Toxicological Profiling and Long-Term Effects of Bare, PEGylated- and Galacto-Oligosaccharide-Functionalized Mesoporous Silica Nanoparticles

[EN] Mesoporous silica nanoparticles (MSNs) are amongst the most used nanoparticles in biomedicine. However, the potentially toxic effects of MSNs have not yet been fully evaluated, being a controversial matter in research. In this study, bare MSNs, PEGylated MSNs (MSNs-PEG), and galacto-oligosaccharide-functionalized MSNs (MSNs-GAL) are synthesized and characterized to assess their genotoxicity and transforming ability on human lung epithelial BEAS-2B cells in short- (48 h) and long-term (8 weeks) exposure scenarios. Initial short-term treatments show a dose-dependent increase in genotoxicity for MSNs-PEG-treated cells but not oxidative DNA damage for MSNs, MSNs-PEG, or for MSNs-GAL. In addition, after 8 weeks of continuous exposure, neither induced genotoxic nor oxidative DNA is observed. Nevertheless, long-term treatment with MSNsPEG and MSNs-GAL, but not bare MSNs, induces cell transformation features, as evidenced by the cell¿s enhanced ability to grow independently of anchorage, to migrate, and to invade. Further, the secretome from cells treated with MSNs and MSNs-GAL, but not MSNs-PEG, shows certain tumor-promoting abilities, increasing the number and size of HeLa cell colonies formed in the indirect soft-agar assay. These results show that MSNs, specifically the functionalized ones, provoke some measurable adverse effects linked to tumorigenesis. These effects are in the order of other nanomaterials, such as carbon nanotubes or cerium dioxide nanoparticles, but they are lower than those provoked by some approved drugs, such as doxorubicin or dexamethasone.This work was supported by PID2021-126304OB-C41, PID2021-128141OB-C22, and PID2020-116789RB-C43 funded by MCIN/AEI/10.13039/501100011033/, by the European Regional Development Fund `A way of doing Europe¿, by Generalitat Valenciana (CIPROM/2021/007), and by the Generalitat de Catalunya (2021-SGR-00731). The work was also supported by CIBER `Consorcio Centro de Investigación Biomédica en Red¿ (CB06/01/2012), Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación. This study forms part of the Advanced Materials programme (MFA/2022/049) and was supported by MCIN with funding from European Union NextGenerationEU (PRTR-C17.I1) and from Generalitat Valenciana. This project has also received funding from the European Union¿s Horizon 2020 Research and Innovation Programme under Grant Agreement No. 965196. Alba Hernández was granted an ICREA ACADEMIA award. Vicente Candela-Noguera thanks the Spanish Government for his fellowship (FPU15/02753). Paula Díez thanks the Generalitat Valenciana for her contract APOSTD/2020/153 and thanks the Instituto de Salud Carlos III and the European Social Fund for the financial support `Sara Borrell¿, CD20/00120. The authors thank the Electron Microscopy Service at UPV for support.Barguilla, I.; Candela-Noguera, V.; Oliver, P.; Annangi, B.; Diez-Sánchez, P.; Aznar, E.; Martínez-Máñez, R.... (2023). Toxicological Profiling and Long-Term Effects of Bare, PEGylated- and Galacto-Oligosaccharide-Functionalized Mesoporous Silica Nanoparticles. International Journal of Molecular Sciences. 24(22):1-14. https://doi.org/10.3390/ijms242216158114242

Nanoprogrammed Cross-Kingdom Communication Between Living Microorganisms

[EN] The engineering of chemical communication at the micro/nanoscale is a key emergent topic in micro/nanotechnology, synthetic biology, and related areas. However, the field is still in its infancy; previous advances, although scarce, have mainly focused on communication between abiotic micro/nanosystems or between microvesicles and living cells. Here, we have implemented a nanoprogrammed cross-kingdom communication involving two different microorganisms and tailor-made nanodevices acting as "nanotranslators". Information flows from the sender cells (bacteria) to the nanodevice and from the nanodevice to receiver cells (yeasts) in a hierarchical way, allowing communication between two microorganisms that otherwise would not interact.B.d.L. is grateful to the Spanish Government for her FPU Ph.D. fellowship. The authors wish to thank the Spanish Government (projects RTI2018-100910-B-C41 and RTI2018101599-B-C22 (MCUI/FEDER, EU)) and the Generalitat Valenciana (project PROMETEO 2018/024) for support. Part of this work was included in the Ph.D. thesis of B.d.L.De Luis-Fernández, B.; Morella-Aucejo, Á.; Llopis-Lorente, A.; Martínez-Latorre, J.; Sancenón Galarza, F.; López Del Rincón, C.; Murguía, JR.... (2022). Nanoprogrammed Cross-Kingdom Communication Between Living Microorganisms. Nano Letters. 22(5):1836-1844. https://doi.org/10.1021/acs.nanolett.1c024351836184422

4-(4,5-Diphenyl-1H-imidazole-2-yl)-N,N-dimethylaniline-Cu(II) complex, a highly selective probe for glutathione sensing in water-acetonitrile mixtures

The imidazole derivative 4-(4,5-diphenyl-1H-imidazol-2-yl)-N,N-dimethylaniline (probe 1) formed a highly coloured and non-emissive 1:1 stoichiometry complex with Cu(II) in water-acetonitrile 1:1 (v/v) solutions. Among all the amino acids (Lys, Val, Gln, Leu, His, Thr, Trp, Gly, Phe, Arg, Ile, Met, Ser, Ala, Pro, Tyr, Gly, Asn, Asp, Glu, Cys and Hcy) and tripeptides (GSH) tested, only GSH induced the bleaching of the 1·Cu(II) solution together with a marked emission enhancement at 411 nm (excitation at 320 nm). These chromo-fluorogenic changes were ascribed to a selective GSH-induced demetallation of the 1·Cu(II) complex that resulted in a recovery of the spectroscopic features of probe 1. In addition to the remarkable selectivity of 1·Cu(II) complex toward GSH a competitive limit of detection as low as 2 μM was determined using fluorescence measurements.We thank the Spanish Government (MAT2015-64139-C4-1-R) and Generalitat Valenciana (PROMETEOII/2014/047). H. E. O. thanks Generalitat Valenciana for his Grisolia fellowship. Thanks are also due to Fundação para a Ciência e Tecnologia (Portugal) for financial support to the Portuguese NMR network (PTNMR, Bruker Avance III 400-Univ. Minho), FCT and FEDEReCOMPETEQREN-EU for financial support to the research centre CQUM (UID/QUI/0686/2016) and a doctoral grant to R.C.M. Ferreira (SFRH/BD/86408/2012). The NMR spectrometers are part of the National NMR Network (PTNMR) and are partially supported by Infrastructure Project No 022161 (co-financed by FEDER through COMPETE 2020, POCI and PORL and FCT through PIDDAC).info:eu-repo/semantics/publishedVersio

Nanoparticle-cell-nanoparticle communication by stigmergy to enhance poly(I:C) induced apoptosis in cancer cells

[EN] Nanoparticle-cell-nanoparticle communication by stigmergy was demonstrated using two capped nanodevices. The first community of nanoparticles (i.e.S(RA)(IFN)) is loaded with 9-cis-retinoic acid and capped with interferon-gamma, whereas the second community of nanoparticles (i.e.S(sulf)(PIC)) is loaded with sulforhodamine B and capped with poly(I:C). The uptake ofS(RA)(IFN)by SK-BR-3 breast cancer cells enhanced the expression of TLR3 receptor facilitating the subsequent uptake ofS(sulf)(PIC)and cell killing.We thank the Spanish Government (projects RTI2018-100910-B-C41 and RTI2018-101599-B-C22 (MCUI/FEDER, EU)), Generalitat Valenciana (project PROMETEO2018/024) and CIBER-BBN (project NANOCOMMUNITY) for support. A. U. and C. G are grateful to the Ministry of Education, Culture and Sport for her doctoral FPU grant.Ultimo, A.; De La Torre-Paredes, C.; Giménez, C.; Aznar, E.; Coll, C.; Marcos Martínez, MD.; Murguía, JR.... (2020). Nanoparticle-cell-nanoparticle communication by stigmergy to enhance poly(I:C) induced apoptosis in cancer cells. Chemical Communications. 56(53):7273-7276. https://doi.org/10.1039/d0cc02795bS727372765653Schaming, D., & Remita, H. (2015). Nanotechnology: from the ancient time to nowadays. Foundations of Chemistry, 17(3), 187-205. doi:10.1007/s10698-015-9235-yHauert, S., & Bhatia, S. N. (2014). Mechanisms of cooperation in cancer nanomedicine: towards systems nanotechnology. Trends in Biotechnology, 32(9), 448-455. doi:10.1016/j.tibtech.2014.06.010Theraulaz, G., & Bonabeau, E. (1999). A Brief History of Stigmergy. Artificial Life, 5(2), 97-116. doi:10.1162/106454699568700Llopis-Lorente, A., Díez, P., Sánchez, A., Marcos, M. D., Sancenón, F., Martínez-Ruiz, P., … Martínez-Máñez, R. (2017). Interactive models of communication at the nanoscale using nanoparticles that talk to one another. Nature Communications, 8(1). doi:10.1038/ncomms15511Luis, B., Llopis‐Lorente, A., Rincón, P., Gadea, J., Sancenón, F., Aznar, E., … Martínez‐Máñez, R. (2019). An Interactive Model of Communication between Abiotic Nanodevices and Microorganisms. Angewandte Chemie International Edition, 58(42), 14986-14990. doi:10.1002/anie.201908867De la Torre, C., Domínguez-Berrocal, L., Murguía, J. R., Marcos, M. D., Martínez-Máñez, R., Bravo, J., & Sancenón, F. (2018). ϵ -Polylysine-Capped Mesoporous Silica Nanoparticles as Carrier of the C 9h Peptide to Induce Apoptosis in Cancer Cells. Chemistry - A European Journal, 24(8), 1890-1897. doi:10.1002/chem.201704161García-Fernández, A., García-Laínez, G., Ferrándiz, M. L., Aznar, E., Sancenón, F., Alcaraz, M. J., … Orzáez, M. (2017). Targeting inflammasome by the inhibition of caspase-1 activity using capped mesoporous silica nanoparticles. Journal of Controlled Release, 248, 60-70. doi:10.1016/j.jconrel.2017.01.002Murugan, C., Rayappan, K., Thangam, R., Bhanumathi, R., Shanthi, K., Vivek, R., … Kannan, S. (2016). Combinatorial nanocarrier based drug delivery approach for amalgamation of anti-tumor agents in breast cancer cells: an improved nanomedicine strategy. Scientific Reports, 6(1). doi:10.1038/srep34053Van Rijt, S. H., Bölükbas, D. A., Argyo, C., Datz, S., Lindner, M., Eickelberg, O., … Meiners, S. (2015). Protease-Mediated Release of Chemotherapeutics from Mesoporous Silica Nanoparticles to ex Vivo Human and Mouse Lung Tumors. ACS Nano, 9(3), 2377-2389. doi:10.1021/nn5070343Llopis-Lorente, A., Lozano-Torres, B., Bernardos, A., Martínez-Máñez, R., & Sancenón, F. (2017). Mesoporous silica materials for controlled delivery based on enzymes. Journal of Materials Chemistry B, 5(17), 3069-3083. doi:10.1039/c7tb00348jBianchi, F., Pretto, S., Tagliabue, E., Balsari, A., & Sfondrini, L. (2017). Exploiting poly(I:C) to induce cancer cell apoptosis. Cancer Biology & Therapy, 18(10), 747-756. doi:10.1080/15384047.2017.1373220Ultimo, A., Giménez, C., Bartovsky, P., Aznar, E., Sancenón, F., Marcos, M. D., … Murguía, J. R. (2016). Targeting Innate Immunity with dsRNA-Conjugated Mesoporous Silica Nanoparticles Promotes Antitumor Effects on Breast Cancer Cells. Chemistry - A European Journal, 22(5), 1582-1586. doi:10.1002/chem.201504629Bernardo, A. R., Cosgaya, J. M., Aranda, A., & Jiménez-Lara, A. M. (2013). Synergy between RA and TLR3 promotes type I IFN-dependent apoptosis through upregulation of TRAIL pathway in breast cancer cells. Cell Death & Disease, 4(1), e479-e479. doi:10.1038/cddis.2013.5Clarke, N., Jimenez-Lara, A. M., Voltz, E., & Gronemeyer, H. (2004). Tumor suppressor IRF-1 mediates retinoid and interferon anticancer signaling to death ligand TRAIL. The EMBO Journal, 23(15), 3051-3060. doi:10.1038/sj.emboj.7600302Kajita, A. i., Morizane, S., Takiguchi, T., Yamamoto, T., Yamada, M., & Iwatsuki, K. (2015). Interferon-Gamma Enhances TLR3 Expression and Anti-Viral Activity in Keratinocytes. Journal of Investigative Dermatology, 135(8), 2005-2011. doi:10.1038/jid.2015.125Weihua, X., Kolla, V., & Kalvakolanu, D. V. (1997). Modulation of Interferon Action by Retinoids. Journal of Biological Chemistry, 272(15), 9742-9748. doi:10.1074/jbc.272.15.974

Synthesis and evaluation of fluorimetric and colorimetric chemosensors for anions based on (oligo)thienyl-thiosemicarbazones

A family of heterocyclic thiosemicarbazone dyes (3a-d) containing thienyl groups has been synthesized, characterized and their chromo-fluorogenic response in acetonitrile in the presence of selected anions studied. Acetonitrile solutions of 3a-d show absorption bands in the 338-425 nm range which are modulated by the groups attached to the thiosemicarbazone moiety. The fluoride, chloride, bromide, iodide, dihydrogen phosphate, hydrogen sulfate, nitrate, acetate and anions were used in the recognition studies. Only sensing features were observed for fluoride, cyanide, acetate and dihydrogen phosphate anions. Two different chromogenic responses were found, (i) a small shift of the absorption band due to coordination of the anions with the thiourea protons and (ii) the appearance of a new red shifted band due to deprotonation of the receptor. For the latter process changes in the color solutions from pale-yellow to orange-red were observed. Fluorescence studies showed a different emission behavior according to the number of thienyl rings in the π-conjugated bridges. Stability constants for the two processes (complex formation + deprotonation) for receptors 3a-d in the presence of fluoride and acetate anions were determined from spectrophotometric titrations using the HypSpec program. The interaction of 3d with fluoride was also studied through 1H NMR titrations. Semiempirical calculations to evaluate the hydrogen-donating ability of the receptors were also performed.Fundação para a Ciência e a Tecnologia (FCT) , Acções Integradas Luso-Espanholas/CRUP, Generalitat Valenci

Enzyme-Powered Gated Mesoporous Silica Nanomotors for On-Command Intracellular Payload Delivery

[EN] The introduction of stimuli-responsive cargo release capabilities on self-propelled micro- and nano- motors holds enormous potential in a number of applications in the biomedical field. Herein, we report the preparation of mesoporous silica nano-particles gated with pH-responsive supramolecular nanovalves and equipped with urease enzymes which act as chemical engines to power the nanomotors. The nanoparticles are loaded with different cargo molecules ([Ru(bpy)(3)]Cl-2 (bpy = 2,2'-bipyridine) or doxorubicin), grafted with benzimidazole groups on the outer surface, and capped by the formation of inclusion complexes between benzimidazole and cyclodextrin-modified urease. The nanomotor exhibits enhanced Brownian motion in the presence of urea. Moreover, no cargo is released at neutral pH, even in the presence of the biofuel urea, due to the blockage of the pores by the bulky benzimidazole:cyclodextrin-urease caps. Cargo delivery is only triggered on-command at acidic pH due to the protonation of benzimidazole groups, the dethreading of the supramolecular nanovalves, and the subsequent uncapping of the nanoparticles. Studies with HeLa cells indicate that the presence of biofuel urea enhances nanoparticle internalization and both [Ru(bpy)(3)]Cl-2 or doxorubicin intracellular release due to the acidity of lysosomal compartments. Gated enzyme-powered nanomotors shown here display some of the requirements for ideal drug delivery carriers such as the capacity to self-propel and the ability to "sense" the environment and deliver the payload on demand in response to predefined stimuli.A.L.-L. is grateful to La Caixa Banking Foundation for his Ph.D. grant. A.G.-F. thanks the Spanish government for her FPU fellowship. The authors are grateful to the Spanish Government (MINECO Projects MAT2015-64139-C4-1, CTQ2014-58989- PCTQ2015-71936-REDT, CTQ2015-68879-R (MICRODIA) and CTQ2015-72471-EXP (Enzwim)), the BBVA foundation (MEDIROBOTS), the CERCA Programme by the Generalitat de Catalunya, and the Generalitat Valenciana (Project PROMETEO/2018/024 and PROMETEOII/2014/061) for support. T.P. thanks MINECO for the Juan de la Cierva postdoctoral fellowship and the European Union's Horizon 2020 research and innovation program, under the Marie Sk¿odowska-Curie Individual Fellowship (H2020-MSCA-IF2018, DNA-bots). A.C.H. thanks MINECO for the Severo Ochoa fellowship. The authors would like to thank A. Miguel Lopez for the development of the python code for motion analysis.Llopis-Lorente, A.; García-Fernández, A.; Murillo-Cremaes, N.; Hortelao, A.; Patiño, T.; Villalonga, R.; Sancenón Galarza, F.... (2019). Enzyme-Powered Gated Mesoporous Silica Nanomotors for On-Command Intracellular Payload Delivery. ACS Nano. 13(10):12171-12183. https://doi.org/10.1021/acsnano.9b067061217112183131

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

Targeting inflammasome by the inhibition of caspase-1 activity using capped mesoporous silica nanoparticles

[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.2017.01.002S607024

Nonordered dendritic mesoporous silica nanoparticles as promising platforms for advanced methods of diagnosis and therapies

Dendritic mesoporous silica nanoparticles (DMSNs) are a new generation of porous materials that have gained great attention compared to other mesoporous silicas due to attractive properties, including straightforward synthesis methods, modular surface chemistry, high surface area, tunable pore size, chemical inertness, particle size distribution, excellent biocompatibility, biodegradability, and high pore volume compared with conventional mesoporous materials. The last years have witnessed a blooming growth of the extensive utilization of DMSNs as an efficient platform in a broad spectrum of biomedical and industrial applications, such as catalysis, energy harvesting, biosensing, drug/gene delivery, imaging, theranostics, and tissue engineering. DMSNs are considered great candidates for nanomedicine applications due to their ease of surface functionalization for targeted and controlled therapeutic delivery, high therapeutic loading capacity, minimizing adverse effects, and enhancing biocompatibility. In this review, we will extensively detail state-of-the-art studies on recent advances in synthesis methods, structure, properties, and applications of DMSNs in the biomedical field with an emphasis on the different delivery routes, cargos, and targeting approaches and a wide range of therapeutic, diagnostic, tissue engineering, vaccination applications and challenges and future implications of DMSNs as cuttingedge technology in medicine

Janus Gold Nanostars-Mesoporous Silica Nanoparticles for NIR-Light-Triggered Drug Delivery

"This is the peer reviewed version of the following article: Hernández Montoto, Andy, Antoni Llopis-Lorente, Mónica Gorbe, José M. Terrés, Roberto Cao Milán, Borja Díaz de Greñu, María Alfonso, et al. 2019. Janus Gold Nanostars Mesoporous Silica Nanoparticles for NIR-Light-Triggered Drug Delivery. Chemistry A European Journal 25 (36). Wiley: 8471 78. doi:10.1002/chem.201900750, which has been published in final form at https://doi.org/10.1002/chem.201900750. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving."[EN] Janus gold nanostar-mesoporous silica nanoparticle (AuNSt-MSNP) nanodevices able to release an entrapped payload upon irradiation with near infrared (NIR) light were prepared and characterized. The AuNSt surface was functionalized with a thiolated photolabile molecule (5), whereas the mesoporous silica face was loaded with a model drug (doxorubicin) and capped with proton-responsive benzimidazole-beta-cyclodextrin supramolecular gatekeepers (N 1). Upon irradiation with NIR-light, the photolabile compound 5 photodissociated, resulting in the formation of succinic acid, which induced the opening of the gatekeeper and cargo delivery. In the overall mechanism, the gold surface acts as a photochemical transducer capable of transforming the NIR-light input into a chemical messenger (succinic acid) that opens the supramolecular nanovalve. The prepared hybrid nanoparticles were non-cytotoxic to HeLa cells, until they were irradiated with a NIR laser, which led to intracellular doxorubicin release and hyperthermia. This induced a remarkable reduction in HeLa cells viability.The authors gratefully acknowledge financial support from the Spanish Government [Projects MAT2015-64139-C4-1-R, AGL2015-70235-C2-2-R and SAF2017-84689-R (MINECO/AEI/FEDER, UE)], the Generalitat Valenciana (Project PROMETEO2018/024) and European Union (Erasmus Mundus Programme, Action 2, grant agreement number 2014-0870/001001). A.H. thanks the Erasmus Mundus Programme for his PhD scholarship through the EuroInkaNet project. A.L.-L. thanks "La Caixa" Banking Foundation for his PhD scholarship.Hernández-Montoto, A.; Llopis-Lorente, A.; Gorbe, M.; Terrés-Haro, JM.; Cao Milán, R.; Díaz De Greñu-Puertas, B.; Alfonso-Navarro, M.... (2019). Janus Gold Nanostars-Mesoporous Silica Nanoparticles for NIR-Light-Triggered Drug Delivery. Chemistry - A European Journal. 25(36):8471-8478. https://doi.org/10.1002/chem.201900750S847184782536Yang, P., Gai, S., & Lin, J. (2012). Functionalized mesoporous silica materials for controlled drug delivery. Chemical Society Reviews, 41(9), 3679. doi:10.1039/c2cs15308dSancenón, 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.201500053Giménez, C., Climent, E., Aznar, E., Martínez-Máñez, R., Sancenón, F., Marcos, M. D., … Rurack, K. (2014). Towards Chemical Communication between Gated Nanoparticles. Angewandte Chemie International Edition, n/a-n/a. doi:10.1002/anie.201405580Giménez, 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.201405580Llopis-Lorente, A., Díez, P., Sánchez, A., Marcos, M. D., Sancenón, F., Martínez-Ruiz, P., … Martínez-Máñez, R. (2017). Interactive models of communication at the nanoscale using nanoparticles that talk to one another. Nature Communications, 8(1). doi:10.1038/ncomms15511Song, N., & Yang, Y.-W. (2015). Molecular and supramolecular switches on mesoporous silica nanoparticles. Chemical Society Reviews, 44(11), 3474-3504. doi:10.1039/c5cs00243eAznar, 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.5b00456Koutsopoulos, S. (2012). Molecular fabrications of smart nanobiomaterials and applications in personalized medicine. Advanced Drug Delivery Reviews, 64(13), 1459-1476. doi:10.1016/j.addr.2012.08.002Bao, G., Mitragotri, S., & Tong, S. (2013). Multifunctional Nanoparticles for Drug Delivery and Molecular Imaging. Annual Review of Biomedical Engineering, 15(1), 253-282. doi:10.1146/annurev-bioeng-071812-152409Hernández Montoto, A., Montes, R., Samadi, A., Gorbe, M., Terrés, J. M., Cao-Milán, R., … Martínez-Máñez, R. (2018). Gold Nanostars Coated with Mesoporous Silica Are Effective and Nontoxic Photothermal Agents Capable of Gate Keeping and Laser-Induced Drug Release. ACS Applied Materials & Interfaces, 10(33), 27644-27656. doi:10.1021/acsami.8b08395De la Torre, C., Domínguez-Berrocal, L., Murguía, J. R., Marcos, M. D., Martínez-Máñez, R., Bravo, J., & Sancenón, F. (2018). ϵ -Polylysine-Capped Mesoporous Silica Nanoparticles as Carrier of the C 9h Peptide to Induce Apoptosis in Cancer Cells. Chemistry - A European Journal, 24(8), 1890-1897. doi:10.1002/chem.201704161Teruel, A. H., Pérez-Esteve, É., González-Álvarez, I., González-Álvarez, M., Costero, A. M., Ferri, D., … Sancenón, F. (2018). Smart gated magnetic silica mesoporous particles for targeted colon drug delivery: New approaches for inflammatory bowel diseases treatment. Journal of Controlled Release, 281, 58-69. doi:10.1016/j.jconrel.2018.05.007García-Fernández, A., García-Laínez, G., Ferrándiz, M. L., Aznar, E., Sancenón, F., Alcaraz, M. J., … Orzáez, M. (2017). Targeting inflammasome by the inhibition of caspase-1 activity using capped mesoporous silica nanoparticles. Journal of Controlled Release, 248, 60-70. doi:10.1016/j.jconrel.2017.01.002Rastogi, S. K., Anderson, H. E., Lamas, J., Barret, S., Cantu, T., Zauscher, S., … Betancourt, T. (2017). Enhanced Release of Molecules upon Ultraviolet (UV) Light Irradiation from Photoresponsive Hydrogels Prepared from Bifunctional Azobenzene and Four-Arm Poly(ethylene glycol). ACS Applied Materials & Interfaces, 10(36), 30071-30080. doi:10.1021/acsami.6b16183Martínez-Carmona, M., Lozano, D., Baeza, A., Colilla, M., & Vallet-Regí, M. (2017). A novel visible light responsive nanosystem for cancer treatment. Nanoscale, 9(41), 15967-15973. doi:10.1039/c7nr05050jWeissleder, R. (2001). A clearer vision for in vivo imaging. Nature Biotechnology, 19(4), 316-317. doi:10.1038/86684Jalani, G., Naccache, R., Rosenzweig, D. H., Haglund, L., Vetrone, F., & Cerruti, M. (2016). Photocleavable Hydrogel-Coated Upconverting Nanoparticles: A Multifunctional Theranostic Platform for NIR Imaging and On-Demand Macromolecular Delivery. Journal of the American Chemical Society, 138(3), 1078-1083. doi:10.1021/jacs.5b12357Yan, B., Boyer, J.-C., Branda, N. R., & Zhao, Y. (2011). Near-Infrared Light-Triggered Dissociation of Block Copolymer Micelles Using Upconverting Nanoparticles. Journal of the American Chemical Society, 133(49), 19714-19717. doi:10.1021/ja209793bKnežević, N. Ž., & Lin, V. S.-Y. (2013). A magnetic mesoporous silica nanoparticle-based drug delivery system for photosensitive cooperative treatment of cancer with a mesopore-capping agent and mesopore-loaded drug. Nanoscale, 5(4), 1544. doi:10.1039/c2nr33417hIbsen, S., Zahavy, E., Wrasdilo, W., Berns, M., Chan, M., & Esener, S. (2010). A Novel Doxorubicin Prodrug with Controllable Photolysis Activation for Cancer Chemotherapy. Pharmaceutical Research, 27(9), 1848-1860. doi:10.1007/s11095-010-0183-xPatchornik, A., Amit, B., & Woodward, R. B. (1970). Photosensitive protecting groups. Journal of the American Chemical Society, 92(21), 6333-6335. doi:10.1021/ja00724a041Amit, B., Zehavi, U., & Patchornik, A. (1974). Photosensitive protecting groups of amino sugars and their use in glycoside synthesis. 2-Nitrobenzyloxycarbonylamino and 6-nitroveratryloxycarbonylamino derivatives. The Journal of Organic Chemistry, 39(2), 192-196. doi:10.1021/jo00916a015Bai, X., Li, Z., Jockusch, S., Turro, N. J., & Ju, J. (2003). Photocleavage of a 2-nitrobenzyl linker bridging a fluorophore to the 5’ end of DNA. Proceedings of the National Academy of Sciences, 100(2), 409-413. doi:10.1073/pnas.242729099Laimgruber, S., Schreier, W. J., Schrader, T., Koller, F., Zinth, W., & Gilch, P. (2005). The Photochemistry ofo-Nitrobenzaldehyde as Seen by Femtosecond Vibrational Spectroscopy. Angewandte Chemie International Edition, 44(48), 7901-7904. doi:10.1002/anie.200501642Laimgruber, S., Schreier, W. J., Schrader, T., Koller, F., Zinth, W., & Gilch, P. (2005). Femtosekunden-Schwingungsspektroskopie der Photochemie vono-Nitrobenzaldehyd. Angewandte Chemie, 117(48), 8114-8118. doi:10.1002/ange.200501642Fomina, N., McFearin, C., Sermsakdi, M., Edigin, O., & Almutairi, A. (2010). UV and Near-IR Triggered Release from Polymeric Nanoparticles. Journal of the American Chemical Society, 132(28), 9540-9542. doi:10.1021/ja102595jLin, Q., Huang, Q., Li, C., Bao, C., Liu, Z., Li, F., & Zhu, L. (2010). Anticancer Drug Release from a Mesoporous Silica Based Nanophotocage Regulated by Either a One- or Two-Photon Process. Journal of the American Chemical Society, 132(31), 10645-10647. doi:10.1021/ja103415tAujard, I., Benbrahim, C., Gouget, M., Ruel, O., Baudin, J.-B., Neveu, P., & Jullien, L. (2006). o-Nitrobenzyl Photolabile Protecting Groups with Red-Shifted Absorption: Syntheses and Uncaging Cross-Sections for One- and Two-Photon Excitation. Chemistry - A European Journal, 12(26), 6865-6879. doi:10.1002/chem.200501393Zhao, J., Gover, T. D., Muralidharan, S., Auston, D. A., Weinreich, D., & Kao, J. P. Y. (2006). Caged Vanilloid Ligands for Activation of TRPV1 Receptors by 1- and 2-Photon Excitation†. Biochemistry, 45(15), 4915-4926. doi:10.1021/bi052082fCohanoschi, I., & Hernández, F. E. (2005). Surface Plasmon Enhancement of Two- and Three-Photon Absorption of Hoechst 33 258 Dye in Activated Gold Colloid Solution. The Journal of Physical Chemistry B, 109(30), 14506-14512. doi:10.1021/jp0508958Voliani, V., Ricci, F., Signore, G., Nifosì, R., Luin, S., & Beltram, F. (2011). Multiphoton Molecular Photorelease in Click-Chemistry-Functionalized Gold Nanoparticles. Small, 7(23), 3271-3275. doi:10.1002/smll.201101753Voliani, V., Signore, G., Vittorio, O., Faraci, P., Luin, S., Peréz-Prieto, J., & Beltram, F. (2013). Cancer phototherapy in living cells by multiphoton release of doxorubicin from gold nanospheres. Journal of Materials Chemistry B, 1(34), 4225. doi:10.1039/c3tb20798fLlopis-Lorente, A., de Luis, B., García-Fernández, A., Díez, P., Sánchez, A., Dolores Marcos, M., … Sancenón, F. (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. doi:10.1039/c7tb02045gLlopis-Lorente, A., Díez, P., de la Torre, C., Sánchez, A., Sancenón, F., Aznar, E., … Villalonga, R. (2017). Enzyme-Controlled Nanodevice for Acetylcholine-Triggered Cargo Delivery Based on Janus Au-Mesoporous Silica Nanoparticles. Chemistry - A European Journal, 23(18), 4276-4281. doi:10.1002/chem.201700603Llopis-Lorente, A., de Luis, B., García-Fernández, A., Jimenez-Falcao, S., Orzáez, M., Sancenón, F., … Martínez-Máñez, 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. doi:10.1021/acsami.8b05920Trigari, S., Rindi, A., Margheri, G., Sottini, S., Dellepiane, G., & Giorgetti, E. (2011). Synthesis and modelling of gold nanostars with tunable morphology and extinction spectrum. Journal of Materials Chemistry, 21(18), 6531. doi:10.1039/c0jm04519eSenthil Kumar, P., Pastoriza-Santos, I., Rodríguez-González, B., Javier García de Abajo, F., & Liz-Marzán, L. M. (2007). High-yield synthesis and optical response of gold nanostars. Nanotechnology, 19(1), 015606. doi:10.1088/0957-4484/19/01/015606Guerrero-Martínez, A., Barbosa, S., Pastoriza-Santos, I., & Liz-Marzán, L. M. (2011). Nanostars shine bright for you. Current Opinion in Colloid & Interface Science, 16(2), 118-127. doi:10.1016/j.cocis.2010.12.007Hao, F., Nehl, C. L., Hafner, J. H., & Nordlander, P. (2007). Plasmon Resonances of a Gold Nanostar. Nano Letters, 7(3), 729-732. doi:10.1021/nl062969cAznar, 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/c3cc42210kAznar, E., Marcos, M. D., Martínez-Máñez, R., Sancenón, F., Soto, J., Amorós, P., & Guillem, C. (2009). pH- and Photo-Switched Release of Guest Molecules from Mesoporous Silica Supports. Journal of the American Chemical Society, 131(19), 6833-6843. doi:10.1021/ja810011pKlán, P., Šolomek, T., Bochet, C. G., Blanc, A., Givens, R., Rubina, M., … Wirz, J. (2012). Photoremovable Protecting Groups in Chemistry and Biology: Reaction Mechanisms and Efficacy. Chemical Reviews, 113(1), 119-191. doi:10.1021/cr300177kRittikulsittichai, S., Park, C. S., Marquez, M. D., Jamison, A. C., Frank, T., Wu, C.-H., … Lee, T. R. (2018). Inhibiting Reductive Elimination as an Intramolecular Disulfide Dramatically Enhances the Thermal Stability of SAMs on Gold Derived from Bidentate Adsorbents. Langmuir, 34(23), 6645-6652. doi:10.1021/acs.langmuir.7b0397