Applications of Mesoporous Silica Materials in Food: a Review

[EN] Mesoporous silica materials have been developed for some applications in the health field. These solids are used for the controlled release of bioactive molecules, as catalysts in the synthesis of essential nutrients, as sensors to detect unhealthy products etc., with many applications in food technologies. By combining mesoporous silica materials with food, we can create healthier products, the products that improve our quality of life. The development of mesoporous materials applied to food could result in protecting bioactive molecules during their passage though the digestive system. For this reason, the controlled release of bioactive molecules is a very interesting topic for the discipline of food technology. The use of mesoporous silica supports as catalysts in the synthesis of nutrients and as sensors for the detection of unhealthy products, essential in food, is in great demand industrially for the manufacture of functional foods and films for food and industrial packaging. This review shows some examples of silica materials and their applications in food.Supported by the Ministry of Education, Youth and Sports of the Czech Republic, Project No. MSM C73.Bernardos Bau, A.; Kourimská, L. (2013). Applications of Mesoporous Silica Materials in Food: a Review. Czech Journal of Food Sciences. 31(2):99-107. https://doi.org/10.17221/240/2012-CJFS9910731

Nanotechnology in the Development of Novel Functional Foods or their Package. An Overview Based in Patent Analysis

[EN] In recent years nanotechnology has become a significant component in food industry. It is present in all food chain steps, from the design of new ingredients or additives, to the most modern systems of food quality methods or packaging, demonstrating the great potential of this new technology in a sector as traditional as food. However, while interest by industry in nanotechnology increases, the rejection by consumers, concerned about the potential risk, does too. The aim of this review is to evaluate the development of food nanotechnology by means of a patent analysis, highlighting current applications of nanotechnology along the whole food chain and contextualizing this evolution in the social scene.Financial support from the Spanish Government (project MAT2009-14564-C04-01 and AGL2010-20539) and the Generalitat Valencia (project PROMETEO/2009/016) are gratefully acknowledged. E.P. thanks the Ministerio de Educación for a fellowshipPérez-Esteve, É.; Bernardos Bau, A.; Martínez-Máñez, R.; Barat Baviera, JM. (2013). Nanotechnology in the Development of Novel Functional Foods or their Package. An Overview Based in Patent Analysis. Recent Patents on Food, Nutrition and Agriculture. 5(1):35-43. https://doi.org/10.2174/2212798411305010006S35435

Mesoporous silica materials for controlled delivery based on enzymes

[EN] This review summarises examples of capped mesoporous silica materials for controlled delivery that use enzymes as external triggers or functional components of the gating ensemble.Financial support from the Spanish Government and FEDER funds (Project MAT2015-64139-C4-1) and the Generalitat Valencia (Project PROMETEOII/2014/047) is gratefully acknowledged. A. Llopis-Lorente is grateful to "La Caixa'' Banking Foundation for his PhD fellowship. B. Lozano-Torres is grateful to the Spanish Ministry of Economy and Competitiveness (MEC) for her FPU grant. Also A. Bernardos thanks the Spanish MEC for her Juan de la Cierva Contract.Llopis-Lorente, A.; Lozano-Torres, B.; Bernardos Bau, A.; Martínez-Máñez, R.; Sancenón Galarza, F. (2017). Mesoporous silica materials for controlled delivery based on enzymes. Journal of Materials Chemistry B. 5(17):3069-3083. https://doi.org/10.1039/C7TB00348JS3069308351

Innovative use of essential oil cold diffusion system for improving air quality on indoor cultural heritage spaces

[EN] Bioaerosols play an important role in Cultural Heritage (CH) spaces air quality and biodeterioration risk and there is a growing interest to reduce them in actual conservation strategies. Essential oils (EOs) have been wellknown in several fields for their antimicrobial properties and they have found use in a number of applications. In this work Melaleuca alternifolia (Tea tree) and Thymus vulgaris (Thyme) EOs are cold diffused in unventilated lab spaces for reducing air bacterial and fungi contamination. Moreover, Tea tree EO was also tested in an unventilated real CH space. The effectiveness of EOs in reducing air bacterial and fungi contamination in unventilated indoor spaces during 24 h was evaluated. Air quality was also analyzed by means of temperature, humidity and particulate matter variation. EOs' diffusion system CH artworks risks was studied by means of thermography, diffusion range and EOs compounds deposition on the artistic materials by GC-MS. Tea tree EOs vaporization showed the best results with 77,3% and 95,0% fungi and bacteria air contamination reduction, with no thermohydrometric alteration and absence of EOs components deposition on the artistic vault.The authors wish to thank to the priest of the Santos Juanes Church of Valencia; the 'Direccion General de Patrimonio' and Professor Pilar Roig Picazo; for giving us the permits needed in order to develop this research. We would like to thank to Fundacion Hortensia Herrero, the Spanish Government (projects RTI2018-100910-B-C41 and RTI2018-101599-B-C22-AR (MCUI, FEDER, EU) and A.B. her Beatriz Galindo contract BG20/00020) and the Generalitat Valenciana (project PROM-ETEO 2018/024) for its financial support. Authors wish to thank the collaboration of the Dr. Ignacio Bosch Roig on the thermographic analysis and Dr. Enrique Vivo Soria for the review of the thermohydrometric data.Díaz Alonso, J.; Bernardos Bau, A.; Regidor Ros, JL.; Martínez-Máñez, R.; Bosch-Roig, P. (2021). Innovative use of essential oil cold diffusion system for improving air quality on indoor cultural heritage spaces. International Biodeterioration & Biodegradation. 162:1-10. https://doi.org/10.1016/j.ibiod.2021.10525111016

Mesoporous Silica-Based Materials with Bactericidal Properties

This is the peer reviewed version of the following article: Bernardos, A., Piacenza, E., Sancenón, F., Hamidi, M., Maleki, A., Turner, R. J., Martínez-Máñez, R., Mesoporous Silica-Based Materials with Bactericidal Properties. Small 2019, 15, 1900669. https://doi.org/10.1002/smll.201900669 , which has been published in final form at https://doi.org/10.1002/smll.201900669. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.[EN] Bacterial infections are the main cause of chronic infections and even mortality. In fact, due to extensive use of antibiotics and, then, emergence of antibiotic resistance, treatment of such infections by conventional antibiotics has become a major concern worldwide. One of the promising strategies to treat infection diseases is the use of nanomaterials. Among them, mesoporous silica materials (MSMs) have attracted burgeoning attention due to high surface area, tunable pore/particle size, and easy surface functionalization. This review discusses how one can exploit capacities of MSMs to design and fabricate multifunctional/controllable drug delivery systems (DDSs) to combat bacterial infections. At first, the emergency of bacterial and biofilm resistance toward conventional antimicrobials is described and then how nanoparticles exert their toxic effects upon pathogenic cells is discussed. Next, the main aspects of MSMs (e.g., physicochemical properties, multifunctionality, and biosafety) which one should consider in the design of MSM-based DDSs against bacterial infections are introduced. Finally, a comprehensive analysis of all the papers published dealing with the use of MSMs for delivery of antibacterial chemicals (antimicrobial agents functionalized/adsorbed on mesoporous silica (MS), MS-loaded with antimicrobial agents, gated MS-loaded with antimicrobial agents, MS with metal-based nanoparticles, and MS-loaded with metal ions) is provided.The authors thank the Spanish Government (projects MAT2015-64139-C4-1-R and AGL2015-70235-C2-2-R (MINECO/FEDER)) and the Generalitat Valenciana (project PROMETEOII/2014/047 and PROMETEO/2018/024) for support. A.B. thanks the Spanish Government for her Juan de la Cierva incorporacion contract IJCI-2014-21534.Bernardos Bau, A.; Piacenza, E.; Sancenón Galarza, F.; Hamidi, M.; Maleki, A.; Turner, R.; Martínez-Máñez, R. (2019). Mesoporous Silica-Based Materials with Bactericidal Properties. Small. 15(24):1-34. https://doi.org/10.1002/smll.201900669S134152

Nutritional effects of folic acid controlled release from mesoporous materials

[EN] Folic acid deficiency causes serious disorders in humans and supplementation has numerous health benefits. However, there is initial evidence that suggest a negative impact of an increased exposure to folic with respect to certain developmental and degenerative disorders. In this line, controlled release of folic acid by using mesoporous silica materials, MCM-41, has been studied as an alternative to direct supplementation. For this purpose, various mesoporous solids MCM-41 loaded with folic acid (S1) and functionalized with 3-[2-(2-aminoethylamino)ethylamino]propyl-trimethoxysilane (S2) acting as "gate" have been tested. The results show that at pH 2 a strongly hindered vitamin release is observed, whereas at pH 7.5 a controlled delivery is found. Based on the obtained results of this study, folic acid controlled release could be feasible during a period of 5h using a sensitive to pH gate, and this might reduce traditional fortification negative effects, while nutritional benefits are maintainedBarat Baviera, JM.; Pérez-Esteve, É.; Bernardos Bau, A.; Martínez-Máñez, R. (2011). Nutritional effects of folic acid controlled release from mesoporous materials. Procedia Food Science. 1:1828-1832. doi:10.1016/j.profoo.2011.09.268S18281832

Surfactant-Triggered Molecular Gate Tested on Different Mesoporous Silica Supports for Gastrointestinal Controlled Delivery

[EN] In recent decades, the versatility of mesoporous silica particles and their relevance to develop controlled release systems have been demonstrated. Within them, gated materials able to modulate payload delivery represent great advantages. However, the role played by the porous matrix in this kind of systems is scarce. In this work, different mesoporous silica materials (MCM-41, MCM-48, SBA-15 and UVM-7) are functionalized with oleic acid as a molecular gate. All systems are fully characterized and their ability to confine the entrapped cargo and release it in the presence of bile salts is validated with release assays and in vitro digestion experiments. The cargo release profile of each synthesized support is studied, paying attention to the inorganic scaffold. Obtained release profiles fit to Korsmeyer-Peppas model, which explains the differences among the studied supports. Based on the results, UVM-7 material was the most appropriate system for duodenal delivery and was tested in an in vivo model of the Wistar rat. Payload confinement and its complete release after gastric emptying is achieved, establishing the possible use of mesoporous silica particles as protection and direct release agents into the duodenum and, hence, demonstrating that these systems could serve as an alternative to the administration methods employed until now.This research was funded by the Spanish Government (projects RTI2018-100910-B-C41 and RTI2018-101599-B-C22-AR (MCUI/FEDER, EU)) and the Generalitat Valenciana (project PROMETEO/2018/024 and ACIF/2016/023 grant).Poyatos-Racionero, E.; González-Álvarez, I.; González-Álvarez, M.; Martínez-Máñez, R.; Marcos Martínez, MD.; Bernardos Bau, A.; Aznar, E. (2020). Surfactant-Triggered Molecular Gate Tested on Different Mesoporous Silica Supports for Gastrointestinal Controlled Delivery. Nanomaterials. 10(7):1-18. https://doi.org/10.3390/nano10071290S118107Pérez-Esteve, É., Ruiz-Rico, M., de la Torre, C., Llorca, E., Sancenón, F., Marcos, M. D., … Barat, J. M. (2016). Stability of different mesoporous silica particles during an in vitro digestion. Microporous and Mesoporous Materials, 230, 196-207. doi:10.1016/j.micromeso.2016.05.004Di Pasqua, A. J., Sharma, K. K., Shi, Y.-L., Toms, B. B., Ouellette, W., Dabrowiak, J. C., & Asefa, T. (2008). Cytotoxicity of mesoporous silica nanomaterials. Journal of Inorganic Biochemistry, 102(7), 1416-1423. doi:10.1016/j.jinorgbio.2007.12.028Izquierdo-Barba, I., Colilla, M., Manzano, M., & Vallet-Regí, M. (2010). In vitro stability of SBA-15 under physiological conditions. Microporous and Mesoporous Materials, 132(3), 442-452. doi:10.1016/j.micromeso.2010.03.025Arruebo, M. (2011). Drug delivery from structured porous inorganic materials. WIREs Nanomedicine and Nanobiotechnology, 4(1), 16-30. doi:10.1002/wnan.132Vallet-Regí, M., Balas, F., & Arcos, D. (2007). Mesoporous Materials for Drug Delivery. Angewandte Chemie International Edition, 46(40), 7548-7558. doi:10.1002/anie.200604488Descalzo, 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.200600734Shang, L., Bian, T., Zhang, B., Zhang, D., Wu, L.-Z., Tung, C.-H., … Zhang, T. (2013). Graphene-Supported Ultrafine Metal Nanoparticles Encapsulated by Mesoporous Silica: Robust Catalysts for Oxidation and Reduction Reactions. Angewandte Chemie International Edition, 53(1), 250-254. doi:10.1002/anie.201306863Taguchi, A., & Schüth, F. (2005). Ordered mesoporous materials in catalysis. Microporous and Mesoporous Materials, 77(1), 1-45. doi:10.1016/j.micromeso.2004.06.030Bernardos, A., Marina, T., Žáček, P., Pérez-Esteve, É., Martínez-Mañez, R., Lhotka, M., … Klouček, P. (2014). Antifungal effect of essential oil components against Aspergillus niger when loaded into silica mesoporous supports. Journal of the Science of Food and Agriculture, 95(14), 2824-2831. doi:10.1002/jsfa.7022Barat, J., Pérez-Esteve, É., Bernardos, A., & Martínez-Mañez, R. (2011). Nutritional effects of folic acid controlled release from mesoporous materials. Procedia Food Science, 1, 1828-1832. doi:10.1016/j.profoo.2011.09.268Ruiz-Rico, M., Daubenschüz, H., Pérez-Esteve, É., Marcos, M. D., Amorós, P., Martínez-Máñez, R., & Barat, J. M. (2016). Protective effect of mesoporous silica particles on encapsulated folates. European Journal of Pharmaceutics and Biopharmaceutics, 105, 9-17. doi:10.1016/j.ejpb.2016.05.016Mas, N., Arcos, D., Polo, L., Aznar, E., Sánchez-Salcedo, S., Sancenón, F., … Martínez-Máñez, R. (2014). Towards the Development of Smart 3D «Gated Scaffolds» for On-Command Delivery. Small, 10(23), 4859-4864. doi:10.1002/smll.201401227Bernardos, A., Piacenza, E., Sancenón, F., Hamidi, M., Maleki, A., Turner, R. J., & Martínez‐Máñez, R. (2019). Mesoporous Silica‐Based Materials with Bactericidal Properties. Small, 15(24), 1900669. doi:10.1002/smll.201900669Santos-Figueroa, L. E., Giménez, C., Agostini, A., Aznar, E., Marcos, M. D., Sancenón, F., … Amorós, P. (2013). Selective and Sensitive Chromofluorogenic Detection of the Sulfite Anion in Water Using Hydrophobic Hybrid Organic-Inorganic Silica Nanoparticles. Angewandte Chemie International Edition, 52(51), 13712-13716. doi:10.1002/anie.201306688Poyatos-Racionero, E., Ros-Lis, J. V., Vivancos, J.-L., & Martínez-Máñez, R. (2018). Recent advances on intelligent packaging as tools to reduce food waste. Journal of Cleaner Production, 172, 3398-3409. doi:10.1016/j.jclepro.2017.11.075Coll, C., Casasús, R., Aznar, E., Marcos, M. D., Martínez-Máñez, R., Sancenón, F., … Amorós, P. (2007). Nanoscopic hybrid systems with a polarity-controlled gate-like scaffolding for the colorimetric signalling of long-chain carboxylates. Chem. Commun., (19), 1957-1959. doi:10.1039/b617703dPerez-Esteve, E., Bernardos, A., Martinez-Manez, R., & M. Barat, J. (2013). Nanotechnology in the Development of Novel Functional Foods or their Package. An Overview Based in Patent Analysis. Recent Patents on Food, Nutrition & Agriculture, 5(1), 35-43. doi:10.2174/2212798411305010006Lamprecht, A., Schäfer, U., & Lehr, C. (2001). Pharmaceutical Research, 18(6), 788-793. doi:10.1023/a:1011032328064Awaad, A., Nakamura, M., & Ishimura, K. (2012). Imaging of size-dependent uptake and identification of novel pathways in mouse Peyer’s patches using fluorescent organosilica particles. Nanomedicine: Nanotechnology, Biology and Medicine, 8(5), 627-636. doi:10.1016/j.nano.2011.08.009Hussain, N. (2001). Recent advances in the understanding of uptake of microparticulates across the gastrointestinal lymphatics. Advanced Drug Delivery Reviews, 50(1-2), 107-142. doi:10.1016/s0169-409x(01)00152-1Fu, C., Liu, T., Li, L., Liu, H., Chen, D., & Tang, F. (2013). The absorption, distribution, excretion and toxicity of mesoporous silica nanoparticles in mice following different exposure routes. Biomaterials, 34(10), 2565-2575. doi:10.1016/j.biomaterials.2012.12.043ALOthman, Z. (2012). A Review: Fundamental Aspects of Silicate Mesoporous Materials. Materials, 5(12), 2874-2902. doi:10.3390/ma5122874Asefa, T., & Tao, Z. (2012). Mesoporous silica and organosilica materials — Review of their synthesis and organic functionalization. Canadian Journal of Chemistry, 90(12), 1015-1031. doi:10.1139/v2012-094Li, Y., Li, N., Pan, W., Yu, Z., Yang, L., & Tang, B. (2017). Hollow Mesoporous Silica Nanoparticles with Tunable Structures for Controlled Drug Delivery. ACS Applied Materials & Interfaces, 9(3), 2123-2129. doi:10.1021/acsami.6b13876Legnoverde, M. S., & Basaldella, E. I. (2016). Influence of particle size on the adsorption and release of cephalexin encapsulated in mesoporous silica SBA-15. Materials Letters, 181, 331-334. doi:10.1016/j.matlet.2016.06.053Popova, M., Szegedi, A., Mavrodinova, V., Novak Tušar, N., Mihály, J., Klébert, S., … Yoncheva, K. (2014). Preparation of resveratrol-loaded nanoporous silica materials with different structures. Journal of Solid State Chemistry, 219, 37-42. doi:10.1016/j.jssc.2014.07.002Martín, A., Morales, V., Ortiz-Bustos, J., Pérez-Garnes, M., Bautista, L. F., García-Muñoz, R. A., & Sanz, R. (2018). 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New Oleic Acid-Capped Mesoporous Silica Particles as Surfactant-Responsive Delivery Systems

[EN] A new delivery microdevice, based on hydrophobic oleic acid¿capped mesoporous silica particles and able to payload release in the presence of surfactants, has been developed. The oleic acid functionalization confers to the system a high hydrophobic character, which avoids cargo release unless surfactant molecules are present. The performance of this oleic¿acid capped microdevice in the presence of different surfactants is presented and its zero¿release operation in the absence of surfactants is demonstrated.The authors want to thank the Spanish Government (projects MAT2015-64139-C4-1-R, AGL2015-70235-C2-1-R and AGL2015-70235-C2-2-R (MINECO/FEDER)) and RTI2018-100910-B-C41, RTI2018-101599-B-C22 and RTI2018-101599-B-C21 (MCUI/AEI/FEDER, UE)) and Generalitat Valenciana (project PROMETEO/2018/024) for support. E.P.-R. thanks the Generalitat Valenciana for her predoctoral fellowship. 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Preclinical antitumor efficacy of senescence-inducing chemotherapy combined with a nanoSenolytic

[EN] The induction of senescence produces a stable cell cycle arrest in cancer cells, thereby inhibiting tumor growth; however, the incomplete immune cell-mediated clearance of senescent cells may favor tumor relapse, limiting the long-term anti-tumorigenic effect of such drugs. A combination of senescence induction and the elimination of senescent cells may, therefore, represent an efficient means to inhibit tumor relapse. In this study, we explored the antitumor efficacy of a combinatory senogenic and targeted senolytic therapy in an immunocompetent orthotopic mouse model of the aggressive triple negative breast cancer subtype. Following palbociclib-induced senogenesis and senolysis by treatment with nano-encapsulated senolytic agent navitoclax, we observed inhibited tumor growth, reduced metastases, and a reduction in the systemic toxicity of navitoclax. We believe that this combination treatment approach may have relevance to other senescence-inducing chemotherapeutic drugs and additional tumor types. Significance: While the application of senescence inducers represents a successful treatment strategy in breast cancer patients, some patients still relapse, perhaps due to the subsequent accumulation of senescent cells in the body that can promote tumor recurrence. We now demonstrate that a combination treatment of a senescence inducer and a senolytic nanoparticle selectively eliminates senescent cells, delays tumor growth, and reduces metastases in a mouse model of aggressive breast cancer. Collectively, our results support targeted senolysis as a new therapeutic opportunity to improve outcomes in breast cancer patients.The M.O. laboratory members thank the financial support from the Spanish Government (project SAF2017-84689-R (MINECO/AEI/FEDER, EU)) and the Generalitat Valenciana (project PROMETEO/2019/065). The R.M. laboratory members thank the financial support from the Spanish Government (projects RTI2018-100910-B-C41 and RTI2018-101599-B-C22 (MCUI/FEDER, EU) and the Generalitat Valenciana (project PROMETEO 2018/024). Both I.G. and B.L-T. are grateful to the Generalitat Valenciana and the Spanish Ministry of Economy, respectively, for their Ph.D. grants. I.G. would like to thank I. Borreda and J. Forteza and the Instituto Valenciano de Patologia for their special collaboration and F. Sancenon for his appreciated helpGaliana, I.; Lozano-Torres, B.; Sancho, M.; Alfonso-Navarro, M.; Bernardos Bau, A.; Bisbal, V.; Serrano, M.... (2020). Preclinical antitumor efficacy of senescence-inducing chemotherapy combined with a nanoSenolytic. Journal of Controlled Release. 323:624-634. https://doi.org/10.1016/j.jconrel.2020.04.045S624634323Hernandez-Segura, A., Nehme, J., & Demaria, M. (2018). Hallmarks of Cellular Senescence. 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Enhanced antimicrobial activity of essential oil components immobilized on silica particles

[EN] The antimicrobial activity of essential oils components (EOCs) is well-known. However, their high volatility and powerful aroma limit their application in the formulation of a wide range of food products. In this context, the antimicrobial activity of carvacrol, eugenol, thymol and vanillin grafted onto the surface of three silica supports with different morphologies, textural properties and chemical reactivities (fumed silica, amorphous silica and MCM-41) was evaluated herein. Materials characterization revealed a good immobilization yield and all the devices showed a micro-scale particle size. Sensory evaluation revealed that sensory perception of EOCs decreases after covalent immobilization. Moreover, immobilization greatly enhanced the antimicrobial activity of the essential oil components against Listeria innocua and Escherichia coli compared to free components. The incorporation of EOCs immobilized on silica particles into pasteurized milk inoculated with L. innocua demonstrated their effectiveness not only for in vitro conditions, but also in a real food system.Authors gratefully acknowledge the financial support from the Ministerio de Economia, Industria y Competitividad and FEDER funds (Projects AGL2015-70235-C2-1-R, AGL2015-70235-C2-2-R and MAT2015-64139-C4-1-R (MINECO/FEDER)) and the Generalitat Valenciana (Project PROMETEOII/2014/047). M.R.R. is grateful to the Ministerio de Education, Cultura y Deporte for her grant (AP2010-4369). The authors also thank the Electron Microscopy Service at the UPV for support.Ruiz Rico, M.; Pérez-Esteve, É.; Bernardos Bau, A.; Sancenón Galarza, F.; Martínez-Máñez, R.; Marcos Martínez, MD.; Barat Baviera, JM. (2017). Enhanced antimicrobial activity of essential oil components immobilized on silica particles. Food Chemistry. 233:228-236. https://doi.org/10.1016/j.foodchem.2017.04.118S22823623