Few, but convincing words in the work of Mendes da Rocha

La extensa producción arquitectónica de Mendes da Rocha resulta difícil de clasificar bajo el reduccionismo de los ‘ismos’ porque supone una revisión crítica y de síntesis de una modernidad replanteada. Se abordan tres aproximaciones al conjunto de su obra. Primera: la nueva tradición moderna de la arquitectura brasileña atendiendo a la implicación urbana de sus obras y a la escala de intervención (objeto, contexto, territorio). Segunda: la simbiosis entre arte y técnica desde una poética que tiende a la reducción de los elementos y a la simbolización de arquetipos. Tercera: la relativa al modo en que el maestro se enfrenta a las obras de intervención en el patrimonio recurriendo a una estética de la pobreza. Pocas, pero contundentes palabras: sencillez y humildad como atributos de la rotundidad.The extensive architectural production of Mendes da Rocha is difficult to classify under the reductionism of the ‘isms’ since it involves a reevaluation and a synthesis of a reviewed modernity. Three approaches are addressed to his work. First: the new modern tradition of Brazilian architecture, considering the urban implications of their work and the scale of intervention (object, context, territory). Second: the symbiosis between art and technology from a poetry that tends to reduce the elements and the symbolization of archetypes. Third, relative to how the master faces the works of intervention works in the patrimony using aesthetics of poverty. Few, but convincing words: simplicity and humility as attributes of the convincing nature

Environmental assessment model for scrubbers versus alternative mitigation systems for feeder vessels in liner shipping

[Abstract] Implementation of the Global Sulphur Cap (GSC), in January 2020, boosted scrubber installation in vessels to fulfill the new air emission limitations. This increase in scrubbers’ use has intensified concern about its environmental performance. Even though achievement of GSC requirements through this mitigation system has been widely proven, the impact of wash water discharge on the marine environment remains under discussion. In this paper, an assessment environmental model is introduced to quantify in monetary terms the performance of feeder vessels that operate with several mitigation systems. This model attempts to improve traditional air emission evaluations by including the impact of scrubbers’ discharges on the marine environmental. In this way, the analysis not only allows different mitigations systems to be ranked by considering their capacity to reduce air emissions, but also provides further information about the marine eutrophication and ecotoxicity impact from scrubbers’ discharge. Through the model’s application to a regular shipping line between the Canary Islands and the Iberian Peninsula, it was found that, the scrubber, regardless of its operation mode (open- or closed loop), is the most efficient mitigation option after the Liquefied Natural Gas (LNG) fuel shift. The impact of scrubbers’ discharge was not as significant as expected on the feeder vessel’s total pollution since this provides similar relative weight to the methane emissions from a dual-engine option by operating with LNG. The results also show the need to more closely research the marine eutrophication impact of closed-loop scrubbers. Finally, this paper warns about a significant dispersion on the monetary values of marine ecotoxicity and eutrophication, due to a high dependence of the results on the frameworks’ localization. Consequently, further research is needed on the homogenization of pollution monetization in the marine environment

Environmental inefficiencies of short sea shipping vessels by optimization processes based on resistance prediction methods

[Abstract]: Fulfilment of the progressive environmental normative involves a singular challenge for Short Sea Shipping (SSS), since it must maintain its competitiveness versus other transport alternatives. For this reason, over the last decade SSS vessels have been the subject of numerous analyses, in terms of operative research, and optimizations, from the marine engineering standpoint. Despite widespread awareness about the impact of a vessel’s resistance on environmental performance, many of the previous analyses were based on resistance prediction methods with low accuracy levels. This fact necessarily involves deviations regarding the expected sustainability of vessels. This paper attempts to quantify (in monetary terms) the environmental consequences due to this low level of accuracy. To meet this aim, it analyzes the environmental performance of an SSS feeder vessel, which was obtained from an optimization process based on standard resistance prediction techniques, when its propulsion power requirements for sailing at optimized speed were assessed through the Reynolds Averaged Navier–Stokes method in Computational Fluid Dynamic simulations. The findings show that standard resistance prediction methods without consideration of hull shape must be avoided, not only in the optimization process, but also for operative research, especially in free sailing analysis

Tradition, technology and heritage in the works of Mendes da Rocha

La producción de Mendes da Rocha se suele enmarcar dentro del ‘regionalismo crítico’ ante la revisión del canon moderno del siglo XX. En este artículo se abordan tres aspectos de su arquitectura: tradición, técnica y patrimonio. El primero sitúa su obra como heredera de la praxis moderna brasileña preocupada por la configuración del espacio público; esta perspectiva permite entender su trabajo bajo el prisma de una creciente implicación urbana: la arquitectura como objeto, la arquitectura como entorno y la arquitectura como territorio. El segundo explora el énfasis puesto por Mendes en el par arte-técnica, empleando una poética de reducción de elementos y de simbolización de arquetipos que encuentra en el hormigón armado el léxico para la nueva sintaxis de la modernidad. Y el tercero desgrana el modo en que aborda la intervención en el patrimonio con una estética ‘puritana’, singularizada por estrategias sustractivas: intervenir también consiste en suprimir lo innecesario.The production of Mendes da Rocha is usually framed within ‘critical regionalism’ regarding the review of modern architectural canon in the twentieth century. Three aspects of his architecture are discussed here: tradition, technique and heritage. The first aspect sets his work as heir of modern Brazilian architecture concerned by the configuration of the public space. This outlook allows to understand his work under a growing urban concern: architecture as an object, architecture as part of the surroundings and architecture on the territorial scale. The second aspect explores the emphasis given by Mendes to the couple art-technique, developing a poetic based on the reduction of elements and the symbolization of archetypes which finds in reinforced concrete the appropriate lexicon for the new syntax of modernity. The third aspect reflects on the way he addresses his work in built heritage with a ‘puritan’ aesthetic singularised by subtractive strategies: designing may also imply suppressing the unnecessary

Effect of Dietary Coenzyme Q10 Plus NADH Supplementation on Fatigue Perception and Health-Related Quality of Life in Individuals with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Prospective, Randomized, Double-Blind, Placebo-Controlled Trial

Coenzima Q10; Mitocondrias; Encefalomielitis miálgicaCoenzyme Q10; Mitochondria; Myalgic encephalomyelitisCoenzim Q10; Mitocondris; Encefalomielitis miàlgicaMyalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex, multisystem, and profoundly debilitating neuroimmune disease, probably of post-viral multifactorial etiology. Unfortunately, no accurate diagnostic or laboratory tests have been established, nor are any universally effective approved drugs currently available for its treatment. This study aimed to examine whether oral coenzyme Q10 and NADH (reduced form of nicotinamide adenine dinucleotide) co-supplementation could improve perceived fatigue, unrefreshing sleep, and health-related quality of life in ME/CFS patients. A 12-week prospective, randomized, double-blind, placebo-controlled trial was conducted in 207 patients with ME/CFS, who were randomly allocated to one of two groups to receive either 200 mg of CoQ10 and 20 mg of NADH (n = 104) or matching placebo (n = 103) once daily. Endpoints were simultaneously evaluated at baseline, and then reassessed at 4- and 8-week treatment visits and four weeks after treatment cessation, using validated patient-reported outcome measures. A significant reduction in cognitive fatigue perception and overall FIS-40 score (p < 0.001 and p = 0.022, respectively) and an improvement in HRQoL (health-related quality of life (SF-36)) (p < 0.05) from baseline were observed within the experimental group over time. Statistically significant differences were also shown for sleep duration at 4 weeks and habitual sleep efficiency at 8 weeks in follow-up visits from baseline within the experimental group (p = 0.018 and p = 0.038, respectively). Overall, these findings support the use of CoQ10 plus NADH supplementation as a potentially safe therapeutic option for reducing perceived cognitive fatigue and improving the health-related quality of life in ME/CFS patients. Future interventions are needed to corroborate these clinical benefits and also explore the underlying pathomechanisms of CoQ10 and NADH administration in ME/CFS.J.C.-M. received financial support and honoraria from Vitae Health Innovation Co., S.L. (Montmeló, Barcelona, Spain). This study was partially supported by the Vall d’Hebron Hospital Research Institute (Barcelona, Spain). Vitae Health Innovation Co. supplied both treatments (Coenzyme Q10 and NADH supplement tablets and placebo)

Blood donation attitudes and knowledge in Spanish undergraduates with roles in health-education

Recent investigations highlight how important it is to identify the key factors involved in the design of strategies to promote blood donation among undergraduates as a public health concern. The study aims to investigate attitudes and knowledge towards blood donation in university students with health education roles and examine the way sociodemographic and educational characteristics play a part in it. Materials and methods: A cross-sectional and multi-center design was used. A structured questionnaire was answered by 1128 Spanish university students (Schools of Health Sciences and Education Sciences). Results: The knowledge test indicated a low score (M = 4.2 out of 10), being Me = 3.00 in the case of Education Sciences and Me = 5.00 in Health Sciences students. The greatest degree of importance is found in the “external incentives” dimension (M = 3.7 out of 5). Health science students and participants with relatives who needed a donation showed fewer “fears” (p ≤ 0.001) and “pretexts” (p ≤ 0.01). Conclusions: The low knowledge score stresses the need to develop valuable health education-related strategies in the curriculum of studies related with health education; showing room for improvement particularly in Education Science students. Health education interventions aimed at increasing donors in the university environment should be designed while considering differences among undergraduates. Based on their better attitudes, health science students might play a relevant role in promoting blood donationS

Real-Time In Vivo Detection of Cellular Senescence through the Controlled Release of the NIR Fluorescent Dye Nile Blue

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.202004142S15152151565935He, S., & Sharpless, N. E. (2017). Senescence in Health and Disease. Cell, 169(6), 1000-1011. doi:10.1016/j.cell.2017.05.015Lozano-Torres, B., Estepa-Fernández, A., Rovira, M., Orzáez, M., Serrano, M., Martínez-Máñez, R., & Sancenón, F. (2019). The chemistry of senescence. Nature Reviews Chemistry, 3(7), 426-441. doi:10.1038/s41570-019-0108-0Muñoz-Espín, D., & Serrano, M. (2014). Cellular senescence: from physiology to pathology. Nature Reviews Molecular Cell Biology, 15(7), 482-496. doi:10.1038/nrm3823Hernandez-Segura, A., Nehme, J., & Demaria, M. (2018). Hallmarks of Cellular Senescence. Trends in Cell Biology, 28(6), 436-453. doi:10.1016/j.tcb.2018.02.001Baker, D. J., Childs, B. G., Durik, M., Wijers, M. E., Sieben, C. J., Zhong, J., … van Deursen, J. M. (2016). Naturally occurring p16Ink4a-positive cells shorten healthy lifespan. Nature, 530(7589), 184-189. doi:10.1038/nature16932Soto-Gamez, A., & Demaria, M. (2017). Therapeutic interventions for aging: the case of cellular senescence. Drug Discovery Today, 22(5), 786-795. doi:10.1016/j.drudis.2017.01.004Kirkland, J. L., Tchkonia, T., Zhu, Y., Niedernhofer, L. J., & Robbins, P. D. (2017). The Clinical Potential of Senolytic Drugs. Journal of the American Geriatrics Society, 65(10), 2297-2301. doi:10.1111/jgs.14969Niedernhofer, L. J., & Robbins, P. D. (2018). Senotherapeutics for healthy ageing. Nature Reviews Drug Discovery, 17(5), 377-377. doi:10.1038/nrd.2018.44Hayflick, L., & Moorhead, P. S. (1961). The serial cultivation of human diploid cell strains. Experimental Cell Research, 25(3), 585-621. doi:10.1016/0014-4827(61)90192-6Zhang, R., & Adams, P. D. (2007). Heterochromatin and its Relationship to Cell Senescence and Cancer Therapy. Cell Cycle, 6(7), 784-789. doi:10.4161/cc.6.7.4079Campisi, J. (2005). Senescent Cells, Tumor Suppression, and Organismal Aging: Good Citizens, Bad Neighbors. Cell, 120(4), 513-522. doi:10.1016/j.cell.2005.02.003Dimri, G. P., Lee, X., Basile, G., Acosta, M., Scott, G., Roskelley, C., … Pereira-Smith, O. (1995). A biomarker that identifies senescent human cells in culture and in aging skin in vivo. Proceedings of the National Academy of Sciences, 92(20), 9363-9367. doi:10.1073/pnas.92.20.9363Lozano-Torres, B., Galiana, I., Rovira, M., Garrido, E., Chaib, S., Bernardos, A., … Sancenón, F. (2017). An OFF–ON Two-Photon Fluorescent Probe for Tracking Cell Senescence in Vivo. Journal of the American Chemical Society, 139(26), 8808-8811. doi:10.1021/jacs.7b04985Asanuma, D., Sakabe, M., Kamiya, M., Yamamoto, K., Hiratake, J., Ogawa, M., … Urano, Y. (2015). Sensitive β-galactosidase-targeting fluorescence probe for visualizing small peritoneal metastatic tumours in vivo. Nature Communications, 6(1). doi:10.1038/ncomms7463Muñoz-Espín, D. (2019). Nanocarriers targeting senescent cells. Translational Medicine of Aging, 3, 1-5. doi:10.1016/j.tma.2019.01.001Ekpenyong-Akiba, A. E., Canfarotta, F., Abd H., B., Poblocka, M., Casulleras, M., Castilla-Vallmanya, L., … Macip, S. (2019). Detecting and targeting senescent cells using molecularly imprinted nanoparticles. Nanoscale Horizons, 4(3), 757-768. doi:10.1039/c8nh00473kAlberti, 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/c4cc10414eDe la Torre, C., Casanova, I., Acosta, G., Coll, C., Moreno, M. J., Albericio, F., … Martínez-Máñez, R. (2014). Gated Mesoporous Silica Nanoparticles Using a Double-Role Circular Peptide for the Controlled and Target-Preferential Release of Doxorubicin in CXCR4-Expresing Lymphoma Cells. Advanced Functional Materials, 25(5), 687-695. doi:10.1002/adfm.201403822Bernardos, 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.200900880Agostini, 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.201204663Muñoz‐Espín, D., Rovira, M., Galiana, I., Giménez, C., Lozano‐Torres, B., Paez‐Ribes, M., … Serrano, M. (2018). A versatile drug delivery system targeting senescent cells. EMBO Molecular Medicine, 10(9). doi:10.15252/emmm.201809355Mérian, J., Gravier, J., Navarro, F., & Texier, I. (2012). Fluorescent Nanoprobes Dedicated to in Vivo Imaging: From Preclinical Validations to Clinical Translation. Molecules, 17(5), 5564-5591. doi:10.3390/molecules17055564Fu, W., Yan, C., Guo, Z., Zhang, J., Zhang, H., Tian, H., & Zhu, W.-H. (2019). Rational Design of Near-Infrared Aggregation-Induced-Emission-Active Probes: In Situ Mapping of Amyloid-β Plaques with Ultrasensitivity and High-Fidelity. Journal of the American Chemical Society, 141(7), 3171-3177. doi:10.1021/jacs.8b12820Ovchinnikov, O. V., Evtukhova, A. V., Kondratenko, T. S., Smirnov, M. S., Khokhlov, V. Y., & Erina, O. V. (2016). Manifestation of intermolecular interactions in FTIR spectra of methylene blue molecules. Vibrational Spectroscopy, 86, 181-189. doi:10.1016/j.vibspec.2016.06.016Aznar, 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.5b00456Llopis-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/c7tb00348jGarcía‐Fernández, A., Aznar, E., Martínez‐Máñez, R., & Sancenón, F. (2019). New Advances in In Vivo Applications of Gated Mesoporous Silica as Drug Delivery Nanocarriers. Small, 16(3), 1902242. doi:10.1002/smll.201902242Kozlovskaya, V., Xue, B., & Kharlampieva, E. (2016). Shape-Adaptable Polymeric Particles for Controlled Delivery. Macromolecules, 49(22), 8373-8386. doi:10.1021/acs.macromol.6b01740Mishra, D. K., Shandilya, R., & Mishra, P. K. (2018). Lipid based nanocarriers: a translational perspective. Nanomedicine: Nanotechnology, Biology and Medicine, 14(7), 2023-2050. doi:10.1016/j.nano.2018.05.021Seidi, F., Jenjob, R., Phakkeeree, T., & Crespy, D. (2018). Saccharides, oligosaccharides, and polysaccharides nanoparticles for biomedical applications. Journal of Controlled Release, 284, 188-212. doi:10.1016/j.jconrel.2018.06.026Chen, W., Zhou, S., Ge, L., Wu, W., & Jiang, X. (2018). Translatable High Drug Loading Drug Delivery Systems Based on Biocompatible Polymer Nanocarriers. Biomacromolecules, 19(6), 1732-1745. doi:10.1021/acs.biomac.8b00218Vázquez-González, M., & Willner, I. (2018). DNA-Responsive SiO2 Nanoparticles, Metal–Organic Frameworks, and Microcapsules for Controlled Drug Release. Langmuir, 34(49), 14692-14710. doi:10.1021/acs.langmuir.8b00478Farid, R. M., Youssef, N. A. H. A., & Kassem, A. A. (2018). Platform for Lipid Based Nanocarriers’ Formulation Components and their Potential Effects: A Literature Review. Current Pharmaceutical Design, 23(43), 6613-6629. doi:10.2174/1381612824666171128104814Lombardo, D., Calandra, P., Barreca, D., Magazù, S., & Kiselev, M. (2016). Soft Interaction in Liposome Nanocarriers for Therapeutic Drug Delivery. Nanomaterials, 6(7), 125. doi:10.3390/nano6070125Bansal, A., & Zhang, Y. (2014). Photocontrolled Nanoparticle Delivery Systems for Biomedical Applications. Accounts of Chemical Research, 47(10), 3052-3060. doi:10.1021/ar500217wKamaly, N., Yameen, B., Wu, J., & Farokhzad, O. C. (2016). Degradable Controlled-Release Polymers and Polymeric Nanoparticles: Mechanisms of Controlling Drug Release. Chemical Reviews, 116(4), 2602-2663. doi:10.1021/acs.chemrev.5b00346Trewyn, B. G., Slowing, I. I., Giri, S., Chen, H.-T., & Lin, V. S.-Y. (2007). Synthesis and Functionalization of a Mesoporous Silica Nanoparticle Based on the Sol–Gel Process and Applications in Controlled Release. Accounts of Chemical Research, 40(9), 846-853. doi:10.1021/ar600032

Au-Mesoporous silica nanoparticles gated with disulfide-linked oligo(ethylene glycol) chains for tunable cargo delivery mediated by an integrated enzymatic control unit

[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/c7tb02045gS6734673953

Vacunació de les dones embarassades contra la tos ferina a Catalunya

Vacunació; Dones embarassades; Tos ferinaVacunación; Mujeres embarazadas; Tos ferinaVaccination; Pregnant women; Whooping CoughDocument que parla sobre l'epidemiologia de la tos ferina a Catalunya i proporciona recomanacions sobre la vacunació en dones embarassades per protegir el nadó els primers mesos de vida

Electro-responsive films containing voltage responsive gated mesoporous silica nanoparticles grafted onto PEDOT-based conducting polymer

[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 PROMETEO2018-024) for support.García-Fernández, A.; Lozano-Torres, B.; Blandez, JF.; Monreal-Trigo, J.; Soto Camino, J.; Collazos-Castro, JE.; Alcañiz Fillol, M.... (2020). Electro-responsive films containing voltage responsive gated mesoporous silica nanoparticles grafted onto PEDOT-based conducting polymer. Journal of Controlled Release. 323:421-430. https://doi.org/10.1016/j.jconrel.2020.04.048S421430323Aznar, 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.5b00456Mura, S., Nicolas, J., & Couvreur, P. (2013). Stimuli-responsive nanocarriers for drug delivery. Nature Materials, 12(11), 991-1003. doi:10.1038/nmat3776Llopis-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/c7tb00348jTarn, D., Ashley, C. E., Xue, M., Carnes, E. C., Zink, J. I., & Brinker, C. J. (2013). Mesoporous Silica Nanoparticle Nanocarriers: Biofunctionality and Biocompatibility. Accounts of Chemical Research, 46(3), 792-801. doi:10.1021/ar3000986Mauriello Jimenez, C., Aggad, D., Croissant, J. G., Tresfield, K., Laurencin, D., Berthomieu, D., … Durand, J.-O. (2018). Porous Porphyrin-Based Organosilica Nanoparticles for NIR Two-Photon Photodynamic Therapy and Gene Delivery in Zebrafish. Advanced Functional Materials, 28(21), 1800235. doi:10.1002/adfm.201800235Alberti, 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/c4cc10414eLlopis-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.8b05920Yang, P., Gai, S., & Lin, J. (2012). Functionalized mesoporous silica materials for controlled drug delivery. Chemical Society Reviews, 41(9), 3679. doi:10.1039/c2cs15308dSong, N., & Yang, Y.-W. (2015). Molecular and supramolecular switches on mesoporous silica nanoparticles. Chemical Society Reviews, 44(11), 3474-3504. doi:10.1039/c5cs00243eOroval, M., Díez, P., Aznar, E., Coll, C., Marcos, M. D., Sancenón, F., … Martínez-Máñez, R. (2016). Self-Regulated Glucose-Sensitive Neoglycoenzyme-Capped Mesoporous Silica Nanoparticles for Insulin Delivery. Chemistry - A European Journal, 23(6), 1353-1360. doi:10.1002/chem.201604104De 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.201704161Llopis-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/ncomms15511Pascual, L., Baroja, I., Aznar, E., Sancenón, F., Marcos, M. D., Murguía, J. R., … Martínez-Máñez, R. (2015). Oligonucleotide-capped mesoporous silica nanoparticles as DNA-responsive dye delivery systems for genomic DNA detection. Chemical Communications, 51(8), 1414-1416. doi:10.1039/c4cc08306gArgyo, C., Weiss, V., Bräuchle, C., & Bein, T. (2013). Multifunctional Mesoporous Silica Nanoparticles as a Universal Platform for Drug Delivery. Chemistry of Materials, 26(1), 435-451. doi:10.1021/cm402592tLi, 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/c1cs15246gKumar, P., Tambe, P., Paknikar, K. M., & Gajbhiye, V. (2018). Mesoporous silica nanoparticles as cutting-edge theranostics: Advancement from merely a carrier to tailor-made smart delivery platform. Journal of Controlled Release, 287, 35-57. doi:10.1016/j.jconrel.2018.08.024Lai, 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., Zhao, X., Wu, T., & Feng, P. (2008). Tunable Redox-Responsive Hybrid Nanogated Ensembles. Journal of the American Chemical Society, 130(44), 14418-14419. doi:10.1021/ja8060886Qu, H., Yang, L., Yu, J., Dong, T., Rong, M., Zhang, J., … Liu, H. (2017). A redox responsive controlled release system using mesoporous silica nanoparticles capped with Au nanoparticles. RSC Advances, 7(57), 35704-35710. doi:10.1039/c7ra04444eGiménez, C., de la Torre, C., Gorbe, M., Aznar, E., Sancenón, F., Murguía, J. R., … Amorós, P. (2015). Gated Mesoporous Silica Nanoparticles for the Controlled Delivery of Drugs in Cancer Cells. Langmuir, 31(12), 3753-3762. doi:10.1021/acs.langmuir.5b00139Luo, Z., Hu, Y., Cai, K., Ding, X., Zhang, Q., Li, M., … Zhao, Y. (2014). Intracellular redox-activated anticancer drug delivery by functionalized hollow mesoporous silica nanoreservoirs with tumor specificity. Biomaterials, 35(27), 7951-7962. doi:10.1016/j.biomaterials.2014.05.058Du, X., Xiong, L., Dai, S., Kleitz, F., & Qiao, S. Z. (2014). Intracellular Microenvironment-Responsive Dendrimer-Like Mesoporous Nanohybrids for Traceable, Effective, and Safe Gene Delivery. Advanced Functional Materials, 24(48), 7627-7637. doi:10.1002/adfm.201402408Raza, A., Hayat, U., Rasheed, T., Bilal, M., & Iqbal, H. M. N. (2018). Redox-responsive nano-carriers as tumor-targeted drug delivery systems. European Journal of Medicinal Chemistry, 157, 705-715. doi:10.1016/j.ejmech.2018.08.034Xiao, Y., Wang, T., Cao, Y., Wang, X., Zhang, Y., Liu, Y., & Huo, Q. (2015). Enzyme and voltage stimuli-responsive controlled release system based on β-cyclodextrin-capped mesoporous silica nanoparticles. Dalton Transactions, 44(9), 4355-4361. doi:10.1039/c4dt03758hWang, T., Sun, G., Wang, M., Zhou, B., & Fu, J. (2015). Voltage/pH-Driven Mechanized Silica Nanoparticles for the Multimodal Controlled Release of Drugs. ACS Applied Materials & Interfaces, 7(38), 21295-21304. doi:10.1021/acsami.5b05619Jiao, X., Sun, R., Cheng, Y., Li, F., Du, X., Wen, Y., … Zhang, X. (2017). A Voltage-Responsive Free-Blockage Controlled-Release System Based on Hydrophobicity Switching. ChemPhysChem, 18(10), 1317-1323. doi:10.1002/cphc.201700117Khashab, N. M., Trabolsi, A., Lau, Y. A., Ambrogio, M. W., Friedman, D. C., Khatib, H. A., … Stoddart, J. F. (2009). Redox- and pH-Controlled Mechanized Nanoparticles. European Journal of Organic Chemistry, 2009(11), 1669-1673. doi:10.1002/ejoc.200801300Guimard, N. K., Gomez, N., & Schmidt, C. E. (2007). Conducting polymers in biomedical engineering. Progress in Polymer Science, 32(8-9), 876-921. doi:10.1016/j.progpolymsci.2007.05.012Wang, X., Zhi, L., & Müllen, K. (2007). Transparent, Conductive Graphene Electrodes for Dye-Sensitized Solar Cells. Nano Letters, 8(1), 323-327. doi:10.1021/nl072838rLeigh, S. J., Bradley, R. J., Purssell, C. P., Billson, D. R., & Hutchins, D. A. (2012). A Simple, Low-Cost Conductive Composite Material for 3D Printing of Electronic Sensors. PLoS ONE, 7(11), e49365. doi:10.1371/journal.pone.0049365Zhang, D., Ryu, K., Liu, X., Polikarpov, E., Ly, J., Tompson, M. E., & Zhou, C. (2006). Transparent, Conductive, and Flexible Carbon Nanotube Films and Their Application in Organic Light-Emitting Diodes. Nano Letters, 6(9), 1880-1886. doi:10.1021/nl0608543Kenry, & Liu, B. (2018). Recent Advances in Biodegradable Conducting Polymers and Their Biomedical Applications. Biomacromolecules, 19(6), 1783-1803. doi:10.1021/acs.biomac.8b00275Palza, H., Zapata, P., & Angulo-Pineda, C. (2019). Electroactive Smart Polymers for Biomedical Applications. Materials, 12(2), 277. doi:10.3390/ma12020277Naseri, M., Fotouhi, L., & Ehsani, A. (2018). Recent Progress in the Development of Conducting Polymer-Based Nanocomposites for Electrochemical Biosensors Applications: A Mini-Review. The Chemical Record, 18(6), 599-618. doi:10.1002/tcr.201700101Inal, S., Rivnay, J., Suiu, A.-O., Malliaras, G. G., & McCulloch, I. (2018). Conjugated Polymers in Bioelectronics. Accounts of Chemical Research, 51(6), 1368-1376. doi:10.1021/acs.accounts.7b00624Aqrawe, Z., Montgomery, J., Travas-Sejdic, J., & Svirskis, D. (2017). Conducting Polymers as Electrode Coatings for Neuronal Multi-electrode Arrays. Trends in Biotechnology, 35(2), 93-95. doi:10.1016/j.tibtech.2016.06.007Vara, H., & Collazos-Castro, J. E. (2015). Biofunctionalized Conducting Polymer/Carbon Microfiber Electrodes for Ultrasensitive Neural Recordings. ACS Applied Materials & Interfaces, 7(48), 27016-27026. doi:10.1021/acsami.5b09594Green, R., & Abidian, M. R. (2015). Conducting Polymers for Neural Prosthetic and Neural Interface Applications. Advanced Materials, 27(46), 7620-7637. doi:10.1002/adma.201501810Svirskis, D., Travas-Sejdic, J., Rodgers, A., & Garg, S. (2010). Electrochemically controlled drug delivery based on intrinsically conducting polymers. Journal of Controlled Release, 146(1), 6-15. doi:10.1016/j.jconrel.2010.03.023Uppalapati, D., Boyd, B. J., Garg, S., Travas-Sejdic, J., & Svirskis, D. (2016). Conducting polymers with defined micro- or nanostructures for drug delivery. Biomaterials, 111, 149-162. doi:10.1016/j.biomaterials.2016.09.021Alves-Sampaio, A., García-Rama, C., & Collazos-Castro, J. E. (2016). Biofunctionalized PEDOT-coated microfibers for the treatment of spinal cord injury. Biomaterials, 89, 98-113. doi:10.1016/j.biomaterials.2016.02.037Guo, B., & Ma, P. X. (2018). Conducting Polymers for Tissue Engineering. Biomacromolecules, 19(6), 1764-1782. doi:10.1021/acs.biomac.8b00276Wadhwa, R., Lagenaur, C. F., & Cui, X. T. (2006). Electrochemically controlled release of dexamethasone from conducting polymer polypyrrole coated electrode. Journal of Controlled Release, 110(3), 531-541. doi:10.1016/j.jconrel.2005.10.027Shamaeli, E., & Alizadeh, N. (2014). Nanostructured biocompatible thermal/electrical stimuli-responsive biopolymer-doped polypyrrole for controlled release of chlorpromazine: Kinetics studies. International Journal of Pharmaceutics, 472(1-2), 327-338. doi:10.1016/j.ijpharm.2014.06.036Esrafilzadeh, D., Razal, J. M., Moulton, S. E., Stewart, E. M., & Wallace, G. G. (2013). Multifunctional conducting fibres with electrically controlled release of ciprofloxacin. Journal of Controlled Release, 169(3), 313-320. doi:10.1016/j.jconrel.2013.01.022Richardson, R. T., Wise, A. K., Thompson, B. C., Flynn, B. O., Atkinson, P. J., Fretwell, N. J., … Clark, G. M. (2009). Polypyrrole-coated electrodes for the delivery of charge and neurotrophins to cochlear neurons. Biomaterials, 30(13), 2614-2624. doi:10.1016/j.biomaterials.2009.01.015Boehler, C., Kleber, C., Martini, N., Xie, Y., Dryg, I., Stieglitz, T., … Asplund, M. (2017). Actively controlled release of Dexamethasone from neural microelectrodes in a chronic in vivo study. Biomaterials, 129, 176-187. doi:10.1016/j.biomaterials.2017.03.019Collazos-Castro, J. E., Polo, J. L., Hernández-Labrado, G. R., Padial-Cañete, V., & García-Rama, C. (2010). Bioelectrochemical control of neural cell development on conducting polymers. Biomaterials, 31(35), 9244-9255. doi:10.1016/j.biomaterials.2010.08.057Cho, Y., Shi, R., Ivanisevic, A., & Ben Borgens, R. (2009). A mesoporous silica nanosphere-based drug delivery system using an electrically conducting polymer. Nanotechnology, 20(27), 275102. doi:10.1088/0957-4484/20/27/275102García-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.2017.01.002Lozano-Torres, B., Pascual, L., Bernardos, A., Marcos, M. D., Jeppesen, J. O., Salinas, Y., … Sancenón, F. (2017). Pseudorotaxane capped mesoporous silica nanoparticles for 3,4-methylenedioxymethamphetamine (MDMA) detection in water. Chemical Communications, 53(25), 3559-3562. doi:10.1039/c7cc00186jCollazos-Castro, J. E., Hernández-Labrado, G. R., Polo, J. L., & García-Rama, C. (2013). N-Cadherin- and L1-functionalised conducting polymers for synergistic stimulation and guidance of neural cell growth. Biomaterials, 34(14), 3603-3617. doi:10.1016/j.biomaterials.2013.01.097Garcia-Breijo, E., Peris, R. M., Pinatti, C. O., Fillol, M. A., Civera, J. I., & Prats, R. B. (2013). Low-Cost Electronic Tongue System and Its Application to Explosive Detection. IEEE Transactions on Instrumentation and Measurement, 62(2), 424-431. doi:10.1109/tim.2012.2215156Orgill, J. J., Chen, C., Schirmer, C. R., Anderson, J. L., & Lewis, R. S. (2015). Prediction of methyl viologen redox states for biological applications. Biochemical Engineering Journal, 94, 15-21. doi:10.1016/j.bej.2014.11.005Zhang, L. (2010). Glycosaminoglycan (GAG) Biosynthesis and GAG-Binding Proteins. Glycosaminoglycans in Development, Health and Disease, 1-17. doi:10.1016/s1877-1173(10)93001-9Collazos-Castro, J. E., García-Rama, C., & Alves-Sampaio, A. (2016). Glial progenitor cell migration promotes CNS axon growth on functionalized electroconducting microfibers. Acta Biomaterialia, 35, 42-56. doi:10.1016/j.actbio.2016.02.023Ito, M., & Kuwana, T. (1971). Spectroelectrochemical study of indirect reduction of triphosphopyridine nucleotide. Journal of Electroanalytical Chemistry and Interfacial Electrochemistry, 32(3), 415-425. doi:10.1016/s0022-0728(71)80144-4Nezakati, T., Seifalian, A., Tan, A., & Seifalian, A. M. (2018). Conductive Polymers: Opportunities and Challenges in Biomedical Applications. Chemical Reviews, 118(14), 6766-6843. doi:10.1021/acs.chemrev.6b00275Vitale, F., Summerson, S. R., Aazhang, B., Kemere, C., & Pasquali, M. (2015). Neural Stimulation and Recording with Bidirectional, Soft Carbon Nanotube Fiber Microelectrodes. ACS Nano, 9(4), 4465-4474. doi:10.1021/acsnano.5b0106