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[EN] Synthetic cathinones are a class of new psychoactive substances whose consumption has increased a lot and is widespread throughout the world. Thus, there is currently a need for rapid and simple detection of these drugs. In particular, detection of synthetic cathinones in oral fluid in drivers can be of great importance in preventing traffic accidents. Herein, we report two probes, based on BODIPY derivatives combined with Cu(ii), which are able to detect these drugs both in water and in oral fluid, by changes in color and fluorescence. The determined limits of detection for ephedrone (as a model drug) are lower than the usual concentrations in saliva after intake of this type of drug. The sensing mechanism seems to be related to the cathinone induced reduction of Cu(ii) to Cu(i) with concomitants changes in the BODIPY structure., We thank the Spanish Government, MCIN/AEI/10.13039/501100011033 and "ERDF A way of making Europe" (fund RTL2018-100910-B-C42), the Spanish Ministry of Health, Consumer Affairs and Social Welfare (Project 2020I040 PNSD 2020) and Generalitat Valenciana (PROMETEO 2018/024) for financial support. SCSIE (Universitat de Valencia) is gratefully acknowledged for all the equipment employed. NMR was registered at the U26 facility of ICTS "NAMBIOSIS" at the Universitat of Valencia.

[EN] The Fluorescence sensing technique for trace detection of High Energy Materials (HEMs) has gained more attention in recent times. In the present paper, the interaction between the fluorophore and HEMs is studied using spectroscopic and electrochemical techniques. The fluorophore polyaniline (PANI) was functionalised by doping it with benzenesulfonic acid (BSA) to increase the processability, and mobility of ¿-electrons along with decreased ¿-stacking. It is observed that upon doping the solubility of BSA-PANI is increased, facilitating a higher quenching by commercial explosives, i.e., RDX, CL-20, CL-20:RDX cocrystal. The interaction studies undertaken though fluorescence quenching, FTIR and Resonance Raman studies shows that the benzenoid unit, polaron and bipolaron nitrogen in BSA-PANI interact with nitro groups of HEMs and form a charge-transfer complex between HEMs and BSA-PANI undergoing predominantly a PET mechanism. LOD value is found to be least for Cocrystal (1.876¿×¿10¿5 M) when compared to other HEMs 3.191¿×¿10¿5 M (CL-20), 5.904¿×¿10¿5 M (RDX), 3.734¿×¿10¿5 M (PETN) indicating that cocrystal can be detected in trace level. The collaborative study between cyclic voltammetry and the observed results of fluorescence quenching, revealed that the emeraldine salt form of (BSA-PANI) is sensitive to HEMs., The authors acknowledge and thank Prof. G. U. Kulkarni, the former Director of Centre for Nano and Soft Matter (CeNS) for providing the facility to work in the centre. The authors, S A Ture and V B Patil, expresses their thanks to M/s Premier Explosive Limited for their Financial support (H/A: 4254), the corresponding author expresses his thanks to UGC, New Delhi for the BSR faculty fellowship [F.4-5(11)/2019(BSR)]. We also thank the Spanish Government [RTI2018-100910-B-C41 (MCUI/AEI/FEDER, UE)] and Generalitat Valenciana (PROMETEO2018/024) for their support.

[EN] Many anticancer agents used in clinics induce premature senescence in healthy tissues generating accelerated aging processes and adverse side-effects in patients. Cardiotoxicity is a well-known limiting factor of anticancer treatment with doxorubicin (DOX), a very effective anthracycline widely used as antitumoral therapy in clinical practice, that leads to long-term morbidity and mortality. DOX exposure severely affects the population of cardiac cells in both mice and human hearts by inducing premature senescence, which may represent the molecular basis of DOX-induced cardiomyopathy. Here, we demonstrate that senescence induction in the heart contributes to impaired cardiac function in mice upon DOX treatment. Concomitant elimination of senescent cells with the senolytic Navitoclax in different formulations produces a significant decrease in senescence and cardiotoxicity markers together with the restoration of the cardiac function in mice followed by echocardiography. These results evidence the potential clinical use of senolytic therapies to alleviate cardiotoxicities induced in chemotherapy-treated patients., 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). M.O. thanks the financial support from the Spanish Government project (PID2020-115048RB-I00) and the Generalitat Valenciana (project PROMETEO/2019/065). A. L-V. is grateful to the Instituto de Salud Carlos III for her Ph.D. i-PFIS grant (IFI17/00039). A.E-F. and B.L.-T thanks to the Spanish Government for their Ph.D. grant (FPU17/05454) and (FPU15/02707). J.B. thanks to the Instituto de Salud Carlos III for his Sara Borrell contract (CD19/00038). M.A. thanks her postdoctoral fellowship (PAID-10-17). The funders had no role in the design, data collection, decision to publish, or preparation of the manuscript. The authors thank Alberto Hernandez for confocal microscopy, Alicia Martinez for flow cytometry, and Laura Ramirez for genomics guidance. The authors thank for the use of Biorender.com.

Background and objective: Hyperthermia is a cancer treatment aiming to induce cell death by directly warming cancerous tissues above 40 °C. This technique can be applied both individually and together with other cancer therapies. The main challenge for researchers and medics is to heat only tumoral cells avoiding global or localized heating of sane tissues. The objective in this study is to provide a realistic virtual scenario to develop an optimized multi-site injection plan for tailored magnetic nanoparticle-mediated hyperthermia applications. Methods: A three-dimensional model of a cat's back was tested in three different simulation scenarios, showing the impact of magnetic nanoparticles in each specific environment configuration. Results: As a result of this study. This simulation method can, minimising the affection to healthy tissue. Conclusions: This virtual method will help real and personalized therapy planning and tailor the dose and distribution of magnetic nanoparticles for an enhanced hyperthermia cancer treatment., Computer Methods and Programs in Biomedicine, 226, ISSN:0169-2607, ISSN:1872-7565

[EN] beta-Galactosidase (beta-Gal) is a widely used enzyme as a reporter gene in the field of molecular biology which hydrolyzes the beta-galactosides into monosaccharides. beta-Gal is an essential enzyme in humans and its deficiency or its overexpression results in several rare diseases. Cellular senescence is probably one of the most relevant physiological disorders that involve beta-Gal enzyme. In this review, we assess the progress made to date in the design of molecular-based probes for the detection of beta-Gal both in vitro and in vivo. Most of the reported molecular probes for the detection of beta-Gal consist of a galactopyranoside residue attached to a signalling unit through glycosidic bonds. The beta-Gal-induced hydrolysis of the glycosidic bonds released the signalling unit with remarkable changes in color and/or emission. Additional examples based on other approaches are also described. The wide applicability of these probes for the rapid and in situ detection of de-regulation beta-Gal-related diseases has boosted the research in this fertile field, R.M laboratory members received the financial support from the Spanish Government (project RTI2018-100910-B-C41) and the Generalitat Valenciana (project PROMETEO 2018/024). B.L-T. received support from the Spanish Ministry of Economy for their PhD grants (FPU15/02707). J. F.-B received fellowship (CD19/00038)

[EN] Celiac disease is a complex and autoimmune disorder caused by the ingestion of gluten affecting almost 1% of global population. Nowadays an effective treatment does not exist, and the only way to manage the disease is the removal of gluten from the diet. Owing the key role played by gluten, clear and regulated labelling of foodstuff and smart methods for gluten detection are needed to fight frauds on food industry and to avoid the involuntary ingestion of this protein by celiac patients. On that scope, the development of a novel detection system of gluten is here presented. The sensor consists of nanoporous anodic alumina films loaded with a fluorescent dye and capped with an aptamer that recognizes gliadin (gluten's soluble proteins). In the presence of gliadin, aptamer sequences displace from the surface of anodic alumina resulting in pore opening and dye delivery. The dispositive shows a limit of detection (LOD) of 100 mu g kg(-1) of gliadin, good selectivity and a detection time of approximately 60 min. Moreover, the sensor is validated in real food samples. This novel probe allows fast gluten detection through a simple signalling process with potential use for food control. (C) 2020 Elsevier B.V. All rights reserved., The authors want to thank the Spanish Government RTI2018-100910-B-C41 (MCUI/AEI/FEDER, UE) and the Generalitat Valenciana (project PROMETEO/2018/024) for support. L.P. thanks to Ministerio de Economia, Industria y Competitividad for his FPI grant. S.S.-F. thanks CIBER and ISCIII for her Sara Borrell contract. The authors also thank the Electron Microscopy Service at the UPV for support.

[EN] Introduction: Breast cancer has the highest mortality rate among cancers in women. Patients suffering from certain breast cancers, such as triple-negative breast cancer (TNBC), lack effective treatments. This represents a clinical concern due to the associated poor prognosis and high mortality. As an approach to succeed over conventional therapy limitations, we present herein the design and evaluation of a novel nanodevice based on enzyme-functionalized gold nanoparticles to efficiently perform enzyme prodrug therapy (EPT) in breast cancer cells. Results: In particular, the enzyme horseradish peroxidase (HRP) which oxidizes the prodrug indole-3-acetic acid (IAA) to release toxic oxidative species is incorporated on gold nanoconjugates (HRP-AuNCs), obtaining an efficient nanoplatform for EPT. The nanodevice is biocompatible and effectively internalized by breast cancer cell lines. Remarkably, co-treatment with HRP-AuNCs and IAA (HRP-AuNCs/IAA) reduces the viability of breast cancer cells below 5%. Interestingly, 3D tumor models (multicellular tumor spheroid-like cultures) co-treated with HRP-AuNCs/IAA exhibit a 74% reduction of cell viability, whereas the free formulated components (HRP, IAA) have no effect. Conclusion: Altogether, our results demonstrate that the designed HRP-AuNCs nanoformulation shows a remarkable therapeutic performance. These findings might help to bypass the clinical limitations of current tumor enzyme therapies and advance towards the use of nanoformulations for EPT in breast cancer., Gema Vivo-Llorca thanks the Generalitat Valenciana for her fellowship ACIF/2017/072. Paula Díez thanks the Generalitat Valenciana for her contract APOSTD/2020/153 and to the Instituto de Salud Carlos III and the European Social Fund for the financial support "Sara Borrell", CD20/00120. Antoni Llopis-Lorente thanks funding from the European Union¿s Horizon 2020 research and innovation programme under grant agreement No 847675. Images were prepared using Servier Medical Art (https://smart.servier.com/). We thank the Spanish Government (project RTI2018-100910-B-C41 (MCUI/AEI/FEDER, UE); SAF2017-84689-R-B (MCUI/ AEI/FEDER, UE)) and the Generalitat Valenciana (project PROMETEO/2018/024 and PROMETEO/2019/065) for support. A pre-print version of this work was published as a chapter of the PhD thesis of the first author Gema VivoLlorca

[EN] Cage compounds offer unique binding pockets similar to enzyme-binding sites, which can be customized in terms of size, shape, and functional groups to point toward the cavity and many other parameters. Different synthetic strategies have been developed to create a toolkit of methods that allow preparing tailor-made organic cages for a number of distinct applications, such as gas separation, molecular recognition, molecular encapsulation, hosts for catalysis, etc. These examples show the versatility and high selectivity that can be achieved using cages, which is impossible by employing other molecular systems. This review explores the progress made in the field of fully organic molecular cages and containers by focusing on the properties of the cavity and their application to encapsulate guests., V.M.-C. acknowledges the financial support from project CIDEGENT/2020/031 funded by the Generalitat Valenciana and project PID2020-113256RA-I00 funded by MCIN/AEI/10.13039/501100011033. R.M.-M. and F.S. acknowledge the financial support from project PROMETEO 2018/024 from the Generalitat Valenciana and project RTI2018-100910-B-C41 funded by MCIN/AEI/10.13039/501100011033/and FEDER A way to make Europe. Funding for open access charge: CRUE-Universitat Politecnica de Valencia.

[EN] We report herein the design of a strip-based rapid test utilizing bio-inspired hybrid nanomaterials for the in situ and at site detection of the drug scopolamine (SCP) using a smartphone for readout, allowing SCP identification in diluted saliva down to 40 nM in less than 15 min. For this purpose, we prepared a nanosensor based on mesoporous silica nanoparticles loaded with a fluorescent reporter (rhodamine B) and functionalized with bethanechol, a potent agonist of recombinant human muscarinic acetylcholine receptor M-2 (M-2-AChR). M-2-AChR interaction with the anchored bethanechol derivative leads to capping of the pores. The sensing mechanism relies on binding of SCP to M-2-AChR resulting in pore opening and delivery of the entrapped rhodamine B reporter. Moreover, the material was incorporated into strips for lateral-flow assays coupled to smartphone readout, giving fast response time, good selectivity, and exceptional sensitivity. In an attempt to a mobile analytical test system for law enforcement services, we have also developed a dualplex lateral flow assay for SCP and 3,4-methylenedioxypyrovalerone (MDPV) also known as the so-called "cannibal drug"., This research was funded by the Ministerio de Ciencia, Innovacion y Universidades (Spanish Government), the Agencia Estatal de Investigacion (AEI), the European Union (projects RTI2018-100910-B-C41 and RTI2018-101599-B-C22-AR (MCIU/AEI/FEDER, EU), the Conselleria de Innovacion, Universidades, Ciencia y Sociedad Digital, Generalitat Valenciana (Project PROMETEO 2018/024) and the German Research Foundation (DFG; CL 761/1-19). E. G. is grateful to the Spanish MEC for her FPU grant (FPU16/02464).

[EN] A new method for senescent cell detection is described, which is based on lipofuscin labeling with a fluorescent reporter through a biorthogonal strain-promoted azide-alkyne cycloaddition. The sensing protocol involves a first step where the interaction of lipofuscin with a Sudan Black B derivative containing an azide moiety (SBB-N3 ) is carried out. In the final step, the azide moiety reacts with a fluorophore containing a cyclooctene ring (BODIPY). The efficacy of this two-step protocol is assessed in senescent melanoma SK-MEL-103 cells, senescent triple-negative breast cancer MDA-MB-231 cells and senescent WI-38 fibroblasts. In all cases, a clear fluorescence pattern was observed in senescent cells, compared to proliferative cells, only when the SBB-N3 -BODIPY probe was formed. Our results provide an alternative tool for the detection of senescent cells, based on an in situ bio-orthogonal reaction for lipofuscin labeling, RM laboratory members are grateful for financial support from the FEDER foundation of European Union (IDIFEDER/2021/044), the Spanish Government (projects RTI2018-100910-B-C41 and RTI2018-101599-B-C22) and the Generalitat Valenciana (project PROMETEO 2018/024). BL-T and AG-F acknowledge their current Margarita Salas postdoctoral fellowship from UPV-MIU and 'Next Generation EU' program. JF-B is grateful for his Sara Borrell postdoctoral fellowship (CD19/00038).

[EN] In this work, the optimization of the immunochemical response of antibody-gated indicator delivery (gAID) systems prepared with mesoporous silica nanoparticles has been studied along various lines of system tailoring, targeting the peroxide-type explosive TATP as an exemplary analyte. The mechanism of detection of these gAID systems relies on a displacement of an antibody "cap" bound to hapten derivatives anchored to the surface of a porous hybrid material, allowing the indicator cargo stored in the mesopores to escape and massively amplify the analyte-related signal. Since our aim was to obtain gAID systems with the best possible response in terms of sensitivity, selectivity, and assay time, sera obtained from different immunization boosts were screened, the influence of auxiliary reagents was assessed, structural hapten modification (hapten heterology) was investigated, and various indicator dyes and host materials were tested. Considering that highly selective and sensitive immunological responses are best obtained with highaffinity antibodies which, however, could possess rather slow dissociation constants, leading to slow responses, the main challenge was to optimize the immunochemical recognition system for a rapid response while maintaining a high sensitivity and selectivity. The best performance was observed by grafting a slightly mismatching (heterologous) hapten to the surface of the nanoparticles in combination with high-affinity antibodies as "caps", yielding for the first time gAID nanomaterials for which the response time could be improved from hours to, This research was funded by the German Research Foundation (DFG; CL 761/1-19), the Spanish Government (project RTI2018-100910-B-C41 (MCUI/FEDER, EU)), and the Generalitat Valenciana (project PROMETEO 2018/024).

6 pags., 4 figs., We have established an easy synthetic protocol for selectively developing all-orthogonal BODIPY trimers with unprecedented geometries on the basis of selecting methyl oxidation versus electrophilic formylation of key dimeric precursors. Photophysical characterization together with biological assays unraveled the most suitable BODIPY-BODIPY geometrical arrangements within the trimer, forcing them to serve as molecular platforms for the development of new, advanced heavy-atom-free photosensitizers for photodynamic therapy and phototheragnosis., The authors acknowledge Spanish MICINN (PID2020-11455GB-C31, -C32, and -C33 and RTI2018-100910-BC41), Spanish Instituto de Salud Carlos III (IFI19/00026), Gobierno Vasco (IT1639-22), and Generalitat Valenciana (PROMETEO 2018/024) for financial support. A.P.-C. thanks Comunidad de Madrid for a research contract. C.D.-N. thanks MICINN for a FPI contract. B.E.-N. thanks the IFI19/00026 project, which is co-funded by the European Union, for a research contract.

[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.

[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 help

[EN] Conducting Polymers (CPs), in recent times have contributed significantly in the detection of High Energy Materials possessing nitro functional groups through fluorescence quenching studies. Camphor sulphuric acid doped polyaniline (C-PANI) is studied with a view to obtain easily processable PANI without pi-stacking for the detection of Picric acid(PA) and p-nitro toluene(pNT) in trace levels. The quenching constant and limit of detection were found to be 2.236x10(-6) M and 6.14x10(-7) M for PA and 1.9447x10(-7) M and 3.57x10(-7) M for pNT, respectively showing a very good sensitivity in detection. Resonance Raman spectroscopy (RRS) showed the involvement of the bipolaronic and benzenoid group in the charge transfer complex formed between the conducting polymer and the analyte. The photoluminescence studies indicated a predominant PET mechanism. The electrochemical studies employing cyclic voltammetry gave higher band gap on comparison with absorption studies. The positive and negative shift in oxidation and reduction potential of polymer-analyte was observed and collaborated with the fluorescence studies to understand the possible fluorescence quenching mechanism from electrochemical approach., The authors greatly acknowledge and thank Prof. G. U. Kulkarni, the Director of Centre for Nano and Soft Matter (CeNS) for providing the facility to work in the centre. Specifically, one of our author, Satish Ashok Ture, expresses his thanks to M/s Premier Explosive Limited for their Financial support (H/A: 4254). We also thank the Spanish Government (RTI2018-100910-B-C41 (MCUI/AEI/FEDER, UE)) and Generalitat Valenciana (PROMETEO2018/024) for their support. Part of this work is carried out under the Gulbarga University-Central University of Karnataka MoU program.

[EN] Essential oil components (EOCs) such as eugenol play a significant role in plant antimicrobial defense. Due to the volatility and general reactivity of these molecules, plants have evolved smart systems for their storage and release, which are key prerequisites for their efficient use. In this study, biomimetic systems for the controlled release of eugenol, inspired by natural plant defense mechanisms, were prepared and their antifungal activity is described. Delivery and antifungal studies of mesoporous silica nanoparticles (MSN) loaded with eugenol and capped with different saccharide gates-starch, maltodextrin, maltose and glucose-against fungus Aspergillus niger-were performed. The maltodextrin- and maltose-capped systems show very low eugenol release in the absence of the fungus Aspergillus niger but high cargo delivery in its presence. The anchored saccharides are degraded by exogenous enzymes, resulting in eugenol release and efficient inhibition of fungal growth., This research was funded by the project NutRisk (Project No: CZ.02.1.01/0.0/0.0/16_019/0000845), the Spanish Government (projects RTI2018-100910-B-C41, RTI2018-101599-B-C22-AR and RTI2018-101599-B-C21-AR (MINECO/FEDER)) and the GeneralitatValenciana (project PROME-TEO 2018/024); by the National Agency for Agricultural Research of the Ministry of Agriculture of the Czech Republic under project Biostore QK21010064; and by the Research Infrastructure METROFOOD-CZ supported by the Ministry of Education, Youth, and Sports of the Czech Republic under project number LM201810. A.B. thanks the Spanish Government for financial support.

[EN] The development of new food preservatives is essential to prevent foodborne outbreaks or food spoilage due to microbial growth, enzymatic activity or oxidation. Furthermore, new compounds that substitute the commonly used synthetic food preservatives are needed to stifle the rising problem of microbial resistance. In this scenario, we report herein, as far as we know, for the first time the use of the zein protein as a gating moiety and its application for the controlled release of essential oil components (EOCs). The design of microdevices consist of mesoporous silica particles loaded with essential oils components (thymol, carvacrol and cinnamaldehyde) and functionalized with the zein (prolamin) protein found in corn as a molecular gate. The zein protein grafted on the synthesized microdevices is degraded by the proteolytic action of bacterial enzymatic secretions with the consequent release of the loaded essential oil components efficiently inhibiting bacterial growth. The results allow us to conclude that the new microdevice presented here loaded with the essential oil component cinnamaldehyde improved the antimicrobial properties of the free compound by decreasing volatility and increasing local concentration., This research was funded by the Government of Spain (projects RTI2018-100910-B-C41, RTI2018-101599-B-C22-AR and RTI2018-101599-B-C21-AR (MCUI/FEDER, EU)) and the Generalitat Valenciana (project PROMETEO 2018/024, grant numbers ACIF/2016/023 and APOSTD/2019/118).

[EN] The construction of communication models at the micro¿/nanoscale involving abiotic nanodevices and living organisms has the potential to open a wide range of applications in biomedical and communication technologies. However, this area remains almost unexplored. Herein, we report, as a proof of concept, a stimuli¿responsive interactive paradigm of communication between yeasts (as a model microorganism) and enzyme¿controlled Janus Au¿mesoporous silica nanoparticles. In the presence of the stimulus, the information flows from the microorganism to the nanodevice, and then returns from the nanodevice to the microorganism as a feedback., B.dL. is grateful to the Spanish Government for her FPU PhD fellowship. The authors wish to thank the Spanish Government (projects RTI2018-100910-B-C41 (MCUI/AEI/FEDER, UE) and CTQ2017-87954-P), the Generalitat Valenciana (project PROMETEO2018/024), the Comunidad de Madrid (Project IND2017/BMD-7642) and CIBER-BBN (NANOCOM project) for support.

[EN] Here we describe the construction of an integrated and pH-sensitive nanomachine with layer-by-layer supramolecular design and enzymatic control for on-command delivery. The nanodevice comprises a first layer of ß-cyclodextrin-coated gold nanoparticles as capping element of benzimidazole functionalized mesoporous silica nanoparticles, and a second control layer based on an adatamantane-modified glucose oxidase derivative. The nanomachine was selectively fuelled by glucose and successfully employed for the autonomous release of doxorubicin in HeLa cancer cells., Financial support from the Spanish Ministry of Economy and Competitiveness (projects CTQ2014-58989-P, CTQ2015-71936-REDT, CTQ2017-87954-P, and MAT2015-64139-C4-1-R) and generalitat Valenciana (project PROMETEO/2018/024) is gratefully acknowledged.

[EN] A nanodevice based on mesoporous silica nanoparticles with rhodamine B in the pore framework, functionalized with carboxylates on the outer surface and capped with the cationic polymyxin B peptide, was used to selectively detect endotoxin in aqueous solutions with a limit of detection in the picomolar range., The authors thank the Spanish Government (MAT2015 64139-C4-1-R) and the Generalitat Valenciana (PROMETEO2018/024) for their support. I.O. thanks to Erasmus Mundus Programme, Action 2, Lot 1, Syria, for his predoctoral fellowship. S.S. is grateful to Spanish Ministerio de Economia y Competitividad for his Juan de la Cierva contract (FJCI-2015-27201).

[EN] A simple colorimetric probe for the selective and sensitive detection of neurotransmitter norepinephrine (NE), an important biomarker in the detection of tumors such as pheochromocytoma and paraganglioma, is described. The sensing strategy is based on the use of spherical gold nanoparticles functionalized with benzaldehyde and boronic acid-terminated moieties. A double molecular recognition involving on one hand the aromatic aldehyde and the aminoalcohol group of NE, and on the other hand the boronic acid and the catechol moiety of the neurotransmitter, results in analyte triggered aggregation of the gold nanoparticles, leading to a bathochromic shift of the SPR band in the UV-vis spectrum of the probe and a clear change in the color of the solution from red to blue. Probe P1 shows a remarkable selectivity toward NE versus other catecholamine neurotransmitters (dopamine and epinephrine) and selected biomolecules (S-HIAA, L-Tyr, glucose, uric acid, Lys and glutamic acid). Moreover, a linear response to NE in the 0-1 mu M concentration range was observed and a limit of detection of 0.07 mu M in aqueous media was determined by UV-vis spectroscopy. The sensitivity of the probe toward NE in synthetic urine was also evaluated. In this medium, a limit of detection of 0.09 mu M was obtained which falls within the range of clinical interest, Financial support from the Spanish Government (Projects MAT2015-64139-C4-1-R and MAT2015-64139-C4-4-R) and the Generalitat Valencia (Projects PROMETEOII/2014/047 and AICO/2017/093) is gratefully acknowledged. T. Godoy-Reyes is grateful to the Generalitat Valenciana for her Santiago Grisolia fellowship.

[EN] Microalgae play a fundamental role in aquatic primary production and the food chain. They are a recognized source of fatty acids and fatty acid-based lipids of potential interest in the preparation of functional health products, biofuels and renewable chemicals. The exploitation of this bioresource requires a fine monitoring of each production stage. The aim of this work is the microalgae degradation follow up after the concentration stage at the end of the production process by voltammetric electronic tongue, impedance spectroscopy and H-1 NMR spectroscopy. Microalgae samples were allowed to progress along time (from 1 to 23 days). At scheduled selected times, voltammetry, impedance spectroscopy and H-1 NMR measurements were performed. Multivariate analysis was carried out on these data by PLSR. A model calculated in a training set was then applied to a set of validation to predict the time of evolution. For the three techniques good results in prediction for the validation set were obtained (R-2/RMSEP of 0.961/1.51, 0.956/1.67 and 0.969/1.25 respectively for impedance, voltammetry and NMR spectroscopy). The three techniques were sensitive to the evolution of the microalgae samples. The detection of metabolical changes in the H-1 NMR spectra is also included. This proof of concept could be the basis for future development of rapid and robust strategies for quality control on microalgae production plants., Authors gratefully acknowledge the financial support of MAT2015-64139-C4-1-R and MAT2015-64139-C4-3-R (MINECO/FEDER, UE) and PROMETEOII/2014/047 projects. BUGGYPOWER, S.L. is acknowledged for the financial support and for providing the samples. U26 Nanbiosis is acknowledged by the NMR measurements.

[EN] Here we report the toxicological evaluation of mesoporous silica particles (MSPs) in the nematode C. elegans. Specifically, we have investigated the effect of bare micro- (M0) and nano-sized (N0) MSPs, and their corresponding functionalized particles with a starch derivative (Glu-N) (M1 and N1, respectively) on C. elegans ageing parameters. The toxicity of MSPs, their impact on C. elegans lifespan, movement capacity, progeny and ability to survive upon exposure to acute oxidative stress were assessed. This study demonstrated that both size particles assayed (M0 and N0), labeled with rhodamine and monitored through fluorescence microscopy, are ingested by the nematode. Moreover, toxicity assays indicated that bare nano-sized particles (N0) have a negative impact on the C. elegans lifespan, reducing mobility and progeny production. By contrast, micro-sized particles (M0) proved innocuous for the nematodes. Furthermore, functionalization of nanoparticles with starch derivative reduced their toxicity in C. elegans. Thus, oral intake of N1 comparatively increased the mean lifespan and activity rates as well as resistance to oxidative stress. The overall findings presented here demonstrate the influence of MSP size and surface on their potential toxicity in vivo and indicate the silica-based mesoporous particles to be a potential support for encapsulation in oral delivery applications. Furthermore, the good correlation obtained between healthy aging variables and viability (mean lifespan) validates the use of C. elegans as a multicellular organism for nanotoxicology studies of MSPs., The authors wish to express their gratitude to the Spanish Government (MINECO Projects AGL2012-39597-C02-01, AGL2012-39597-C02-02, AGL2015-70235-C2-1, MAT2012-38429-C04-01 and MAT2015-64139-C4-1), the Generalitat Valenciana (Project PROMETEOII/2014/047) and Colombian Administrative Department of Science, Technology and Research which supported Ms. Acosta Scholarship. We would also like to thank the Institut de Ciencia dels Materials (ICMUV), the Microscopy Service of the Universitat Politecnica de Valencia and the microscopy service of IATA for technical support. We thank Roquette for the Glucidex samples.

[EN] Cellular senescence is a state of stable cell cycle arrest that can negatively affect the regenerative capacities of tissues and can contribute to inflammation and the progression of various aging-related diseases. Advances in the in vivo detection of cellular senescence are still crucial to monitor the action of senolytic drugs and to assess the early onset or accumulation of senescent cells. Here, we describe a naphthalimide-styrene-based probe (HeckGal) for the detection of cellular senescence both in vitro and in vivo. HeckGal is hydrolyzed by the increased lysosomal beta-galactosidase activity of senescent cells, resulting in fluorescence emission. The probe was validated in vitro using normal human fibroblasts and various cancer cell lines undergoing senescence induced by different stress stimuli. Remarkably, HeckGal was also validated in vivo in an orthotopic breast cancer mouse model treated with senescence-inducing chemotherapy and in a renal fibrosis mouse model. In all cases, HeckGal allowed the unambiguous detection of senescence in vitro as well as in tissues and tumors in vivo. This work is expected to provide a potential technology for senescence detection in aged or damaged tissues., R.M. laboratory members thank the financial support from the Spanish Government (project RTI2018-100910-B-C41) and the Generalitat Valenciana (project PROMETEO 2018/024). B.L.-T. is grateful to the Spanish Ministry of Economy for their PhD grants (FPU15/02707). I.G. thanks her contract from IDM. J.F.-B. thanks to his postdoctoral fellowship (CD19/00038). J.A.L.-D. thanks the financial support from the Ministry of Science/MICINN (IJCI-2017-33047). Work in the laboratory of M.S. was funded by the IRB and by grants from the Spanish Ministry of Economy cofunded by the European Regional Development Fund (ERDF) (SAF201348256-R), the European Research Council (ERC-2014-AdG/669622), and the "laCaixa" Foundation. The D.M.-E. laboratory is supported by the Cancer Research U.K. (CRUK), Cambridge Centre Early Detection Programme, by a CRUK Early Detection OHSU project award (C62187/A26989), by a Medical Research Council (MRC) New Investigators Research Grant (NIRG, MR/R000530/1).

[EN] A nanodevice consisted on nanoporous anodic alumina (NAA) supports functionalized with specific and selective antibody-based gatekeepers for the detection of IDH1-R132H mutant enzyme is here reported. Molecular profile and tissue mutations of the tumours (such as IDH1/IDH2 mutations in gliomas) are a great source of information that already make a difference in terms of prognosis and prediction of response to combined therapy. However, standardized methodologies to determine this mutation are time-consuming and cannot provide information before or during surgical intervention, which significantly limits their utility in terms of intraoperative decisionmaking. To solve this limitation, our sensing system, in the presence of the target IDH1-R132H mutant enzyme triggers the delivery of a fluorescent reporter from the antibody-capped NAA that is easily detected using a standard fluorimeter in less than 1 h. Good capabilities of the sensor in terms of sensitivity (limit of detection as low as 0.01 ng/mL) and selectivity are determined. The biosensor is validated in seventeen human glioma tissue samples, also analysed by standardized methodologies, showing significant differences between IDH1 wild-type and IDH1-R132H mutant gliomas (p < 0.01) with high sensitivity, specificity and accuracy (87.5/88.9/88.2) for IDH1-R132H mutational status classification in human glioma tissues. This new detection system might play an important role in surgical interventions, anticipating mutational status information in gliomas and supporting thus decision making and patient survival., This study was supported by the Spanish Government (project RTI2018-100910-B-C41 MCUI/AEI/FEDER, UE), the Generalitat Valenciana (project PROMETEO/2018/024), the Universitat Politecnica de Valencia-Instituto de Investigacion Sanitaria La Fe (GLIOVIEW-IDH and GLIOVIEWIDH_2.0 project) and CIBER-BBN (NANOPATH AND CANDI-EYE projects). S.S. thanks the Instituto de Salud Carlos III and the European Social Fund for the financial support "Sara Borrell" (CD16/000237). L.P. thanks to Ministerio de Economia, Industria y Competitividad for his FPI grant. We also a knowledge service provided by Biobanco La Fe of Instituto de Investigacion Sanitaria La Fe, Val`encia, Spain.

[EN] We report herein an evaluation of the effect of several mesoporous silica nanoparticles (MSNs) on the cellular uptake and in vitro cytotoxicity in human cells. Bare MSNs and MSNs functionalized with polyethylene glycol or hyaluronic acid are employed to evaluate uptake efficiency and mechanisms of endocytosis in cancer (MDA-MB-231) and non-cancer (MCF10A) cells. Moreover, changes in viability, cell cycle, oxidative stress, and mitochondrial membrane potential are evaluated. Our results confirm that MSNs are internalized efficiently by human cells and that uptake mechanisms differ for cell types and particles. We also confirm that MSNs are biocompatible materials that do not induce ROS/RNS production, nor changes on mitochondrial membrane potential or cell cycle., The authors want to thank the Spanish Government RTI2018-100910-B-C41 (MCUI/AEI/FEDER, UE) and PI18/01219 (ISCIII), the Generalitat Valenciana (PROMETEO/2018/024 and ACIF/2016/030), and CIBER-BBN (CB07/01/2012) and CIBER-ONC (CB16/12/00481) for support.

Mesoporous silica microparticles functionalized with lactose for the specific release of essential oil components (EOCs) in the small intestine are presented. In vitro and in vivo intestinal models were applied to validate the microparticles (M41-EOC-L), in which the presence of lactase acts as the triggering stimulus for the controlled release of EOCs. Among the different microdevices prepared (containing thymol, eugenol and cinnamaldehyde), the one loaded with cinnamaldehyde showed the most significant Caco-2 cell viability reduction. On the other hand, interaction of the particles with enterocyte-like monolayers showed a reduction of EOCs permeability when protected into the designed microdevices. Then, a microdevice loaded with cinnamaldehyde was applied in the in vivo model of Wistar rat. The results showed a reduction in cinnamaldehyde plasma levels and an increase in its concentration in the lumen of the gastrointestinal tract (GIT). The absence of payload release in the stomach, the progressive release throughout the intestine and the prolonged stay of the payload in the GIT-lumen increased the bioavailability of the encapsulated compound at the site of the desired action. These innovative results, based on the specific intestinal controlled delivery, suggest that the M41-payload-L could be a potential hybrid microdevice for the protection and administration of bioactive molecules in the small intestine and colon., Ministerio de Ciencia, Innovación y Universidades (Spanish Government) )the Agencia Estatal de Investigación (AEI) and European Union (projects RTI2018-100910-B-C41 and RTI2018-101599-B-C22-AR (MCIU/AEI/ FEDER, EU)), Ministerio de Universidades (Spanish Government) (BG20/00020, A.B. Beatriz Galindo contract), Agencia Estatal de Investigación and European Union through FEDER (Fondo Europeo de Desarrollo Regional, AEI/FEDER EU, project SAF2016-78756), Conselleria de Innovación, Universidades, Ciencia y Sociedad Digital, Generalitat Valenciana (project PROMETEO 2018/024 and E.P-R. predoctoral grant ACIF/2016/023)

[EN] Benzene is a highly toxic aromatic hydrocarbon. Inhaling benzene can cause dizziness, vertigo, headaches, aplasia, mutations and, in the most extreme cases, cancer. Trans,trans-muconic acid (t,t-MA) is one of the metabolization products of benzene. Although different analytical methods have been reported for the determination of t,t-MA, these are often expensive, require trained personnel, are not suitable for on-site measurements, and use hazardous organic solvents. For these reasons, the development of reliable, selective and sensitive methods for rapid and in situ detection of t,t-MA are of importance. Addressing this challenge, a nanodevice for the selective and sensitive quantification of t,t-MA in urine is reported. The nanodevice used is achieved using mesoporous silica nanoparticles loaded with a dye reporter and capped with a dicopper(II) azacryptand. Pore opening and payload release is induced rapidly (10 min) and selectively with t,t-MA in urine, using a simple fluorimeter without sample pretreatment., The authors thank the Spanish Government (RTI2018-100910-B-C41) and the Generalitat Valenciana (PROMETEO 2018/024) for support.

[EN] A bio-inspired nanodevice for the selective and sensitive fluorogenic detection of 3,4- methylenedioxypyrovalerone (MDPV), usually known as Cannibal drug, is reported. The sensing nanodevice is based on mesoporous silica nanoparticles (MSNs), loaded with a fluorescent reporter (rhodamine B) and functionalized on their external surface with a dopamine derivative (3), which specifically interacts with the recombinant human dopamine transporter (DAT), capping the pores. In the presence of MDPV, DAT detaches from the MSNs consequently causing rhodamine B release and allowing drug detection. The nanosensor shows a detection limit of 5.2 µM and it is able to detect the MDPV drug both in saliva and blood plasma samples., The authors thank the Spanish Government (projects RTI2018-100910-B-C41 (MCUI/AEI/FEDER, UE) and CTQ2017-87954-P) and the Generalitat Valencia (PROMETEO/2018/024) for support. E.G. is grateful to the Spanish MEC for her FPU grant. M.A. thanks her postdoctoral fellowship (PAID -10-17). The authors also thank the Electron Microscopy Service at the UPV for support.

[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.

[EN] Oncolytic adenoviruses are a therapeutic alternative to treat cancer based on their ability to replicate selectively in tumor cells. However, their use is limited mainly by the neutralizing antibody (Nab) immune response that prevents repeated dosing. An alternative to facilitate the DNA access to the tumor even in the presence of anti-viral Nabs could be gold nanoparticles able to transfer DNA molecules. However, the ability of these nanoparticles to carry large DNA molecules, such as an oncolytic adenovirus genome, has not been studied. In this work, gold nanoparticles were functionalized with different amounts of polyethylenimine to transfer in a safe and efficient manner a large oncolytic virus genome. Their transfer efficacy and final effect of the oncolytic virus in cancer cells are studied. For each synthesized nanoparticle, (a) DNA loading capacity, (b) complex size, (c) DNA protection ability, (d) transfection efficacy and (e) cytotoxic effect were studied. We observed that small gold nanoparticles (70-80 nm in diameter) protected DNA against nucleases and were able to transfect the ICOVIR-15 oncolytic virus genome encoded in pLR1 plasmid. In the present work, efficient transgene RNA expression, luciferase activity and viral cytopathic effect on cancer cells are reported. These results suggest gold nanoparticles to be an efficient and safe vector for oncolytic adenovirus genome transfer., This research was supported by University of Valencia 'Ayuda a la Investigacion', Asociacion Pablo Ugarte and European Regional Development Fund (VLC-CAMPUS).

Polyphenol oxidase (PPO), also known as tyrosinase and catechol oxidase, is the enzyme responsible for enzymatic browning in foods. It causes undesirable organoleptic, nutritional and colour changes. Here, we report the preparation of five nanomaterials and a study of their ability to modulate PPO enzyme activity. The materials consist of UVM-7 supports (a mesoporous silica material) modified with diverse functional groups (i.e. amine, carboxylic acid, isocyanate, alkane and pyridine). We also studied the PPO immobilisation capability of the materials. All the materials, except the carboxylic acid functionalised one, offer high PPO loading capabilities and the immobilisation speed increases with functionalisation. Nevertheless, only a minor effect of the inhibition of enzymatic browning was produced. Furthermore, the amine containing material was able to capture not only PPO, but also the oxidation products. Such behaviour was validated with fresh apple juice in which browning was avoided, even 90 min in the presence of oxygen at room temperature.

[EN] Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype. In the last years, navitoclax has emerged as a possible treatment for TNBC. Nevertheless, rapid navitoclax resistance onset has been observed thorough Mcl-1 overexpression. As a strategy to overcome Mcl-1-mediated resistance, herein we present a controlled drug co-delivery system based on mesoporous silica nanoparticles (MSNs) targeted to TNBC cells. The nanocarrier is loaded with navitoclax and the Mcl-1 inhibitor S63845 and capped with a MUC1-targeting aptamer (apMUC1-MSNs(Nav/S63845)). The apMUC1-capped nanoparticles effectively target TNBC cell lines and successfully induce apoptosis, overcoming navitoclax resistance. Moreover, navitoclax encapsulation protects platelets against apoptosis. These results point apMUC1-gated MSNs as suitable BH3 mimetics nanocarriers in the targeted treatment of MUC1-expressing TNBC., Gema Vivo-Llorca thanks the Generalitat Valenciana for her fellowship ACIF/2017/072. Vicente Candela-Noguera thanks the Spanish Government for his fellowship FPU15/02753. We would like to thank Servier for the workart used in the figures of this manuscript (Servier Medical Art ). We thank the Spanish Government (project RTI2018-100910-B-C41 (MCUI/AEI/FEDER, UE); SAF2017-84689-R-B (MCUI/AEI/FEDER, UE)) and the Generalitat Valenciana (project PROMETEO/2018/024 and PROMETEO/2019/065) for support.

[EN] Osteoporosis is an illness which appears when the osteoblast/osteoclast activities are unbalanced taking place bone resorption (caused by osteoclasts) in higher extension than bone formation (induced by osteoblasts). Alendronate is one of the most used drugs for osteoporosis treatment despite its scarce bioavailability. Here we present the synthesis and characterization of mesoporous gated nanoparticles (two sets) for the controlled release of alendronate. The first set of nanoparticles (S1) were loaded with sulforhodamine B and capped with a peptide that could be selectively hydrolyzed by cathepsin K enzyme (overexpressed in osteoclasts). The second set (S2) was functionalized with aminopropyl moieties, loaded with nitrobenzofurazan labelled alendronate and capped with the same peptide. Both nanoparticles were internalized by RAW 264.7 macrophages (which could differentiate in osteoclasts) and were able to release its entrapped cargo in the presence of cathepsin K added in the macrophage lysates. Using S2 nanoparticles 4.2% of the total alendronate amount in contact with the cells is liberated inside them and could produce its therapeutic effect., We thank the Spanish Government (RTI2018-100910-B-C41, RTI2018-100910-B-C42 (MCUI/AEI/FEDER, UE)) and the Generalitat Valenciana (PROMETEU/2018/024) for support. SCSIE (Universitat de Valencia) is gratefully acknowledged for all the equipment employed. NMR was registered at the U26 facility of ICTS "NANBIOSIS" at the Universitat of Valencia.

[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.

The addition of light ceramic particles to bulk technological materials as reinforcement to improve their mechanical properties has attracted increasing interest in the last years. The metal matrix composites obtained using nanoparticles have been reported to exhibit an improvement of their properties due to the decrease in the size of the ceramic additives to the nanoscale. Additionally, important effects such as the dispersion of the nanoparticles, wettability, and low reactivity can be controlled by the modification of the nanoparticles&rsquo, surface. In this work, we present the preparation of core&ndash, shell MxOm@SiC nanoparticles with different shell compositions. The accurate and reproducible preparation is developed both at the lab and pilot scale. The synthesis of these core&ndash, shell nanoparticles and their scale-up production are fundamental steps for their industrial use as additives in metal matrix composites and alloys. Powder X-ray diffraction and energy dispersive X-ray (EDX) coupled with scanning transmission electron microscopy (STEM) are used to corroborate the formation of the core&ndash, shell systems, whereas line scan-EDX analysis allows measuring the average shell thickness.

[EN] One appealing concept in the field of hybrid materials is related to the design of gated materials. These materials are prepared in such a way that the release of chemical or biochemical species from voids of porous supports to a solution is triggered upon the application of external stimuli. Such gated materials are mainly composed of two subunits: i) a porous inorganic scaffold in which a cargo is stored, and ii) certain molecular or supramolecular entities, grafted onto the external surface, that can control mass transport from the interior of the pores. On the basis of this concept, a large number of examples are developed in the past ten years. A comprehensive overview of gated materials used in drug delivery applications in in vivo models from 2016 to date is thus given here., The authors thank Spanish Government (Project No. RTI2018-100910-B-C41 (MCUI/AEI/FEDER, UE)) and Generalitat Valenciana (PROMETEO2018/024) for their support.

[EN] A novel nanomachine for dual and sequential delivery of two different compounds was developed by grafting a thiol group and a pH sensitive beta-cyclodextrin-based gate-like ensemble on acetylcholinesterase-modified Au-mesoporous silica Janus nanoparticles., This work was supported by CTQ2017-87954-P and RTI2018100910-B-C41 grants from the Spanish Ministry of Economy and Competitiveness and PROMETEO2018/024 from the Generalitat Valenciana.

[EN] This work reports the synthesis, characterization, and sensing behavior of a hybrid nanodevice for the detection of the potent abuse drug 25I-NBOMe. The system is based on mesoporous silica nanoparticles, loaded with a fluorescent dye, functionalized with a serotonin derivative and capped with the 5-HT2A receptor antibody. In the presence of 25I-NBOMe the capping antibody is displaced, leading to pore opening and rhodamine B release. This delivery was ascribed to 5-HT2A receptor antibody detachment from the surface due to its stronger coordination with 25I-NBOMe present in the solution. The prepared nanodevice allowed the sensitive (limit of detection of 0.6 mm) and selective recognition of the 25I-NBOMe drug (cocaine, heroin, mescaline, lysergic acid diethylamide, MDMA, and morphine were unable to induce pore opening and rhodamine B release). This nanodevice acts as a highly sensitive and selective fluorometric probe for the 25I-NBOMe illicit drug in artificial saliva and in sweets., The authors thank the Spanish Government (projects RTI2018-100910-B-C41 (MCUI/AEI/FEDER, UE) and CTQ2017-87954-P) and the Generalitat Valencia (PROMETEO/2018/024) for support. E.G. is grateful to the Spanish MEC for her FPU grant. The authors also thank the Electron Microscopy Service at the UPV for support.

[EN] Pharmacologically active compounds with preferential cytotoxic activity for senescent cells, known as senolytics, can ameliorate or even revert pathological manifestations of senescence in numerous preclinical mouse disease models, including cancer models. However, translation of senolytic therapies to human disease is hampered by their suboptimal specificity for senescent cells and important toxicities that narrow their therapeutic windows. We have previously shown that the high levels of senescence-associated lysosomal beta-galactosidase (SA-beta-gal) found within senescent cells can be exploited to specifically release tracers and cytotoxic cargoes from galactose-encapsulated nanoparticles within these cells. Here, we show that galacto-conjugation of the BCL-2 family inhibitor Navitoclax results in a potent senolytic prodrug (Nav-Gal), that can be preferentially activated by SA-beta-gal activity in a wide range of cell types. Nav-Gal selectively induces senescent cell apoptosis and has a higher senolytic index than Navitoclax (through reduced activation in nonsenescent cells). Nav-Gal enhances the cytotoxicity of standard senescence-inducing chemotherapy (cisplatin) in human A549 lung cancer cells. Concomitant treatment with cisplatin and Nav-Gal in vivo results in the eradication of senescent lung cancer cells and significantly reduces tumour growth. Importantly, galacto-conjugation reduces Navitoclax-induced platelet apoptosis in human and murine blood samples treated ex vivo, and thrombocytopenia at therapeutically effective concentrations in murine lung cancer models. Taken together, we provide a potentially versatile strategy for generating effective senolytic prodrugs with reduced toxicities., Royal Society, Grant/Award Number: RG160806; Medical Research Council, Grant/Award Number: MR/R000530/1; Cancer Research UK, Grant/Award Number: C62187/A26989 and C62187/A29760; CRUK Cambridge Centre Early Detection Programme, Grant/Award Number: RG86786

[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).

[EN] Candida auris has arisen as an important multidrug-resistant fungus because of several nosocomial outbreaks and elevated rates of mortality. Accurate and rapid diagnosis of C. auris is highly desired; nevertheless, current methods often present severe limitations and produce misidentification. Herein a sensitive, selective, and time-competitive biosensor based on oligonucleotide-gated nanomaterials for effective detection of C. auris is presented. In the proposed design, a nanoporous anodic alumina scaffold is filled with the fluorescent indicator rhodamine B and the pores blocked with different oligonucleotides capable of specifically recognize C. auris genomic DNA. Gate opening modulation and cargo delivery is controlled by successful DNA recognition. C. auris is detected at a concentration as low as 6 CFU/mL allowing obtaining a diagnostic result in clinical samples in one hour with no prior DNA extraction or amplification steps., The authors want to thank the Spanish Government (project RTI2018-100910-B-C41 (MCIU/AEI/FEDER, UE)), the Generalitat Valenciana (project PROMETEO/2018/024), Universitat Politecnica de Valencia-Instituto de Investigacion Sanitaria La Fe (AURISGATE project) and Centro de Investigacion Biomedica en Red en Bioingenieria, Biomateriales y Nanomedicina (NANOPATH AND CANDI-EYE projects) for support. L.P thanks MINECO for his predoctoral fellowship. S.S. thanks the Instituto de Salud Carlos III and the European Social Fund for the financial support "Sara Borrell" (CD16/000237).

[EN] The development of new detection systems for an accurate and rapid identification of pathogens has become an essential challenge in the biomedical field. Herein a highly selective platform based on aptamer-gated nano materials for specific Staphylococcus aureus detection is presented. In the proposed design, a nanoporous anodic alumina (NAA) scaffold is loaded with the fluorescent indicator rhodamine B, while pores entrances are capped by a DNA aptamer which selectively recognizes S. aureus cells in less than 1 h. When S. aureus cells are present, the solid is selectively uncapped, and the dye is released to the medium. This nanodevice allows the detection of bacterial concentrations between 2 and 5 CFU mL-1 (in buffer and blood, respectively) and it has demonstrated excellent behavior in terms of specificity and robustness. A set of 25 different clinical samples are analyzed using this simple procedure obtaining excellent results, which agree with conventional hospital reference techniques for the identification of S. aureus. This new method is sensitive, rapid and low cost, and avoids steps such as polymerase chain amplification reaction, which makes it suitable for use in point-of-care detection systems., This study was supported by the Spanish Government (projects RTI2018-100910-B-C41 and SAF2017-82251-R (MCUI/AEI/FEDER, UE)), the Generalitat Valenciana (project PROMETEO/2018/024), the Universitat Politecnica de Valencia-Instituto de Investigacion Sanitaria La Fe (B02-MIRSA project) and CIBER-BBN (NANOPATH and valorization project CANDI-EYE). It has been also co-financed by the EU through the Valencian Community ERDF PO 2014-2020. S.S. thanks the Instituto de Salud Carlos III and the European Social Fund for the financial support "Sara Borrell" (CD16/000237). L.P. thanks to Ministerio de Economia, Industria y Competitividad for his FPI grant. The authors are grateful for the professional English language editing to Mr. Arash Javadinejad, English Instructor and pubication Editor at the Instituto de Investigacion Sanitaria La Fe, Valencia, Spain.

[EN] A biocomputing strategy implemented in hybrid nanocarriers for controlled cargo delivery is described. The nanodevice consists of enzyme-functionalized Janus Au-mesoporous silica nanoparticles, which behave as an electronic demultiplexer (DEMUX). The nanocarrier is capable of reading molecular information from the environment (lactose) and selecting one of two possible outputs (galactose production or 4-methylumbellilferone release and activation) depending on the presence of an addressing input NAD(+)., The authors wish to thank the Spanish Government (projects RTI2018-100910-B-C41 (MCUI/AEI/FEDER, UE), CTQ2017-87954-P), the Generalitat Valenciana (PROMETEO 2018/024), the Comunidad de Madrid (IND2017/BMD-7642) and CIBER-BBN (NANOCOMMUNITY project) for support.

[EN] Herein, a novel drug photorelease system based on gold nanostars (AuNSts), coated with a mesoporous silica shell and capped with paraffin as thermosensitive molecular gate, is reported. Direct measurements of the surface temperature of a single gold nanostar irradiated using a tightly focused laser beam are performed via a heat sensitive biological matrix. The surface temperature of a AuNSt increases by hundreds of degrees (degrees C) even at low laser powers. AuNSts coated with a mesoporous silica shell using a surfactant-templated synthesis are used as chemotherapeutic nanocarriers. Synthetic parameters are optimized to d avoid AuNSt reshaping, and thus to obtain nanoparticles with suitable and stable plasmonic properties for near-infrared (NIR) laser-triggered cargo delivery. The mesoporous silica-coated nanostars are loaded with doxorubicin (Dox) and coated with octadecyltrimethoxysilane and the paraffin heneicosane. The paraffin molecules formed a hydrophobic layer that blocks the pores, impeding the release of the cargo. This hybrid nanosystem exhibits a well-defined photodelivery profile using NIR radiation, even at low power density, whereas the nonirradiated sample shows a negligible payload release. Dox-loaded nanoparticles displayed no cytotoxicity toward HeLa cells, until they are irradiated with 808 nm laser, provoking paraffin melting and drug release. Hence, these novel, functional, and biocompatible nanoparticles display adequate plasmonic properties for NIR-triggered drug photorelease applications., The authors gratefully acknowledge financial support from the Spanish Government (Projects AGL2015-70235-C2-2-R and MAT2015-64139-C4-1-R), the Generalitat Valenciana (Project PROMETEOII/2014/047), and European Union (Programme European Union Action 2 Erasmus Mundus Partnerships, Grant-2014-0870/001-001). A. Samadi and L. B. Oddershede acknowledge financial support from the Novo Nordisk Foundation (NNF14OC0011361) and from the Danish National Research Foundation (DNRF116). A. H. Montoto thanks Erasmus Mundus Programme for his PhD scholarship at EurolnkaNet project. The authors thank UPV electron microscopy and CIPF confocal and electron microscopy services for technical support.

[EN] Colon targeted drug delivery is highly relevant not only to treat colonic local diseases but also for systemic therapies. Mesoporous silica nanoparticles (MSNs) have been demonstrated as useful systems for controlled drug release given their biocompatibility and the possibility of designing gated systems able to release cargo only upon the presence of certain stimuli. We report herein the preparation of three gated MSNs able to deliver their cargo triggered by different stimuli (redox ambient (S1), enzymatic hydrolysis (S2), and a surfactant or being in contact with cell membrane (S3)) and their performance in solution and in vitro with Caco-2 cells. Safranin O dye was used as a model drug to track cargo fate. Studies of cargo permeability in Caco-2 monolayers demonstrated that intracellular safranin O levels were significantly higher in Caco-2 monolayers when using MSNs compared to those of free dye. Internalization assays indicated that S2 nanoparticles were taken up by cells via endocytosis. S2 nanoparticles were selected for in vivo tests in rats. For in vivo assays, capsules were filled with S2 nanoparticles and coated with Eudragit FS 30 D to target colon. The enteric coated capsule containing the MSNs was able to deliver S2 nanoparticles in colon tissue (first step), and then nanoparticles were able to deliver safranin O inside the colonic cells after the enzymatic stimuli (second step). This resulted in high levels of safranin O in colonic tissue combined with low dye levels in plasma and body tissues. The results suggested that this combination of enzyme-responsive gated MSNs and enteric coated capsules may improve the absorption of drugs in colon to treat local diseases with a reduction of systemic effects., The authors acknowledge the financial support from the Spanish Government (Projects MAT2015-64139-C4-1-R, SAF2016-78756 and AGL2015-70235-C2-2-R) and the Generalitat Valenciana (Project GVA/2014/13).

[EN] Essential oils and their main compounds have been studied in-depth for their antifungal properties against a wide variety of microorganisms. However, the strong odour emitted by them, even at low concentrations, makes their incorporation into food matrices difficult. Immobilisation of antimicrobial compounds on solid surfaces could be a strategy to reduce their odour impact. The antifungal effectiveness of eugenol and thymol bioactive agents, free and immobilised on mesoporous silica microparticles (MCM-41 family), and their impact on the final aroma and fungal decay of strawberry jam, were evaluated herein. Free eugenol and thymol exhibited good antifungal properties against the fungi strains tested, and thymol proved more effective. The antifungal activity of immobilised eugenol and thymol displayed greater antifungal activity for immobilised eugenol. The jams prepared with immobilised eugenol on MCM-41 microparticles exhibited no mould and yeast development during the studied storage time. The sensory evaluation confirmed that eugenol and thymol immobilisation reduced their typical strong impact on strawberry jam flavour. This work demonstrates the promising use of immobilised eugenol on mesoporous silica microparticles to control strawberry jam decay. (C) 2017 Elsevier Ltd. All rights reserved., Authors gratefully acknowledge the financial support from MINECO-Spanish Government and FEDER-EU (Projects AGL2012-39597-C02-01, AGL2015-70235-C2-1-R and MAT2015-64139-C4-1) and the Generalitat Valencia (Project PROMETEOII/2014/047). Furthermore, author Susana Ribes is grateful to the Universitat Politecnica de Valencia (UPV) for her FPI grant.

[EN] Mesoporous silica nanoparticles loaded with rhodamine B and capped with a bisphenol A aptamer were used for the selective and sensitive detection of this lethal chemical. The pores of the nanoparticles are selectively opened in the presence of bisphenol A (through its selective coordination with the aptamer) with subsequent rhodamine B delivery. With this capped material a limit of detection as low as 3.5 mu m of bisphenol A was measured., We 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) for support. A.R. thanks UPV for her predoctoral fellowship. A.B. thanks the Spanish Government for the finantial support "Juan de la Cierva-Incorporacion" (IJCI-2014-21534). The authors also thank the Electron Microscopy Service at the UPV for support.

[EN] Folic acid (FA) is a synthetic vitamin commonly used for food fortification. However, its vulnerability to processing and storage implies loss of efficiency, which would induce over-fortification by processors to obtain a minimum dose upon consumption. Recent studies have indicated potential adverse effects of FA overdoses, and FA protection during processing and storage could lead to more accurate fortification. In addition, sustained vitamin release after consumption would help improve its metabolism. The objective of this work was to study controlled FA delivery and stability in fruit juices to reduce potential over-fortification risks by using gated mesoporous silica particles (MSPs). The obtained results indicated that FA encapsulation in MSPs significantly improved its stability and contributed to controlled release after consumption by modifying vitamin bioaccessibility. These results confirmed the suitability of MSPs as support for controlled release and protection of bioactive molecules in food matrices in different food production and storage stages., Authors gratefully acknowledge the financial support from the Ministerio de Economia y Competitividad and FEDER-EU (Projects AGL2012-39597-C02-01, 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 Ciencia e Innovacion for her grant (AP2010-4369). The authors also thank the Electron Microscopy Service at the UPV for support.

[EN] Mesoporous silica nanoparticles loaded with fluorescein and capped by a pseudorotaxane, formed between a naphthalene derivative and cyclobis(paraquat-p-phenylene) (CBPQT(4+)), were used for the selective and sensitive fluorogenic detection of 3,4-methylenedioxy-methamphetamine (MDMA)., The authors acknowledge the financial support from the Spanish Government (projects MAT2015-64139-C4-1-R and AGL2015-70235-C2-2-R) and the Generalitat Valenciana (project GVA/2014/13). B. L-T. is grateful to the Ministerio de Economia y Competitividad for her PhD grant. A. B. thanks the Spanish Government for the financial support "Juan de la CiervaIncorporacion'' (IJCI-2014-21534). J. O. J. thanks The Danish Natural Science Research Council (FNU, project no. 11-106744) and the Villum Foundation for financial support.