous silica nanoparticles able to detect genomic DNA were designed.Financial support from the Spanish Government (Project MAT2012-38429-C04) and the Generalitat Valencia (Project PROMETEOII/2014/047) is gratefully acknowledged. Ll. P. is grateful to the Universidad Politecnica de Valencia for his grant.Pascual Vidal, L.; Baroja, I.; Aznar Gimeno, E.; Sancenón Galarza, F.; Marcos Martínez, MD.; Murguía Ibáñez, JR.; Amoros Del Toro, PJ.... (2015). Oligonucleotide-capped mesoporous silica nanoparticles as DNA-responsive dye delivery systems for genomic DNA detection. Chemical Communications. 51(8):1414-1416. https://doi.org/10.1039/C4CC08306GS14141416518Agostini, 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.201204663Zhang, Q., Wang, X., Li, P.-Z., Nguyen, K. T., Wang, X.-J., Luo, Z., … Zhao, Y. (2013). Biocompatible, Uniform, and Redispersible Mesoporous Silica Nanoparticles for Cancer-Targeted Drug Delivery In Vivo. Advanced Functional Materials, 24(17), 2450-2461. doi:10.1002/adfm.201302988Chen, C., Geng, J., Pu, F., Yang, X., Ren, J., & Qu, X. (2010). Polyvalent Nucleic Acid/Mesoporous Silica Nanoparticle Conjugates: Dual Stimuli-Responsive Vehicles for Intracellular Drug Delivery. Angewandte Chemie International Edition, 50(4), 882-886. doi:10.1002/anie.201005471Zhou, L., Chen, Z., Dong, K., Yin, M., Ren, J., & Qu, X. (2013). DNA-mediated Construction of Hollow Upconversion Nanoparticles for Protein Harvesting and Near-Infrared Light Triggered Release. Advanced Materials, 26(15), 2424-2430. doi:10.1002/adma.201304437Agostini, 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/la303161eColl, 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/ar3001469Climent, E., Martínez-Máñez, R., Maquieira, Á., Sancenón, F., Marcos, M. D., Brun, E. M., … Amorós, P. (2012). Antibody-Capped Mesoporous Nanoscopic Materials: Design of a Probe for the Selective Chromo-Fluorogenic Detection of Finasteride. ChemistryOpen, 1(6), 251-259. doi:10.1002/open.201100008Oroval, M., Climent, E., Coll, C., Eritja, R., Aviñó, A., Marcos, M. D., … Amorós, P. (2013). An aptamer-gated silica mesoporous material for thrombin detection. Chemical Communications, 49(48), 5480. doi:10.1039/c3cc42157kChen, M., Huang, C., He, C., Zhu, W., Xu, Y., & Lu, Y. (2012). A glucose-responsive controlled release system using glucose oxidase-gated mesoporous silica nanocontainers. Chemical Communications, 48(76), 9522. doi:10.1039/c2cc34290aCliment, 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., Mondragón, L., Martínez-Máñez, R., Sancenón, F., Marcos, M. D., Murguía, J. R., … Pérez-Payá, E. (2013). Selective, Highly Sensitive, and Rapid Detection of Genomic DNA by Using Gated Materials:MycoplasmaDetection. Angewandte Chemie International Edition, 52(34), 8938-8942. doi:10.1002/anie.201302954Zhang, Z., Balogh, D., Wang, F., Sung, S. Y., Nechushtai, R., & Willner, I. (2013). Biocatalytic Release of an Anticancer Drug from Nucleic-Acids-Capped Mesoporous SiO2 Using DNA or Molecular Biomarkers as Triggering Stimuli. ACS Nano, 7(10), 8455-8468. doi:10.1021/nn403772jWu, L., Ren, J., & Qu, X. (2014). Target-responsive DNA-capped nanocontainer used for fabricating universal detector and performing logic operations. Nucleic Acids Research, 42(21), e160-e160. doi:10.1093/nar/gku858Drexler, H. G., & Uphoff, C. C. (2002). Cytotechnology, 39(2), 75-90. doi:10.1023/a:1022913015916Matas Andreu, L., Molinos Abós, S., Fernández Rivas, G., González Soler, V., & Ausina Ruiz, V. (2006). Diagnóstico serológico de las infecciones por Mycoplasma pneumoniae. Enfermedades Infecciosas y Microbiología Clínica, 24, 19-23. doi:10.1157/13094274V. Ausina , Infecciones causadas por micoplasmas, Medicina Interna, Elsevier España, 2004, 15th edn, pp. 2363–236

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

Enhanced antifungal efficacy of tebuconazole using gated pH-driven mesoporous nanoparticles

pH-sensitive gated mesoporous silica nanoparticles have been synthesized. Increased extracellular pH and internalization into living yeast cells triggered molecular gate aperture and cargo release. Proper performance of the system was demonstrated with nanodevices loaded with fluorescein or with the antifungal agent tebuconazole. Interestingly, nanodevices loaded with tebuconazole significantly enhanced tebuconazole cytotoxicity. As alterations of acidic external pH are a key parameter in the onset of fungal vaginitis, this nanodevice could improve the treatment for vaginal mycoses.Mas Font, N.; Galiana, I.; Hurtado, S.; Mondragón Martínez, L.; Bernardos Bau, A.; Sancenón Galarza, F.; Marcos Martínez, MD.... (2014). Enhanced antifungal efficacy of tebuconazole using gated pH-driven mesoporous nanoparticles. International Journal of Nanomedicine. 9:2597-2606. doi:10.2147/IJN.S59654S25972606

Organic-Inorganic Hybrid Mesoporous Materials as Regenerable Sensing Systems for the Recognition of Nitroaromatic Explosives

[EN] Fluorescent organic-inorganic mesoporous hybrid materials have been prepared and characterised, and their behaviour against nitroaromatic explosives have been tested. MCM-41 silica was used as an inorganic scaffold and pyrene (P derivative containing trialkoxysilane moieties), dansyl and fluorescein (D and F derivatives also containing trialkoxysilane groups, respectively) fluorophores have been anchored on hybrid materials by a co-condensation method to obtain a homogenous distribution of dyes into the pores of the support. Six sensing materials have been prepared, of which SP, SD, SF were hydrophilic and SPh, SDh, SFh were hydrophobic. Template-free hydrophilic materials (SP, SD, SF) were obtained after repeated NH4NO3/ethanol extractions under temperature from as-synthesised (MP, MD and MF supports, respectively) solids. Hydrophobic materials (SPh, SDh, SFh) were prepared by using excess 1,1,1,3,3,3-hexamethyldisilazane with template-free hydrophilic (SP, SD and SF) materials. The six final materials displayed the typical emission bands of the grafted fluorophores. In particular, SP and SPh show the typical pyrene monomer (370-420nm) and excimer (430-600nm) emissions. SD and SDh exhibit the broad dansyl fluorescence band in the 450-600nm range, whereas solids SF and SFh present sharp fluorescein emission centred at 525nm. The fluorescent behaviour of the six final materials was tested in the presence of explosives (pentaerythritol tetranitrate (PETN), hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX), nitrobenzene (NB), 1,3,5-trinitrobenzene (TNB), 2,4,6-trinitrotoluene (TNT), 2,4-dinitrotoluene (DNT), 2,4,6-trinitrophenylmethylnitramine (Tetryl) and picric acid (PA)). Only nitroaromatic compounds were able to induce emission quenching. As a general trend, the quenching degree depended on the nature of the final material. The best response was obtained with explosives PA and Tetryl, which were able to significantly quench the emission of the sensing supports. The observed quenching was ascribed to the - stacking interactions between the electron-donor fluorophores and the electron-withdrawing nitroaromatic explosives. When using SPh for Tetryl and PA, the limits of detection were 8.5 and 1.4ppm, respectively, whereas they were 14.4 and 1.2ppm for SDh. Principal component analysis algorithms were applied to the fluorescence measurements taken with the six hybrid materials and the seven explosives. The obtained score plot showed well-defined clusters for the seven explosives tested. Finally, solid SDh was applied to detect trace amounts of Tetryl in soil samples with good results.Financial support from the Spanish Government (Project MAT2012-38429-C04-01) and the Generalitat Valencia (Project PROMETEO/2009/016) is gratefully acknowledged. Y.S. is grateful to the Spanish Ministry of Science and Innovation for her grant. I. C is also grateful to the Universidad Politecnica de Valencia for her grant.Sarkar, K.; Salinas Soler, Y.; Campos Sánchez, I.; Martínez Mañez, R.; Marcos Martínez, MD.; Sancenón Galarza, F.; Amoros Del Toro, P. (2013). Organic-Inorganic Hybrid Mesoporous Materials as Regenerable Sensing Systems for the Recognition of Nitroaromatic Explosives. ChemPlusChem. 78(7):684-694. https://doi.org/10.1002/cplu.20130014068469478

Low-cost materials for boron adsorption from water

[EN] Knowing the affinity of boron aqueous species for cis-diol organic groups, five different hybrid materials have been prepared by anchoring glucose groups onto the surface of silica matrices with a different surface topology: UVM-7 bimodal mesoporous silica, UVM-11 unimodal non-templated mesoporous silica, commercial silica fume and two silica xerogels with pores within the mesoporous range (13-50 nm). After optimizing the experimental conditions, a comparison was made of the boron adsorption capacities in water. The relationship of the structural and functionalization parameters is discussed and the importance of the surface topology in the final adsorption behaviour is revealed. Hence, despite the UVM-7 based material being the best boron adsorbent, the solid based on one of the xerogels is seen to be a good candidate for preparing low-cost boron adsorbents.Financial support from the Spanish Government (Project MAT2009-14564-C04-01 and MAT2009-14564-C04-04) and the Generalitat Valenciana (Project PROMETEO/2009/016) is gratefully acknowledged. C. S. thanks the MICINN for a predoctoral fellowship.Sanfeliu Cano, C.; Martínez Mañez, R.; Sancenón Galarza, F.; Soto Camino, J.; Puchol, V.; Amoros Del Toro, P.; Marcos Martínez, MD. (2012). Low-cost materials for boron adsorption from water. Journal of Materials Chemistry. 22(48):25362-25372. https://doi.org/10.1039/C2JM32819DS2536225372224