Acetylcholinesterase-capped Mesoporous Silica Nanoparticles Controlled by the Presence of Inhibitors

[EN] Two different acetylcholinesterase (AChE)-capped mesoporous silica nanoparticles (MSNs), S1-AChE and S2-AChE, were prepared and characterized. MSNs were loaded with rhodamine B and the external surface was functionalized with either pyridostigmine derivative P1 (to yield solid S1) or neostigmine derivative P2 (to obtain S2). The final capped materials were obtained by coordinating grafted P1 or P2 with AChE ' s active sites (to give S1-AChE and S2-AChE, respectively). Both materials were able to release rho-damine B in the presence of diisopropylfluorophosphate (DFP) or neostigmine in a concentration-dependent manner via the competitive displacement of AChE through DFP and neostigmine coordination with the AChE ' s active sites. The responses of S1-AChE and S2-AChE were also tested with other enzyme inhibitors and substrates. These studies suggest that S1-AChE nanoparticles can be used for the selective detection of nerve agent simulant DFP and paraoxon.Financial support from the Spanish Government and FEDER funds (Project MAT2015‐64139‐C4‐1‐R, AGL2015‐70235‐C2‐2‐R) and the Generalitat Valencia (Project PROMETEOII/2014/047) is gratefully acknowledged. Ll. P. is grateful to the Universitat Politécnica de Valencia for his grant.Pascual, L.; El Sayed Shehata Nasr, S.; Marcos Martínez, MD.; Martínez-Máñez, R.; Sancenón Galarza, F. (2017). Acetylcholinesterase-capped Mesoporous Silica Nanoparticles Controlled by the Presence of Inhibitors. Chemistry - An Asian Journal. 12(7):775-784. https://doi.org/10.1002/asia.201700031S775784127Alberti, S., Soler-Illia, G. J. A. A., & Azzaroni, O. (2015). Gated supramolecular chemistry in hybrid mesoporous silica nanoarchitectures: controlled delivery and molecular transport in response to chemical, physical and biological stimuli. Chemical Communications, 51(28), 6050-6075. doi:10.1039/c4cc10414eAznar, E., Oroval, M., Pascual, L., Murguía, J. R., Martínez-Máñez, R., & Sancenón, F. (2016). Gated Materials for On-Command Release of Guest Molecules. Chemical Reviews, 116(2), 561-718. doi:10.1021/acs.chemrev.5b00456Coll, 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/ar3001469Slowing, I. I., Trewyn, B. G., Giri, S., & Lin, V. S.-Y. (2007). Mesoporous Silica Nanoparticles for Drug Delivery and Biosensing Applications. Advanced Functional Materials, 17(8), 1225-1236. doi:10.1002/adfm.200601191Yang, X., Liu, X., Liu, Z., Pu, F., Ren, J., & Qu, X. (2012). Near-Infrared Light-Triggered, Targeted Drug Delivery to Cancer Cells by Aptamer Gated Nanovehicles. Advanced Materials, 24(21), 2890-2895. doi:10.1002/adma.201104797Descalzo, A. B., Martínez-Máñez, R., Sancenón, F., Hoffmann, K., & Rurack, K. (2006). The Supramolecular Chemistry of Organic–Inorganic Hybrid Materials. Angewandte Chemie International Edition, 45(36), 5924-5948. doi:10.1002/anie.200600734Descalzo, A. B., Martínez-Máñez, R., Sancenón, F., Hoffmann, K., & Rurack, K. (2006). Die supramolekulare Chemie organisch-anorganischer Hybrid-Nanomaterialien. Angewandte Chemie, 118(36), 6068-6093. doi:10.1002/ange.200600734Beck, 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/ja00053a020Attard, G. S., Glyde, J. C., & Göltner, C. G. (1995). Liquid-crystalline phases as templates for the synthesis of mesoporous silica. Nature, 378(6555), 366-368. doi:10.1038/378366a0Kresge, 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:10.1038/359710a0Cai, Q., Luo, Z.-S., Pang, W.-Q., Fan, Y.-W., Chen, X.-H., & Cui, F.-Z. (2001). Dilute Solution Routes to Various Controllable Morphologies of MCM-41 Silica with a Basic Medium†. Chemistry of Materials, 13(2), 258-263. doi:10.1021/cm990661zChan, H. B. S., Budd, P. M., & Naylor, T. deV. (2001). Control of mesostructured silica particle morphology. Journal of Materials Chemistry, 11(3), 951-957. doi:10.1039/b005713oLi, Z., Barnes, J. C., Bosoy, A., Stoddart, J. F., & Zink, J. I. (2012). Mesoporous silica nanoparticles in biomedical applications. Chemical Society Reviews, 41(7), 2590. doi:10.1039/c1cs15246gAmbrogio, M. W., Thomas, C. R., Zhao, Y.-L., Zink, J. I., & Stoddart, J. F. (2011). Mechanized Silica Nanoparticles: A New Frontier in Theranostic Nanomedicine. Accounts of Chemical Research, 44(10), 903-913. doi:10.1021/ar200018xVallet-Regí, M., Balas, F., & Arcos, D. (2007). Mesoporous Materials for Drug Delivery. Angewandte Chemie International Edition, 46(40), 7548-7558. doi:10.1002/anie.200604488Vallet-Regí, M., Balas, F., & Arcos, D. (2007). Mesoporöse Materialien für den Wirkstofftransport. Angewandte Chemie, 119(40), 7692-7703. doi:10.1002/ange.200604488Sancenón, F., Pascual, L., Oroval, M., Aznar, E., & Martínez-Máñez, R. (2015). Gated Silica Mesoporous Materials in Sensing Applications. ChemistryOpen, 4(4), 418-437. doi:10.1002/open.201500053Radhakrishnan, K., Tripathy, J., Gnanadhas, D. P., Chakravortty, D., & Raichur, A. M. (2014). Dual enzyme responsive and targeted nanocapsules for intracellular delivery of anticancer agents. RSC Adv., 4(86), 45961-45968. doi:10.1039/c4ra07815bPatel, 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/ja0772086De la Torre, C., Mondragón, L., Coll, C., Sancenón, F., Marcos, M. D., Martínez-Máñez, R., … Orzáez, M. (2014). Cathepsin-B Induced Controlled Release from Peptide-Capped Mesoporous Silica Nanoparticles. Chemistry - A European Journal, 20(47), 15309-15314. doi:10.1002/chem.201404382Agostini, 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/la303161eCandel, 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/c2nr32062bMas, N., Agostini, A., Mondragón, L., Bernardos, A., Sancenón, F., Marcos, M. D., … Pérez-Payá, E. (2012). Enzyme-Responsive Silica Mesoporous Supports Capped with Azopyridinium Salts for Controlled Delivery Applications. Chemistry - A European Journal, 19(4), 1346-1356. doi:10.1002/chem.201202740Bernardos, A., Aznar, E., Marcos, M. D., Martínez-Máñez, R., Sancenón, F., Soto, J., … Amorós, P. (2009). Enzyme-Responsive Controlled Release Using Mesoporous Silica Supports Capped with Lactose. Angewandte Chemie International Edition, 48(32), 5884-5887. doi:10.1002/anie.200900880Bernardos, A., Aznar, E., Marcos, M. D., Martínez-Máñez, R., Sancenón, F., Soto, J., … Amorós, P. (2009). Enzyme-Responsive Controlled Release Using Mesoporous Silica Supports Capped with Lactose. Angewandte Chemie, 121(32), 5998-6001. doi:10.1002/ange.200900880Zhu, Y., Meng, W., & Hanagata, N. (2011). Cytosine-phosphodiester-guanine oligodeoxynucleotide (CpG ODN)-capped hollow mesoporous silica particles for enzyme-triggered drug delivery. Dalton Transactions, 40(39), 10203. doi:10.1039/c1dt11114kAgostini, 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.201204663Aznar, E., Villalonga, R., Giménez, C., Sancenón, F., Marcos, M. D., Martínez-Máñez, R., … Amorós, P. (2013). Glucose-triggered release using enzyme-gated mesoporous silica nanoparticles. Chemical Communications, 49(57), 6391. doi:10.1039/c3cc42210kChen, 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/c2cc34290aDíez, P., Sánchez, A., Gamella, M., Martínez-Ruíz, P., Aznar, E., de la Torre, C., … Pingarrón, J. M. (2014). Toward the Design of Smart Delivery Systems Controlled by Integrated Enzyme-Based Biocomputing Ensembles. Journal of the American Chemical Society, 136(25), 9116-9123. doi:10.1021/ja503578bDíez, P., Sánchez, A., Torre, C. de la, Gamella, M., Martínez-Ruíz, P., Aznar, E., … Villalonga, R. (2016). Neoglycoenzyme-Gated Mesoporous Silica Nanoparticles: Toward the Design of Nanodevices for Pulsatile Programmed Sequential Delivery. ACS Applied Materials & Interfaces, 8(12), 7657-7665. doi:10.1021/acsami.5b12645Yang, X., Pu, F., Chen, C., Ren, J., & Qu, X. (2012). An enzyme-responsive nanocontainer as an intelligent signal-amplification platform for a multiple proteases assay. Chemical Communications, 48(90), 11133. doi:10.1039/c2cc36340bDatz, S., Argyo, C., Gattner, M., Weiss, V., Brunner, K., Bretzler, J., … Bein, T. (2016). Genetically designed biomolecular capping system for mesoporous silica nanoparticles enables receptor-mediated cell uptake and controlled drug release. Nanoscale, 8(15), 8101-8110. doi:10.1039/c5nr08163gSun, X., Zhao, Y., Lin, V. S.-Y., Slowing, I. I., & Trewyn, B. G. (2011). Luciferase and Luciferin Co-immobilized Mesoporous Silica Nanoparticle Materials for Intracellular Biocatalysis. Journal of the American Chemical Society, 133(46), 18554-18557. doi:10.1021/ja2080168Liu, P., Wang, X., Hiltunen, K., & Chen, Z. (2015). Controllable Drug Release System in Living Cells Triggered by Enzyme–Substrate Recognition. ACS Applied Materials & Interfaces, 7(48), 26811-26818. doi:10.1021/acsami.5b08914Wang, X., Liu, P., Chen, Z., & Shen, J. (2016). A drug release switch based on protein-inhibitor supramolecular interaction. RSC Advances, 6(30), 25480-25484. doi:10.1039/c6ra03543dRim, H. P., Min, K. H., Lee, H. J., Jeong, S. Y., & Lee, S. C. (2011). pH-Tunable Calcium Phosphate Covered Mesoporous Silica Nanocontainers for Intracellular Controlled Release of Guest Drugs. Angewandte Chemie International Edition, 50(38), 8853-8857. doi:10.1002/anie.201101536Rim, H. P., Min, K. H., Lee, H. J., Jeong, S. Y., & Lee, S. C. (2011). pH-Tunable Calcium Phosphate Covered Mesoporous Silica Nanocontainers for Intracellular Controlled Release of Guest Drugs. Angewandte Chemie, 123(38), 9015-9019. doi:10.1002/ange.201101536Zhao, W., Zhang, H., He, Q., Li, Y., Gu, J., Li, L., … Shi, J. (2011). A glucose-responsive controlled release of insulin system based on enzyme multilayers-coated mesoporous silica particles. Chemical Communications, 47(33), 9459. doi:10.1039/c1cc12740cEl Sayed, S., Milani, M., Milanese, C., Licchelli, M., Martínez-Máñez, R., & Sancenón, F. (2016). Anions as Triggers in Controlled Release Protocols from Mesoporous Silica Nanoparticles Functionalized with Macrocyclic Copper(II) Complexes. Chemistry - A European Journal, 22(39), 13935-13945. doi:10.1002/chem.201601024Tukappa, A., Ultimo, A., de la Torre, C., Pardo, T., Sancenón, F., & Martínez-Máñez, R. (2016). Polyglutamic Acid-Gated Mesoporous Silica Nanoparticles for Enzyme-Controlled Drug Delivery. Langmuir, 32(33), 8507-8515. doi:10.1021/acs.langmuir.6b01715Giménez, C., Climent, E., Aznar, E., Martínez-Máñez, R., Sancenón, F., Marcos, M. D., … Rurack, K. (2014). Über den chemischen Informationsaustausch zwischen gesteuerten Nanopartikeln. Angewandte Chemie, 126(46), 12838-12843. doi:10.1002/ange.201405580De la Torre, C., Agostini, A., Mondragón, L., Orzáez, M., Sancenón, F., Martínez-Máñez, R., … Pérez-Payá, E. (2014). Temperature-controlled release by changes in the secondary structure of peptides anchored onto mesoporous silica supports. Chem. Commun., 50(24), 3184-3186. doi:10.1039/c3cc49421gOroval, 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/c3cc42157kPascual, L., Sayed, S. E., Martínez-Máñez, R., Costero, A. M., Gil, S., Gaviña, P., & Sancenón, F. (2016). Acetylcholinesterase-Capped Mesoporous Silica Nanoparticles That Open in the Presence of Diisopropylfluorophosphate (a Sarin or Soman Simulant). Organic Letters, 18(21), 5548-5551. doi:10.1021/acs.orglett.6b02793Comes, M., Rodríguez-López, G., Marcos, M. D., Martínez-Máñez, R., Sancenón, F., Soto, J., … Beltrán, D. (2005). Host Solids Containing Nanoscale Anion-Binding Pockets and Their Use in Selective Sensing Displacement Assays. Angewandte Chemie International Edition, 44(19), 2918-2922. doi:10.1002/anie.200461511Comes, M., Rodríguez-López, G., Marcos, M. D., Martínez-Máñez, R., Sancenón, F., Soto, J., … Beltrán, D. (2005). Host Solids Containing Nanoscale Anion-Binding Pockets and Their Use in Selective Sensing Displacement Assays. Angewandte Chemie, 117(19), 2978-2982. doi:10.1002/ange.200461511Lorke, D. E., Hasan, M. Y., Arafat, K., Kuča, K., Musilek, K., Schmitt, A., & Petroianu, G. A. (2008). In vitro oxime protection of human red blood cell acetylcholinesterase inhibited by diisopropyl-fluorophosphate. Journal of Applied Toxicology, 28(4), 422-429. doi:10.1002/jat.1344Petroianu, G., Kühn, F., Thyes, C., Ewald, V., & Missler, A. (2003). In vitroprotection of plasma cholinesterases by metoclopramide from inhibition by paraoxon. Journal of Applied Toxicology, 23(1), 75-79. doi:10.1002/jat.891Grove, S. J. A., Kaur, J., Muir, A. W., Pow, E., Tarver, G. J., & Zhang, M.-Q. (2002). Oxyaniliniums as acetylcholinesterase inhibitors for the reversal of neuromuscular block. Bioorganic & Medicinal Chemistry Letters, 12(2), 193-196. doi:10.1016/s0960-894x(01)00703-xRoyo, S., Martínez-Máñez, R., Sancenón, F., Costero, A. M., Parra, M., & Gil, S. (2007). Chromogenic and fluorogenic reagents for chemical warfare nerve agents’ detection. Chemical Communications, (46), 4839. doi:10.1039/b707063bFan, C., Tsui, L., & Liao, M.-C. (2011). Parathion degradation and its intermediate formation by Fenton process in neutral environment. Chemosphere, 82(2), 229-236. doi:10.1016/j.chemosphere.2010.10.016Fomsgaard, I. S. (1995). Degradation of Pesticides in Subsurface Soils, Unsaturated Zone—a Review Of Methods and Results. International Journal of Environmental Analytical Chemistry, 58(1-4), 231-245. doi:10.1080/03067319508033127Turan, J., Kesik, M., Soylemez, S., Goker, S., Coskun, S., Unalan, H. E., & Toppare, L. (2016). An effective surface design based on a conjugated polymer and silver nanowires for the detection of paraoxon in tap water and milk. Sensors and Actuators B: Chemical, 228, 278-286. doi:10.1016/j.snb.2016.01.034Funari, R., Della Ventura, B., Carrieri, R., Morra, L., Lahoz, E., Gesuele, F., … Velotta, R. (2015). Detection of parathion and patulin by quartz-crystal microbalance functionalized by the photonics immobilization technique. Biosensors and Bioelectronics, 67, 224-229. doi:10.1016/j.bios.2014.08.020Fu, G., Chen, W., Yue, X., & Jiang, X. (2013). Highly sensitive colorimetric detection of organophosphate pesticides using copper catalyzed click chemistry. Talanta, 103, 110-115. doi:10.1016/j.talanta.2012.10.016Wang, K., Wang, L., Jiang, W., & Hu, J. (2011). A sensitive enzymatic method for paraoxon detection based on enzyme inhibition and fluorescence quenching. Talanta, 84(2), 400-405. doi:10.1016/j.talanta.2011.01.05

Chloride channels and anion fluxes in a human colonic epithelium (HCA-7).

1. Colonic epithelial cells, derived from a human adenocarcinoma (HCA-7), were examined by the patch clamp technique. 2. Outwardly rectifying anion (Cl-) channels were identified in the apical membrane. The conductance was g(in) approximately 26 pS, g(out) approximately 40 pS. The open state probability of the channels increased with depolarization and the selectivity for Cl- over K+ (PCl/PK) was approximately 7.5. 3. The channels were sensitive to intracellular adenosine 3':5'-cyclic monophosphate (cyclic AMP, 0.1 mM), but not to Ca2+ (at concentrations up to 1 mM). At depolarized potentials the channels were blocked by pirentanide (1-5 microM) applied intracellularly. 4. HCA-7 monolayers loaded with 125I- (as a marker for Cl-) were used to measure I- efflux and converted to instantaneous rate constants. 5. The rate constant for I- efflux was increased by forskolin and lysylbradykinin (LBK). The effects of forskolin were not effected by BAPTA (an intracellular calcium chelator). The effects of LBK were inhibited by BAPTA and by Ba2+, indicating that LBK raised intracellular Ca2+ (Cai) which activates Ca(2+)-sensitive K-channels, the latter being blocked by Ba2+. 6. Although it cannot be conclusively proved that the outwardly rectifying chloride channels described here are solely or partially responsible for the increased anion efflux or transepithelial chloride secretion, the channels are likely to be more relevant for cyclic AMP-requiring rather than Ca(2+)-requiring secretagogues

High-efficiency indium gallium nitride/Si tandem photovoltaic solar cells modeling using indium gallium nitride semibulk material: monolithic integration versus 4-terminal tandem cells

International audienc