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[EN] Excessive apoptotic cell death is at the origin of several pathologies, such as degenerative disorders, stroke or ischemia-reperfusion damage. In this context, strategies to improve inhibition of apoptosis and other types of cell death are of interest and may represent a pharmacological opportunity for the treatment of cell-death-related disorders. In this scenario new peptide-containing delivery systems (solids S1-P1and S1-P2) are described based on meso-porous silica nanoparticles (MSNs) loaded with a dye and capped with the KKGDEVDKKARDEVDK (P1) peptide that contains two repeats of the DEVD target sequence that are selectively hydrolyzed by caspase3 (C3). This enzyme plays a central role in the execution-phase of apoptosis. HeLa cells electroporated with S1 P1are able to deliver the cargo in the presence of staurosporin (STS), which induces apoptosis with the consequent activation of the cytoplasmic C3 enzyme. Moreover, the nanoparticles S1-P2,containing both a cell-penetrating TAT peptide and P1 also entered in HeLa cells and delivered the cargo preferentially in cells treated with the apoptosis inducer cisplatin. ; We thank the Spanish Government (Project MAT2012-38429-C04 and SAF2010-15512) and the Generalitat Valenciana (PROMETEOII/2014/061) for support. C.T. is grateful to the Spanish Ministry of Science and Innovation for her PhD fellowship. L.M. thanks the Generalitat Valenciana (VALI+D program), Nice city council ("Aides Individuelles aux Jeunes Chercheurs - 2011") and Fondation de la Recherche Medicale for her postdoctoral contracts. C.C. thanks the Generalitat Valenciana for their postdoctoral contract VALI+D. We thank the confocal microscopy service, Alberto Hernandez from CIPF confocal microscopy service for their technical support. ; De La Torre Paredes, C.; Mondragón Martínez, L.; Coll Merino, MC.; García-Fernández, A.; Sancenón Galarza, F.; Martínez-Máñez, R.; Amorós, P. (2015). Caspase 3 Targeted Cargo Delivery in Apoptotic Cells Using Capped Mesoporous Silica Nanoparticles. Chemistry - A ...

Trapped: Mesoporous silica nanoparticles were loaded with a fluorescent guest and functionalized with octadecyltrimethoxysilane. The alkyl chains interact with paraffins, which build a hydrophobic layer around the particle (see picture). Upon melting of the paraffin, the guest molecule is released, as demonstrated in cells for the guest doxorubicin. The release temperature can be tuned by choosing an appropriate paraffin. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. ; Financial support from the Spanish Government (projects MAT2009-14564-C04-01 and SAF2010-15512) and the Generalitat Valenciana (projects PROMETEO/2009/016 and PROMETEO/2010/005) is gratefully acknowledged. L. M. thanks the Generalitat Valenciana for a VALi + d postdoctoral contract. We thank UPV electron microscopy and CIPF confocal microscopy services for technical support. ; Aznar Gimeno, E.; Mondragón Martínez, L.; Ros-Lis, JV.; Sancenón Galarza, F.; Marcos Martínez, MD.; Martínez Mañez, R.; Soto Camino, J. (2011). Finely tuned temperature-controlled cargo release using paraffin-capped mesoporous silica nanoparticles. Angewandte Chemie International Edition. (50):11172-11175. https://doi.org/10.1002/anie.201102756 ; S ; 11172 ; 11175 ; 50

11172 11175 50 ; S ; Trapped: Mesoporous silica nanoparticles were loaded with a fluorescent guest and functionalized with octadecyltrimethoxysilane. The alkyl chains interact with paraffins, which build a hydrophobic layer around the particle (see picture). Upon melting of the paraffin, the guest molecule is released, as demonstrated in cells for the guest doxorubicin. The release temperature can be tuned by choosing an appropriate paraffin. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. Financial support from the Spanish Government (projects MAT2009-14564-C04-01 and SAF2010-15512) and the Generalitat Valenciana (projects PROMETEO/2009/016 and PROMETEO/2010/005) is gratefully acknowledged. L. M. thanks the Generalitat Valenciana for a VALi + d postdoctoral contract. We thank UPV electron microscopy and CIPF confocal microscopy services for technical support. Aznar Gimeno, E.; Mondragón Martínez, L.; Ros-Lis, JV.; Sancenón Galarza, F.; Marcos Martínez, MD.; Martínez Mañez, R.; Soto Camino, J. (2011). Finely tuned temperature-controlled cargo release using paraffin-capped mesoporous silica nanoparticles. Angewandte Chemie International Edition. (50):11172-11175. https://doi.org/10.1002/anie.201102756

[EN] Trapped: Mesoporous silica nanoparticles were loaded with a fluorescent guest and functionalized with octadecyltrimethoxysilane. The alkyl chains interact with paraffins, which build a hydrophobic layer around the particle (see picture). Upon melting of the paraffin, the guest molecule is released, as demonstrated in cells for the guest doxorubicin. The release temperature can be tuned by choosing an appropriate paraffin. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. ; Financial support from the Spanish Government (projects MAT2009-14564-C04-01 and SAF2010-15512) and the Generalitat Valenciana (projects PROMETEO/2009/016 and PROMETEO/2010/005) is gratefully acknowledged. L.M. thanks the Generalitat Valenciana for a VALi+d postdoctoral contract. We thank UPV electron microscopy and CIPF confocal microscopy services for technical support. ; Aznar Gimeno, E.; Mondragón Martínez, L.; Ros-Lis, JV.; Sancenón Galarza, F.; Marcos Martínez, MD.; Martínez Mañez, R.; Soto Camino, J. (2011). Finely Tuned Temperature-Controlled Cargo Release Using Paraffin-Capped Mesoporous Silica Nanoparticles. ANGEW CHEM. 123(47):11368-11371. https://doi.org/10.1002/ange.201102756 ; S ; 11368 ; 11371 ; 123 ; 47

We thank the Spanish Government (project MAT2009-14564-C04 and CTQ2007-64735-AR07) the Generalitat Valencia (project PROMETEO/2009/016) for support. A.A. and L.M. thank the Generalitat Valenciana for their Santiago Grisolia Fellowship and VALI+D postdoctoral contract, respectively. We thank the confocal microscopy service from CIPF for technical support. ; Agostini, A.; Mondragón Martínez, L.; Coll Merino, MC.; Aznar Gimeno, E.; Marcos Martínez, MD.; Martínez Mañez, R.; Sancenón Galarza, F. (2012). Dual enzyme-triggered controlled release on capped nanometric silica mesoporous supports. ChemistryOpen. 1:17-20. https://doi.org/10.1002/open.201200003 ; S ; 17 ; 20 ; 1 ; Saha, S., Leung, K. C.-F., Nguyen, T. D., Stoddart, J. F., & Zink, J. I. (2007). Nanovalves. Advanced Functional Materials, 17(5), 685-693. doi:10.1002/adfm.200600989 ; Trewyn, B. G., Slowing, I. I., Giri, S., Chen, H.-T., & Lin, V. S.-Y. (2007). Synthesis and Functionalization of a Mesoporous Silica Nanoparticle Based on the Sol–Gel Process and Applications in Controlled Release. Accounts of Chemical Research, 40(9), 846-853. doi:10.1021/ar600032u ; Aznar, 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:10.1517/17425240902895980 ; Beck, J. S., Vartuli, J. C., Roth, W. J., Leonowicz, M. E., Kresge, C. T., Schmitt, K. D., … Schlenker, J. L. (1992). A new family of mesoporous molecular sieves prepared with liquid crystal templates. Journal of the American Chemical Society, 114(27), 10834-10843. doi:10.1021/ja00053a020 ; Wight, A. P., & Davis, M. E. (2002). Design and Preparation of Organic−Inorganic Hybrid Catalysts. Chemical Reviews, 102(10), 3589-3614. doi:10.1021/cr010334m ; Kickelbick, G. (2004). Mesoporöse anorganisch-organische Hybridmaterialien. Angewandte Chemie, 116(24), 3164-3166. doi:10.1002/ange.200301751 ; Kickelbick, G. (2004). Hybrid Inorganic–Organic Mesoporous Materials. Angewandte Chemie ...

MCM-41 silica nanoparticles were used as inorganic scaffolding to prepare a nanoscopic-capped hybrid material S1, which was able to release an entrapped cargo in the presence of certain enzymes, whereas in the absence of enzymes, a zero release system was obtained. S1 was prepared by loading nanoparticles with Safranine O dye and was then capped with a gluconamide derivative. In the absence of enzymes, the release of the dye from the aqueous suspensions of S1 was inhibited as a result of the steric hindrance imposed by the bulky gluconamide derivative, the polymerized gluconamide layer and the formation of a dense hydrogen-bonded network around the pore outlets. Upon the addition of amidase and pronase enzymes, delivery of Safranine O dye was observed due to the enzymatic hydrolysis of the amide bond in the anchored gluconamide derivative. S1 nanoparticles were not toxic for cells, as demonstrated by cell viability assays using HeLa and MCF-7 cell lines, and were associated with lysosomes, as shown by confocal microscopy. Finally, the S1¿CPT material loaded with the cytotoxic drug camptothecin and capped with the gluconamide derivative was prepared. The HeLa cells treated with S1¿CPT underwent cell death as a result of material internalization, and of the subsequent cellular enzyme-mediated hydrolysis and aperture of the molecular gate, which induced the release of the camptothecin cargo. ; We thank the Spanish Government (Project MAT2009-14564-C04 and SAF2010-15512) and the Generalitat Valenciana (Project PROMETEO/2009/016and/2010/005) for support. I. C. thanks the Universitat Politecnica de Valencia for her fellowship. L. M. thanks the Generalitat Valenciana for her post-doctoral VALi+d contract. E. A. and C. T. also thank the CIBER-BBN for contracts. We thank Eva Maria Lafuente Villarreal and Alberto Hernandez Cano from the Confocal Microscopy service of CIPF and the Electronic Microscopy service of UPV for their technical support. ; Candel Busquets, I.; Aznar Gimeno, E.; Mondragón Martínez, L.; De La Torre ...