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[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.

The increasing cases of bacterial infections originating from resistant bacteria are a serious problem globally and many approaches have been developed for different purposes to treat bacterial infections. Aerogels are a novel class of smart porous materials composed of three-dimensional networks. Recently, aerogels with the advantages of ultra-low density, high porosity, tunable particle and pore sizes, and biocompatibility have been regarded as promising carriers for the design of delivery systems. Recently, aerogels have also been provided with antibacterial activity through loading of antibacterial agents, incorporation of metal/metal oxides and via surface functionalization and coating with various functional groups. In this mini-review, the synthesis of aerogels from both conventional and low-cost precursors is reported and examples of aerogels displaying antibacterial properties are summarized. As a result, it is clear that the encouraging antibacterial performance of aerogels promotes their use in many antibacterial applications, especially in the food industry, pharmaceutics and medicine.

[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.

We report herein a gene-directed enzyme prodrug therapy (GDEPT) system using gated mesoporous silica nanoparticles (MSNs) in an attempt to combine the reduction of side effects characteristic of GDEPT with improved pharmacokinetics promoted by gated MSNs. The system consists of the transfection of cancer cells with a plasmid controlled by the cytomegalovirus promoter, which promotes β-galactosidase (β-gal) expression from the bacterial gene lacZ (CMV-lacZ). Moreover, dendrimer-like mesoporous silica nanoparticles (DMSNs) are loaded with the prodrug doxorubicin modified with a galactose unit through a self-immolative group (DOXO-Gal) and modified with a disulfide-containing polyethyleneglycol gatekeeper. Once in tumor cells, the reducing environment induces disulfide bond rupture in the gatekeeper with the subsequent DOXO-Gal delivery, which is enzymatically converted by β-gal into the cytotoxic doxorubicin drug, causing cell death. The combined treatment of the pair enzyme/DMSNs-prodrug are more effective in killing cells than the free prodrug DOXO-Gal alone in cells transfected with β-gal.

[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).

In nature, coordinated communication between different entities enables a group to accomplish sophisticated functionalities that go beyond those carried out by individual agents. The possibility of programming and developing coordinated communication networks at the nanoscale—based on the exchange of chemical messengers—may open new approaches in biomedical and communication areas. Here, a stimulus-responsive circular model of communication between three nanodevices based on enzyme-functionalized Janus Au–mesoporous silica capped nanoparticles is presented. The output in the community of nanoparticles is only observed after a hierarchically programmed flow of chemical information between the members., A community of three nanodevices communicates through a hierarchically programmed circular flow of chemical information between members.

Many important human diseases, and especially cancer, have been related to the overproduction of 8-oxo-7,8-dihydro-2 '-deoxyguanosine (8-oxo-dG). This molecule is a product of oxidative stress processes over nucleophilic bases in DNA. In this work, an aptasensor for the rapid, selective and accurate detection of this oncomarker is presented. The aptasensor consists of a nanoporous anodic alumina material loaded with a dye and is functionalized with an aptamer-based "molecular gate". In the presence of target 8-oxo-dG, the capping aptamer displaces from the surface due to the high affinity of the analyte with the capping aptamer, thus inducing delivery of the preloaded fluorescent dye. In contrast, in the absence of 8-oxo-dG, a poor payload delivery is accomplished. This aptamer-based nanodevice has great sensitivity for 8-oxo-dG, resulting in a LOD of 1 nM and a detection time of ca. 60 min. Moreover, the aptasensor is able to accurately detect 8-oxo-dG in unmodified urine and serum without pre-concentration treatments. This diagnostic tool is validated in a set of 38 urine and serum samples from patients diagnosed of colorectal cancer and control patients. These samples are also analyzed using a standardized and specific ELISA kit. The aptasensor displays excellent sensitivity (95.83/100%) and specificity (80/100%) for 8-oxo-dG detection in serum and urine samples, respectively. Our results may serve as a basis for the development of generalized fluorogenic diagnostic platforms for the easy diagnosis of cancer in biofluids as well as for monitoring therapeutic treatments and detection of relapses without the use of expensive equipment or trained personnel.

[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.

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)

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.

[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.

Background The rising incidence of renal cell carcinomas (RCC) constitutes a significant challenge owing to risk of overtreatment. Because aberrant microRNA (miR) promoter methylation contributes to cancer development, we investigated whether altered miR-30a-5p expression associates with DNA promoter methylation and evaluated the usefulness as clear cell RCC (ccRCC) diagnostic and prognostic markers. Methods Genome-wide methylome and RNA sequencing data from a set of ccRCC and normal tissue samples from The Cancer Genome Atlas (TCGA) database were integrated to identify candidate CpG loci involved in cancer onset. MiR-30a-5p expression and promoter methylation were quantitatively assessed by PCR in a tissue set (Cohort #1) and urine sets (Cohorts #2 and 3) from IPOPorto and Homburg University Hospital. Non-parametric tests were used for comparing continuous variables. MiR-30a-5p promoter methylation (miR-30a-5pme) performance as diagnostic (receiver operator characteristics [ROC] - validity estimates) and prognostic [metastasis-free (MFS) and disease-specific survival (DSS)] biomarker was further validated in urine samples from ccRCC patients by Kaplan Meier curves (with log rank) and both univariable and multivariable analysis. Results Two significant hypermethylated CpG loci in TCGA ccRCC samples, correlating with miR-30a-5p transcriptional downregulation, were disclosed. MiR-30a-5pme in ccRCC tissues was confirmed in an independent patient’s cohort of IPOPorto and associated with shorter time to relapse. In urine samples, miR-30a-5pme levels identified cancer both in testing and validation cohorts, with 83% sensitivity/53% specificity and 63% sensitivity/67% specificity, respectively. Moreover, higher miR-30a-5pme levels independently predicted metastatic dissemination and survival. Conclusion To the best of our knowledge, this is the first study validating the diagnostic and prognostic potential of miR-30a-5pme for ccRCC in urine samples, providing new insights for its clinical usefulness as non-invasive cancer biomarker.

[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).

The rising incidence of renal cell carcinomas (RCC) constitutes a significant challenge owing to risk of overtreatment. Because aberrant microRNA (miR) promoter methylation contributes to cancer development, we investigated whether altered miR-30a-5p expression associates with DNA promoter methylation and evaluated the usefulness as clear cell RCC (ccRCC) diagnostic and prognostic markers.Genome-wide methylome and RNA sequencing data from a set of ccRCC and normal tissue samples from The Cancer Genome Atlas (TCGA) database were integrated to identify candidate CpG loci involved in cancer onset. MiR-30a-5p expression and promoter methylation were quantitatively assessed by PCR in a tissue set (Cohort #1) and urine sets (Cohorts #2 and 3) from IPOPorto and Homburg University Hospital. Non-parametric tests were used for comparing continuous variables. MiR-30a-5p promoter methylation (miR-30a-5pTwo significant hypermethylated CpG loci in TCGA ccRCC samples, correlating with miR-30a-5p transcriptional downregulation, were disclosed. MiR-30a-5pTo the best of our knowledge, this is the first study validating the diagnostic and prognostic potential of miR-30a-5p

[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.

Ciprofloxacin, a second generation fluoroquinolone antibiotic, is one of the top pharmaceutical contaminants in water and many approaches have been developed for the removal of ciprofloxacin in wastewater. In this study, ciprofloxacin adsorption is carried out using a low-cost silica xerogel synthesized by a simple sol-gel method. The effect of pH, contact time, initial concentration of ciprofloxacin and temperature on the adsorption of ciprofloxacin by the silica xerogel is investigated. At optimum adsorption conditions, the experimental data fits well to a Langmuir isotherm and a pseudo-second-order kinetic model. The maximum ciprofloxacin adsorption capacity is determined as 24.45 mg g−1. Thermodynamic parameters show that ciprofloxacin adsorption by the silica xerogel is a spontaneous endothermic process. Moreover, reusability experiments reveal that the silica xerogel can be effectively used several times for ciprofloxacin adsorption. The promising results indicate that the silica xerogel can be regarded as potential adsorbent for ciprofloxacin removal.

[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] 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.

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] 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] 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] 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] We describe herein the preparation of glucose-sensitive capped mesoporous silica nanoparticles for insulin delivery. The new material consists of an expanded-pore nanometric silica support grafted with 1-propyl-1-H-benzimidazole groups, loaded with fluorescein isothiocyanate-labeled insulin (FITC-Ins) and capped by the formation of inclusion complexes between cyclodextrin-modified glucose oxidase (CD-GOx) and the benzimidazole groups grafted on the mesoporous support. Insulin delivery from the gated material in simulated blood plasma was assessed upon addition of glucose. Glucose is transformed by GOx into gluconic acid, which promoted the dethreading of the benzimidazole-CD-GOx inclusion complexes, allowing cargo release. Small quantities of this support would be needed to release the amount of insulin necessary to decrease diabetic blood glucose concentrations to regular levels., The authors thank the Spanish Government (projects CTQ2011-24355, MAT2015-64139-C4-1-R, CTQ2014-58989-P, and AGL2015-70235-C2-2-R (MINECO/FEDER)) and the Generalitat Valenciana (project PROMETEOII/2014/047) for support. M.O. thanks the Universitat Politecnica de Valencia for her FPI grant. P.D. thanks the Ministerio de Economia y Competitividad for her FPI grant (BES-2012-054066). C.C. thanks the Generalitat Valenciana for her postdoctoral contract VALi+D.

[EN] Magnetic hyperthermia mediated by superparamagnetic particles is mainly based in sinusoidal waveforms as excitation signals. Temperature changes are conventionally explained by rotation of the particles in the surrounding medium. This is a hypothesis quite questionable since habitual experimental setups only produce changes in the magnetic module, not in the field lines trajectories. Theoretical results were tested by changing the waveform of the exciting signal in order to compare non-sinusoidal signals against sinusoidal signals. Experiments were done at different frequencies: 200 KHz, 400 KHz, 600 KHz, 800 KHz and 1 MHz. Super paramagnetic Iron Oxide samples (SPION), made of magnetite (Fe3O4) and suspended in water (100 mg/ml), were used. Magnetic field strength varies from 0.1 +/- 0.015 KA/m to 0.6 +/- 0.015 KA/m. In this study was observed that the power loss depends on the applied frequency: for 1 to 2.5 RMS current the responses for each signal are part of the higher section of the exponential function, and for 3.5 to 8 RMS current the response is clearly the decrement exponential function's tale (under 1 x 10(3) LER/gr).

[EN] Infections represent one of the most frequent causes of arthroplasty revision. Thus, design of new antimi-crobial scaffolds to reduce implant rejections, bone infections and associated medical costs is highlydesired. In recent years, essential oil components (EOCs) have merged as compounds with signi¿cantantimicrobial activity that can be attached to speci¿c surfaces to enhance and prolong their antimicrobialeffect. Herein calcium phosphate CaP regenerative materials have been coated with a vanillin derivativeto combine its original bone regeneration properties with antimicrobial action of EOCs. Materials in formof microparticles and blocks were prepared and fully characterized. Clonogenic viability tests demon-strated that low concentrations of material (10 mg/mL-1) resulted effective to kill 100% of E. coli DH5abacteria. Additionally, vanillin containing scaffolds did not display any toxic effect over cells, yet theypreserve the ability to express alkaline phosphatase (ALPL), collagen type 1, chaina1(COL1A1) and bonegamma-carboxyglutamic acid-containing protein or osteocalcin (BGLAP), which are genes typicallyexpressed by osteoblasts. These results demonstrate that commercially available scaffolds can be func-tionalized with EOCs, achieving antimicrobial activity and open up a new approach for the treatmentand prevention of infection., The authors thank the Spanish Government, Spain for projects MAT2015-64139-C04-01-R (MINECO/FEDER). Also, Generalitat Valenciana, Spain (project PROMETEOII/2014/047) is acknowledged for their support. L. P. thanks Universitat Politecnica de Valencia, Spain for her FPI and mobility grants. B.D. thanks to Ministerio de Economia, Ciencia y Competitividad, Spain for his Juan de la Cierva-Formation fellowship. The authors also thank the Electron Microscopy Service at the UPV for their support. The authors are grateful to IRCCS Rizzoli Orthopaedic Institute, Italy (funds 5 X 1000 year 2015, cod. 6879).

The development of new strategies to detect microRNAs (miRNAS) has become an important challenge in the biomedical field. We report herein the use of oligonucleotide-gated silica nanoparticles for the detection of miRNA-145. In the proposed design, mesoporous silica nanoparticles (MSNs) are loaded with a fluorescent reporter (rhodamine B) and pores are blocked by specific DNA oligonucleotides. The opening of the gated system and dye delivery is selectively controlled by DNA-miRNA recognition. Moreover, the use of DNA capture probes able to form duplex or triplex structures between target miRNA and the complementary oligonucleotides has been studied. By this simple procedure a limit of detection as low as 0.25 pM was found for miRNA. The method was successfully applied to detect miRNA-145 in serum samples, which demonstrates the high potential of these capped materials to detect miRNA for diagnostic purposes., We thank the Spanish Government (projects MAT2015-64139-C4-1-R and CTQ2014-52588-R (MINECO/FEDER)), the Generalitat Valenciana (project PROMETEOII/2014/047) and the Generalitat de Catalunya (2014/SGR/624) for support. A.R. thanks UPV for her predoctoral fellowship. S.S. thanks the Instituto de Salud Carlos III and the European Social Fund for the financial support “Sara Borrell” (CD16/000237). V.C.-N. thanks Ministerio de Educación, Cultura y Deporte for his predoctoral grant. The authors also thank the Electron Microscopy Service at the UPV for support.

The aim of this study was to analyze whether FeNO levels in acute exacerbation of COPD (AECOPD) with hospital admission have better diagnostic value than eosinophilia in blood, and to evaluate its usefulness in predicting a better clinical response. An observational prospective study of patients with AECOPD was carried out. FeNO determinations were made on arrival at the emergency room (ER), at discharge and during stability 3-6 months after discharge. Co-morbidities, bronchodilators, inhaled (IGC) and systemic (SGC) glucocorticoids, eosinophils, systemic inflammation markers (procalcitonin, C-reactive protein), eosinophil cationic protein, and total IgE were collected. Fifty consecutive patients (92% men, mean age 75 ± 6 years) were included in this study. Phenotypes were 26% Asthma-COPD Overlap Syndrome (ACOS), 42% chronic bronchitis (CB) and 32% emphysema. ACOS patients showed significantly higher levels of FeNO (73 ppb) and eosinophils (508 cells/mm3) than the rest (CB: 23 ppb, 184 cells/mm3, emphysema: 27 ppb, 159 cells/mm3; p < 0.05). A significant correlation between FeNO levels measured in ER and eosinophils was observed (r = 0.7; p < 0.001), but not at discharge or in stable phase. No significant association was found with parameters of systemic inflammation and mean stay. In conclusion, the determination of FeNO in AECOPD does not offer advantages over the evaluation of eosinophilia. These parameters rise at arrival in ER, descend at discharge, and remain unchanged in the stable phase. Both present similar diagnostic utility and are able to better identify the ACOS phenotype, which helps select a population that could benefit from a glucocorticoids therapy. Sin financiación 2.503 JCR (2018) Q3, 37/63 Respiratory System 1.034 SJR (2018) Q1, 526/2488 Medicine (miscellaneous) No data IDR 2018 UEM

Core-shell nanoparticles comprised of Fe3O4 cores and a mesoporous silica shell with an average expanded pore size of 6.07 nm and coated with a poly(N-isopropylacrylamide) (PNIPAM) layer (CS MSNs EP PNIPAM) were prepared and characterized. The nanoparticles was loaded with (Ru(bipy)3 2+) dye or an antibacterial enzyme, lysozyme, to obtain CS MSNs EP PNIPAM Ru(bipy)3 2+ and CS MSNs EP PNIPAM Lys, respectively. The lysozyme loading was determined to be 160 mg/g of nanoparticle. It was seen that Ru(bipy)3 2+ and lysozyme release was minimal at a room temperature of 25 ºC while at physiological temperature (37 º C), abrupt release was observed. The applicability of the CS MSNs EP PNIPAM Lys was further tested with two Gram-positive bacteria samples, Bacillus cereus and Micrococcus luteus. At physiological temperature, the nanoparticles were shown to reduce bacterial growth, indicating a successful release of lysozyme from the nanoparticles. This nanoparticle system shows potential as a nanocarrier for the loading of similarly sized proteins or other species as a drug delivery platform., The authors wish to express their gratitude to the facilities at Ciudad Politecnica de la Innovacion (CPI), El Centro de Reconocimiento Molecular y Desarrollo Tecnologico (IDM), the Biotechnology Department at UPV, and the Instituto de Biologia Molecular y Celular de Plantas (IBMCP) at UPV for assistance in the materials characterization techniques and for providing the bacterial samples for antibacterial testing. Warm thanks are given to the Transatlantic Partnership for Excellence in Engineering (TEE) program, an Erasmus Mundus-Action 2 project by the European Commission, for the opportunity to undertake research at the collaborating university, UPV. The University of California Office of the President (UCOP) Lab Fees Research Program funded this research. The authors also thank the Spanish Government (Projects MAT2012-38429-C04-01 and MAT2012-38429-C04-03), the Generalitat Valenciana (Project PROMETEOII/2014/047) for support.

[EN] An increase of bone diseases incidence has boosted the study of ceramic biomaterials as potential osteo-inductive scaffolds. In particular, mesoporous bioactive glasses have demonstrated to possess a broad application in the bone regeneration field, due their osteo-regenerative capability and their ability to release drugs from the mesoporous structure. These special features have been studied as an option to fight against bone infection, which is one of the most common problems regarding bone regeneration therapies. In this work, a mesoporous bioglass functionalized with polyamines and capped with adenosine triphosphate (ATP) as the molecular gate was developed for the controlled release of the antibiotic levofloxacin. Phosphate bonds of ATP were hydrolyzed in the presence of acid phosphatase (APase), the concentration of which is significantly increased in bone infection due to the activation of bone resorption processes. The solid was characterized and tested successfully against bacteria. The final gated solid induced bacterial death only in the presence of acid phosphatase. Additionally, it was demonstrated that the solid is not toxic against human cells. The double function of the prepared material as a drug delivery system and bone regeneration enhancer confirms the possible development of a new approach in the tissue engineering field, in which controlled release of therapeutic agents can be finely tuned and, at the same time, osteoinduction is favored., The authors thank the Spanish Government for projects MAT2015-64139-C04-01-R, MAT2015-64831-R and MAT2016-75611-R (AEI/FEDER, UE). Generalitat Valenciana (project PROMETEOII/2014/047) and CIBER-BBN (project SPRING) are also acknowledged for their support. M.V.R. acknowledges funding from the European Research Council (Advanced Grant VERDI; ERC-2015-AdG Proposal 694160). L.P. thanks Universitat Politecnica de Valencia for her FPI grant. N.G.C. and A.G. thank to Ministerio de Ciencia e Innovacion and Ministerio de Educacion, Cultura y Deporte for their predoctoral fellowships. The authors also thank the Electron Microscopy Service at the UPV for their support.

[EN] Gated mesoporous silica nanoparticles can deliver payload upon the application of a predefined stimulus, and therefore are promising drug delivery systems. Despite their important role, relatively low emphasis has been placed on the design of gating systems that actively target carbohydrate tumor cell membrane receptors. We describe herein a new Lewis X (Le(x)) antigen-targeted delivery system comprising mesoporous silica nanoparticles (MSNs) loaded with ATTO 430LS dye, functionalized with a Le(x) derivative (1) and capped with a fucose-specific carbohydrate-binding protein (Aleuria aurantia lectin (AAL)). This design takes advantage of the affinity of AAL for Le(x) overexpressed receptors in certain cancer cells. In the proximity of the cells, AAL is detached from MSNs to bind Le(x), and selectins in the cells bind Le(x) in the gated MSNs, thereby inducing cargo delivery. Gated MSNs are nontoxic to colon cancer DLD-1 cells, and ATTO 430LS dye delivered correlated with the amount of Le(x) antigen overexpressed at the DLD-1 cell surface. This is one of the few examples of MSNs using biologically relevant glycans for both capping (via interaction with AAL) and targeting (via interaction with overexpressed Le(x) at the cell membrane)., The authors thank the Spanish Government (Projects MAT2015-64139-C4-1-R and MAT2013-46101-R (MINECO/ FEDER)), Fondo de Investigacion Sanitaria (PI15/00480) and Generalitat Valenciana (Project PROMETEOII/2014/047 and project GVA/2014/13) for support. R. B. is thankful to Svagata. Eu (Erasmus Mundus Action-II program) for his fellowship. The authors also thank the Electron Microscopy Service at the UPV for support.

[EN] Mesoporous silica nanoparticles loaded with safranin O and capped with disulfide-containing oligo(ethylene glycol) chains were used for the selective and sensitive fluorimetric detection of glutathione., Financial support from the Spanish Government (Project MAT2012-38429-C04-01) and the Generalitat Valencia (Project PROMETEOII/2014/047) is gratefully acknowledged. S. E. is grateful to the Generalitat Valenciana for his Santiago Grisolia fellow. Also, C. G. is grateful to the Spanish Ministry of Science and Innovation for the grant.