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[EN] One appealing concept in the field of hybrid materials is related to the design of gated materials. These materials are prepared in such a way that the release of chemical or biochemical species from voids of porous supports to a solution is triggered upon the application of external stimuli. Such gated materials are mainly composed of two subunits: i) a porous inorganic scaffold in which a cargo is stored, and ii) certain molecular or supramolecular entities, grafted onto the external surface, that can control mass transport from the interior of the pores. On the basis of this concept, a large number of examples are developed in the past ten years. A comprehensive overview of gated materials used in drug delivery applications in in vivo models from 2016 to date is thus given here. ; The authors thank Spanish Government (Project No. RTI2018-100910-B-C41 (MCUI/AEI/FEDER, UE)) and Generalitat Valenciana (PROMETEO2018/024) for their support. ; García-Fernández, A.; Aznar, E.; Martínez-Máñez, R.; Sancenón Galarza, F. (2020). New Advances in In Vivo Applications of Gated Mesoporous Silica as Drug Delivery Nanocarriers. Small. 16(3):1-62. https://doi.org/10.1002/smll.201902242 ; S ; 1 ; 62 ; 16 ; 3 ; Tang, Q., Yu, B., Gao, L., Cong, H., Song, N., & Lu, C. (2018). Stimuli Responsive Nanoparticles for Controlled Anti-cancer Drug Release. Current Medicinal Chemistry, 25(16), 1837-1866. doi:10.2174/0929867325666180111095913 ; Aftab, S., Shah, A., Nadhman, A., Kurbanoglu, S., Aysıl Ozkan, S., Dionysiou, D. D., … Aminabhavi, T. M. (2018). Nanomedicine: An effective tool in cancer therapy. International Journal of Pharmaceutics, 540(1-2), 132-149. doi:10.1016/j.ijpharm.2018.02.007 ; Kozlovskaya, V., Xue, B., & Kharlampieva, E. (2016). Shape-Adaptable Polymeric Particles for Controlled Delivery. Macromolecules, 49(22), 8373-8386. doi:10.1021/acs.macromol.6b01740 ; Mishra, D. K., Shandilya, R., & Mishra, P. K. (2018). Lipid based nanocarriers: a translational perspective. Nanomedicine: Nanotechnology, Biology ...

[EN] A biocomputing strategy implemented in hybrid nanocarriers for controlled cargo delivery is described. The nanodevice consists of enzyme-functionalized Janus Au-mesoporous silica nanoparticles, which behave as an electronic demultiplexer (DEMUX). The nanocarrier is capable of reading molecular information from the environment (lactose) and selecting one of two possible outputs (galactose production or 4-methylumbellilferone release and activation) depending on the presence of an addressing input NAD(+). ; The authors wish to thank the Spanish Government (projects RTI2018-100910-B-C41 (MCUI/AEI/FEDER, UE), CTQ2017-87954-P), the Generalitat Valenciana (PROMETEO 2018/024), the Comunidad de Madrid (IND2017/BMD-7642) and CIBER-BBN (NANOCOMMUNITY project) for support. ; De Luis-Fernández, B.; García-Fernández, A.; Llopis-Lorente, A.; Villalonga, R.; Sancenón Galarza, F.; Martínez-Máñez, R. (2020). A 1-to-2 demultiplexer hybrid nanocarrier for cargo delivery and activation. Chemical Communications. 56(69):9974-9977. https://doi.org/10.1039/d0cc03803b ; S ; 9974 ; 9977 ; 56 ; 69 ; Soto, F., & Chrostowski, R. (2018). Frontiers of Medical Micro/Nanorobotics: in vivo Applications and Commercialization Perspectives Toward Clinical Uses. Frontiers in Bioengineering and Biotechnology, 6. doi:10.3389/fbioe.2018.00170 ; Zhang, X., Chen, L., Lim, K. H., Gonuguntla, S., Lim, K. W., Pranantyo, D., … Soh, S. (2019). The Pathway to Intelligence: Using Stimuli‐Responsive Materials as Building Blocks for Constructing Smart and Functional Systems. Advanced Materials, 31(11), 1804540. doi:10.1002/adma.201804540 ; Mailloux, S., & Katz, E. (2014). Biocomputing, Biosensing and Bioactuation Based on Enzyme Biocatalyzed Reactions. Biocatalysis, 1(1). doi:10.2478/boca-2014-0002 ; Katz, E. (2018). Boolean Logic Gates Realized with Enzyme‐catalyzed Reactions – Unusual Look at Usual Chemical Reactions. ChemPhysChem, 20(1), 9-22. doi:10.1002/cphc.201800900 ; Erbas-Cakmak, S., Kolemen, S., Sedgwick, A. C., Gunnlaugsson, T., James, T. ...

[EN] An increase of bone diseases incidence has boosted the study of ceramic biomaterials as potential osteo-inductive scaffolds. In particular, mesoporous bioactive glasses have demonstrated to possess a broad application in the bone regeneration field, due their osteo-regenerative capability and their ability to release drugs from the mesoporous structure. These special features have been studied as an option to fight against bone infection, which is one of the most common problems regarding bone regeneration therapies. In this work, a mesoporous bioglass functionalized with polyamines and capped with adenosine triphosphate (ATP) as the molecular gate was developed for the controlled release of the antibiotic levofloxacin. Phosphate bonds of ATP were hydrolyzed in the presence of acid phosphatase (APase), the concentration of which is significantly increased in bone infection due to the activation of bone resorption processes. The solid was characterized and tested successfully against bacteria. The final gated solid induced bacterial death only in the presence of acid phosphatase. Additionally, it was demonstrated that the solid is not toxic against human cells. The double function of the prepared material as a drug delivery system and bone regeneration enhancer confirms the possible development of a new approach in the tissue engineering field, in which controlled release of therapeutic agents can be finely tuned and, at the same time, osteoinduction is favored. ; The authors thank the Spanish Government for projects MAT2015-64139-C04-01-R, MAT2015-64831-R and MAT2016-75611-R (AEI/FEDER, UE). Generalitat Valenciana (project PROMETEOII/2014/047) and CIBER-BBN (project SPRING) are also acknowledged for their support. M.V.R. acknowledges funding from the European Research Council (Advanced Grant VERDI; ERC-2015-AdG Proposal 694160). L.P. thanks Universitat Politecnica de Valencia for her FPI grant. N.G.C. and A.G. thank to Ministerio de Ciencia e Innovacion and Ministerio de Educacion, Cultura y Deporte for ...

18944 18951 24 71 ; S ; Candel, I., Aznar, E., Mondragón, L., Torre, C. de la, Martínez-Máñez, R., Sancenón, F., … Parra, M. (2012). Amidase-responsive controlled release of antitumoral drug into intracellular media using gluconamide-capped mesoporous silica nanoparticles. Nanoscale, 4(22), 7237. doi:10.1039/c2nr32062b ; [EN] An increase of bone diseases incidence has boosted the study of ceramic biomaterials as potential osteo-inductive scaffolds. In particular, mesoporous bioactive glasses have demonstrated to possess a broad application in the bone regeneration field, due their osteo-regenerative capability and their ability to release drugs from the mesoporous structure. These special features have been studied as an option to fight against bone infection, which is one of the most common problems regarding bone regeneration therapies. In this work, a mesoporous bioglass functionalized with polyamines and capped with adenosine triphosphate (ATP) as the molecular gate was developed for the controlled release of the antibiotic levofloxacin. Phosphate bonds of ATP were hydrolyzed in the presence of acid phosphatase (APase), the concentration of which is significantly increased in bone infection due to the activation of bone resorption processes. The solid was characterized and tested successfully against bacteria. The final gated solid induced bacterial death only in the presence of acid phosphatase. Additionally, it was demonstrated that the solid is not toxic against human cells. The double function of the prepared material as a drug delivery system and bone regeneration enhancer confirms the possible development of a new approach in the tissue engineering field, in which controlled release of therapeutic agents can be finely tuned and, at the same time, osteoinduction is favored. The authors thank the Spanish Government for projects MAT2015-64139-C04-01-R, MAT2015-64831-R and MAT2016-75611-R (AEI/FEDER, UE). Generalitat Valenciana (project PROMETEOII/2014/047) and CIBER-BBN (project SPRING) are also ...

[EN] Mesoporous silica nanoparticles capped with acetylcholinesterase, through boronic ester linkages, selectively release an entrapped cargo in the presence of acetylcholine. ; The authors acknowledge financial support from the Spanish Government (MAT2015-64139-C4-1-R, MAT2015-64139-C4-4-R and AGL2015-70235-C2-2-R) and the Generalitat Valenciana (PROMETEO2018/024). T. Godoy-Reyes is grateful to Generalitat Valenciana for her Santiago Grisollía fellowship. A. García-Fernández is grateful to the Spanish Government for her FPU fellowship ; Godoy-Reyes, TM.; Llopis-Lorente, A.; García-Fernández, A.; Gaviña, P.; Costero, AM.; Martínez-Máñez, R.; Sancenón Galarza, F. (2019). Acetylcholine-responsive cargo release using acetylcholinesterase-capped nanomaterials. Chemical Communications. 55(41):5785-5788. https://doi.org/10.1039/c9cc02602a ; S ; 5785 ; 5788 ; 55 ; 41 ; McCorry, L. K. (2007). Physiology of the Autonomic Nervous System. American Journal of Pharmaceutical Education, 71(4), 78. doi:10.5688/aj710478 ; W. M. Haschek , C. G.Rousseaux and M. A.Wallig , Nervous System , in Fundamentals of Toxicologic Pathology , 2nd edn, Academic Press CY , San Diego , 2010 , p. 377 ; Klinkenberg, I., Sambeth, A., & Blokland, A. (2011). Acetylcholine and attention. Behavioural Brain Research, 221(2), 430-442. doi:10.1016/j.bbr.2010.11.033 ; Hasselmo, M. E. (2006). The role of acetylcholine in learning and memory. Current Opinion in Neurobiology, 16(6), 710-715. doi:10.1016/j.conb.2006.09.002 ; An, M. C., Lin, W., Yang, J., Dominguez, B., Padgett, D., Sugiura, Y., … Lee, K.-F. (2010). Acetylcholine negatively regulates development of the neuromuscular junction through distinct cellular mechanisms. Proceedings of the National Academy of Sciences, 107(23), 10702-10707. doi:10.1073/pnas.1004956107 ; Ehrenstein, G., Galdzicki, Z., & Lange, G. D. (1997). The choline-leakage hypothesis for the loss of acetylcholine in Alzheimer's disease. Biophysical Journal, 73(3), 1276-1280. doi:10.1016/s0006-3495(97)78160-8 ; Fambrough, D. ...

5785 5788 55 41 ; S ; Godoy-Reyes, TM.; Llopis-Lorente, A.; García-Fernández, A.; Gaviña, P.; Costero, AM.; Martínez-Máñez, R.; Sancenón Galarza, F. (2019). Acetylcholine-responsive cargo release using acetylcholinesterase-capped nanomaterials. Chemical Communications. 55(41):5785-5788. https://doi.org/10.1039/c9cc02602a Díez, P., Esteban-Fernández de Ávila, B., Ramírez-Herrera, D. E., Villalonga, R., & Wang, J. (2017). Biomedical nanomotors: efficient glucose-mediated insulin release. Nanoscale, 9(38), 14307-14311. doi:10.1039/c7nr05535h ; [EN] Mesoporous silica nanoparticles capped with acetylcholinesterase, through boronic ester linkages, selectively release an entrapped cargo in the presence of acetylcholine. The authors acknowledge financial support from the Spanish Government (MAT2015-64139-C4-1-R, MAT2015-64139-C4-4-R and AGL2015-70235-C2-2-R) and the Generalitat Valenciana (PROMETEO2018/024). T. Godoy-Reyes is grateful to Generalitat Valenciana for her Santiago Grisollía fellowship. A. García-Fernández is grateful to the Spanish Government for her FPU fellowship McCorry, L. K. (2007). Physiology of the Autonomic Nervous System. American Journal of Pharmaceutical Education, 71(4), 78. doi:10.5688/aj710478 W. M. Haschek , C. G.Rousseaux and M. A.Wallig , Nervous System , in Fundamentals of Toxicologic Pathology , 2nd edn, Academic Press CY , San Diego , 2010 , p. 377 Klinkenberg, I., Sambeth, A., & Blokland, A. (2011). Acetylcholine and attention. Behavioural Brain Research, 221(2), 430-442. doi:10.1016/j.bbr.2010.11.033 Hasselmo, M. E. (2006). The role of acetylcholine in learning and memory. Current Opinion in Neurobiology, 16(6), 710-715. doi:10.1016/j.conb.2006.09.002 An, M. C., Lin, W., Yang, J., Dominguez, B., Padgett, D., Sugiura, Y., … Lee, K.-F. (2010). Acetylcholine negatively regulates development of the neuromuscular junction through distinct cellular mechanisms. Proceedings of the National Academy of Sciences, 107(23), 10702-10707. doi:10.1073/pnas.1004956107 Ehrenstein, G., Galdzicki, ...

[EN] Here, we present the design of smart nano-devices capable of reading molecular information from the environment and acting accordingly by processing Boolean logic tasks. As proof of concept, we prepared Au-mesoporous silica (MS) nanoparticles functionalized with the enzyme glucose dehydrogenase (GDH) on the Au surface and with supramolecular nanovalves as caps on the MS surface, which is loaded with a cargo (dye or drug). The nanodevice acts as an AND logic gate and reads information from the solution (presence of glucose and nicotinamide adenine dinucleotide (NADI), which results in cargo release. We show the possibility of coimmobilizing GDH and the enzyme urease on nanoparticles to mimic an INHIBIT logic gate, in which the AND gate is switched off by the presence of urea. We also show that such nanodevices can deliver cytotoxic drugs in cancer cells by recognizing intracellular NAD(+) and the presence of glucose. ; A.L.-L. is grateful to "La Caixa" Banking Foundation for his Ph.D. grant. A.G.-F. and B.de L. thank the Spanish government for FPU fellowships. The authors are grateful to the Spanish Government (MINECO Projects MAT2015-64139-C4-1, CTQ2014-58989-P, and CTQ2015-71936-REDT) and the Generalitat Valencia (Project PROMETEOII/2014/047 and PROMETEOII/2014/061) for support. The Comunidad de Madrid (S2013/MIT-3029, Programme NANOAVANSENS) is also gratefully acknowledged. ; Llopis-Lorente, A.; De Luis-Fernández, B.; García-Fernández, A.; Jiménez-Falcao, S.; Orzaez, M.; Sancenón Galarza, F.; Villalonga, R. (2018). Hybrid Mesoporous Nanocarriers Act by Processing Logic Tasks: Toward the Design of Nanobots Capable of Reading Information from the Environment. ACS Applied Materials & Interfaces. 10(31):26494-26500. https://doi.org/10.1021/acsami.8b05920 ; S ; 26494 ; 26500 ; 10 ; 31

This is the peer reviewed version of the following article: B. Lozano-Torres, J. F. Blandez, I. Galiana, A. García-Fernández, M. Alfonso, M. D. Marcos, M. Orzáez, F. Sancenón, R. Martínez-Máñez, Angew. Chem. Int. Ed. 2020, 59, 15152., which has been published in final form at https://doi.org/10.1002/anie.202004142. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving. ; [EN] In vivo detection of cellular senescence is accomplished by using mesoporous silica nanoparticles loaded with the NIR-FDA approved Nile blue (NB) dye and capped with a galactohexasaccharide (S3). NB emission at 672 nm is highly quenched inside S3, yet a remarkable emission enhancement is observed upon cap hydrolysis in the presence of beta-galactosidase and dye release. The efficacy of the probe to detect cellular senescence is tested in vitro in melanoma SK-Mel-103 and breast cancer 4T1 cells and in vivo in palbociclib-treated BALB/cByJ mice bearing breast cancer tumor. ; R.M. thanks financial support from the Spanish Government (RTI2018-100910-B-C41 and RTI2018-101599-B-C22 (MCUI/AEI/FEDER, UE)) and the Generalitat Valenciana (PROMETEO 2018/024). M.O. thanks the financial support from SAF2017-84689-R project and MINECO/AEI/FEDER, UE and the Generalitat Valenciana (PROMETEO/2019/065). B.L.-T. is grateful to the Spanish Ministry of Economy for her PhD grant. I.G. thanks her contract from IDM. J.F.-B. and M.A. thank the UPV for their postdoctoral fellowship. ; Lozano-Torres, B.; Blandez, JF.; Galiana, I.; García-Fernández, A.; Alfonso-Navarro, M.; Marcos Martínez, MD.; Orzáez, M. (2020). Real-Time In Vivo Detection of Cellular Senescence through the Controlled Release of the NIR Fluorescent Dye Nile Blue. Angewandte Chemie International Edition. 59(35):15152-15156. https://doi.org/10.1002/anie.202004142 ; S ; 15152 ; 15156 ; 59 ; 35 ; He, S., & Sharpless, N. E. (2017). Senescence in Health and Disease. Cell, 169(6), 1000-1011. doi:10.1016/j.cell.2017.05.015 ; Lozano-Torres, ...

[EN] We report a delivery system based on Au-mesoporous silica (MS) nanoparticles functionalized with acetylcholinesterase on the Au face as a control unit and with disulfide-containing oligo(ethylene glycol) chains on the MS face as caps. The control unit handles the chemical information in the environment (the presence of acetyl-thiocholine or enzyme inhibitors) that results in a tuned cargo delivery from the nanocarrier. The nanodevice displayed an enhanced cargo delivery in cancer cells (safranin O and doxorubicin) in the presence of acetylthiocholine. ; A. Llopis-Lorente thanks "La Caixa" Banking Foundation for his PhD fellowship. A. Garcia-Fernandez is grateful to the Spanish government for an FPU grant. The authors are grateful to the Spanish Government (MINECO Projects MAT2015-64139-C4-1, CTQ2014-58989-P and CTQ2015-71936-REDT) and the Generalitat Valencia (Project PROMETEOII/2014/047) for support. The Comunidad de Madrid (S2013/MIT-3029, Programme NANOAVANSENS) is also gratefully acknowledged. ; Llopis-Lorente, A.; De Luis-Fernández, B.; García-Fernández, A.; Diez, P.; Sánchez, A.; Marcos Martínez, MD.; Villalonga, R. (2017). Au-Mesoporous silica nanoparticles gated with disulfide-linked oligo(ethylene glycol) chains for tunable cargo delivery mediated by an integrated enzymatic control unit. Journal of Materials Chemistry B. 5(33):6734-6739. https://doi.org/10.1039/c7tb02045g ; S ; 6734 ; 6739 ; 5 ; 33

[EN] Mucin 1 (MUC1) is a cell surface protein overexpressed in breast cancer. Mesoporous silica nanoparticles (MSNs) loaded with safranin O, functionalized with aminopropyl groups and gated with the negatively charged MUC1 aptamer have been prepared (S1-apMUC1) for specific targeting and cargo release in tumoral versus non-tumoral cells. Confocal microscopy studies showed that the S1-apMUC1 nanoparticles were internalized in MDA-MB-231 breast cancer cells that overexpress MUC1 receptor with subsequent pore opening and cargo release. Interestingly, the MCF-10-A non-tumorigenic breast epithelial cell line that do not overexpress MUC1, showed reduced (S1-apMUC1) internalization. Negligible internalization was also found for S1-ap nanoparticles that contained a scrambled DNA sequence as gatekeeper. S2-apMUC1 nanoparticles (similar to S1-apMUC1 but loaded with doxorubicin) internalized in MDA-MB-231 cells and induced a remarkable reduction in cell viability. Moreover, S1-apMUC1 nanoparticles radio-labeled with Tc-99m (S1-apMUC1-Tc) showed a remarkable tumor targeting in in vivo studies with MDA-MB-231 tumor-bearing Balb/c mice. (C) 2017 Elsevier Inc. All rights reserved. ; Financial support from the Spanish Government and FEDER funds (Project MAT2015-64139-C4-1) and the Generalitat Valenciana (Project PROMETEOII/2014/047) is gratefully acknowledged. ; Pascual, L.; Cerqueira, C.; García-Fernández, A.; De Luis-Fernández, B.; Soares, E.; Souza, M.; Missailidis, S. (2017). MUC1 aptamer-capped mesoporous silica nanoparticles for controlled drug delivery and radio-imaging applications. Nanomedicine Nanotechnology Biology and Medicine. 13(8):2495-2505. https://doi.org/10.1016/j.nano.2017.08.006 ; S ; 2495 ; 2505 ; 13 ; 8

2495 2505 13 8 ; S ; [EN] Mucin 1 (MUC1) is a cell surface protein overexpressed in breast cancer. Mesoporous silica nanoparticles (MSNs) loaded with safranin O, functionalized with aminopropyl groups and gated with the negatively charged MUC1 aptamer have been prepared (S1-apMUC1) for specific targeting and cargo release in tumoral versus non-tumoral cells. Confocal microscopy studies showed that the S1-apMUC1 nanoparticles were internalized in MDA-MB-231 breast cancer cells that overexpress MUC1 receptor with subsequent pore opening and cargo release. Interestingly, the MCF-10-A non-tumorigenic breast epithelial cell line that do not overexpress MUC1, showed reduced (S1-apMUC1) internalization. Negligible internalization was also found for S1-ap nanoparticles that contained a scrambled DNA sequence as gatekeeper. S2-apMUC1 nanoparticles (similar to S1-apMUC1 but loaded with doxorubicin) internalized in MDA-MB-231 cells and induced a remarkable reduction in cell viability. Moreover, S1-apMUC1 nanoparticles radio-labeled with Tc-99m (S1-apMUC1-Tc) showed a remarkable tumor targeting in in vivo studies with MDA-MB-231 tumor-bearing Balb/c mice. (C) 2017 Elsevier Inc. All rights reserved. Financial support from the Spanish Government and FEDER funds (Project MAT2015-64139-C4-1) and the Generalitat Valenciana (Project PROMETEOII/2014/047) is gratefully acknowledged. Pascual, L.; Cerqueira, C.; García-Fernández, A.; De Luis-Fernández, B.; Soares, E.; Souza, M.; Missailidis, S. (2017). MUC1 aptamer-capped mesoporous silica nanoparticles for controlled drug delivery and radio-imaging applications. Nanomedicine Nanotechnology Biology and Medicine. 13(8):2495-2505. https://doi.org/10.1016/j.nano.2017.08.006

[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 ...

[EN] The characteristics and electromechanical properties of conductive polymers together to their biocompatibility have boosted their application as a suitable tool in regenerative medicine and tissue engineering. However, conducting polymers as drug release materials are far from being ideal. A possibility to overcome this drawback is to combine conducting polymers with on-command delivery particles with inherent high-loading capacity. In this scenario, we report here the preparation of conduction polymers containing gated mesoporous silica nanoparticles (MSN) loaded with a cargo that is delivered on command by electro-chemical stimuli increasing the potential use of conducting polymers as controlled delivery systems. MSNs are loaded with Rhodamine B (Rh B), anchored to the conductive polymer poly(3,4-ethylenedioxythiophene) (PEDOT) doped with poly[(4-styrenesulfonic acid)-co-(maleic acid)], functionalized with a bipyridinium derivative and pores are capped with heparin (P3) by electrostatic interactions. P3 releases the entrapped cargo after the application of ¿640 mV voltage versus the saturated calomel electrode (SCE). Pore opening in the nanoparticles and dye delivery is ascribed to both (i) the reduction of the grafted bipyridinium derivative and (ii) the polarization of the conducting polymer electrode to negative potentials that induce detachment of positively charged heparin from the surface of the nanoparticles. Biocompatibility and cargo release studies were carried out in HeLa cells cultures. ; Alba Garcia-Fernandez, Beatriz Lozano-Torres contributed equally to this work. A. Garcia-Fernandez and B. Lozano-Torres are grateful to the "Ministerio de Economia y Competitividad" of the Spanish Government for her PhD fellowships. J. F. Blandez thanks the "Universitat Politecnica de Valencia" for his postdoctoral fellowship (PAID-10-17). The authors thank to the Spanish Government (Projects RTI2018-100910-B-C41 and RTI2018-101599-B-C22 (MCUI/AEI/FEDER, EU)) and the Generalitat Valencia (Project ...

[EN] Acute inflammation is a protective response of the body to harmful stimuli, such as pathogens or damaged cells. However, dysregulated inflammation can cause secondary damage and could thus contribute to the pathophysiology of many diseases. Inflammasomes, the macromolecular complexes responsible for caspase-1 activation, have emerged as key regulators of immune and inflammatory responses. Therefore, modulation of inflammasome activity has become an important therapeutic approach. Here we describe the design of a smart nanodevice that takes advantage of the passive targeting of nanoparticles to macrophages and enhances the therapeutic effect of caspase-1 inhibitor VX-765 in vivo. The functional hybrid systems consisted of MCM-41-based nanoparticles loaded with anti-inflammatory drug VX-765 (S2-P) and capped with poly-L-lysine, which acts as a molecular gate. S2-P activity has been evaluated in cellular and in vivo models of inflammation. The results indicated the potential advantage of using nanodevices to treat inflammatory diseases. (C) 2017 Elsevier B.V. All rights reserved. ; The authors wish to express their gratitude to the Spanish government (Projects MAT2015-64139-C4-1-R and SAF2014-52614-R (MINECO/FEDER)) and the Generalitat Valencia (Projects PROMETEOII/2014/061 and PROMETEOII/2014/047) for support. A.G-F. is grateful to the Spanish government for an FPU grant. ; García-Fernández, A.; García-Laínez, G.; Ferrandiz Manglano, ML.; Aznar, E.; Sancenón Galarza, F.; Alcaraz, MJ.; Murguía, JR. (2017). Targeting inflammasome by the inhibition of caspase-1 activity using capped mesoporous silica nanoparticles. Journal of Controlled Release. 248:60-70. https://doi.org/10.1016/j.jconrel.2017.01.002 ; S ; 60 ; 70 ; 248