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[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] 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).

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] 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.

[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] 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] 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.

[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] 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] 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] 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.

Cancer is responsible for more than 12% of all causes of death in the world, with an annual death rate of more than 7 million people. In this scenario melanoma is one of the most aggressive ones with serious limitation in early detection and therapy. In this direction we developed, characterized and tested in vivo a new drug delivery system based on magnetic core-mesoporous silica nanoparticle that has been doped with dacarbazine and labelled with technetium 99 m to be used as nano-imaging agent (nanoradiopharmaceutical) for early and differential diagnosis and melanoma by single photon emission computed tomography. The results demonstrated the ability of the magnetic core-mesoporous silica to be efficiently (>98%) doped with dacarbazine and also efficiently labelled with 99mTc (technetium 99 m) (>99%). The in vivo test, using inducted mice with melanoma, demonstrated the EPR effect of the magnetic core-mesoporous silica nanoparticles doped with dacarbazine and labelled with technetium 99 metastable when injected intratumorally and the possibility to be used as systemic injection too. In both cases, magnetic core-mesoporous silica nanoparticles doped with dacarbazine and labelled with technetium 99 metastable showed to be a reliable and efficient nano-imaging agent for melanoma.

[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.

[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.

[EN] Cargo delivery from mesoporous silica nanoparticles loaded with sulforhodamine B and capped with a difluoroboron-dipyrromethene (BODIPY) derivative was triggered by a NO2-induced oxidative process., The authors thank the financial support from the Spanish Government (project MAT2015-64139-C4-R) and the Generalitat Valenciana (project GVA/2014/13).

[EN] Gold nanostars coated with a mesoporous silica shell and functionalized with poly(ethylene glycol) containing photolabile 2-nitrobenzyl moieties are able to release doxorubicin after NIR light irradiation at low power irradiance via a multiphoton absorption photo-dissociation process., The authors gratefully acknowledge financial support from the Spanish Government (projects RTI2018-100910-B-C41 and RTI2018-101599-B-C22 (MCUI/AEI/FEDER,UE)), the Generalitat Valenciana (Project PROMETEO2018/024) and the European Union (Programme European Union Action 2-Erasmus Mundus Partnerships, Grant Agreement Number-2014-0870/001-001). A.H.-M. thanks the Erasmus Mundus Programme for his PhD scholarship for the EuroInkaNet project.

[EN] Bacterial infections are the main cause of chronic infections and even mortality. In fact, due to extensive use of antibiotics and, then, emergence of antibiotic resistance, treatment of such infections by conventional antibiotics has become a major concern worldwide. One of the promising strategies to treat infection diseases is the use of nanomaterials. Among them, mesoporous silica materials (MSMs) have attracted burgeoning attention due to high surface area, tunable pore/particle size, and easy surface functionalization. This review discusses how one can exploit capacities of MSMs to design and fabricate multifunctional/controllable drug delivery systems (DDSs) to combat bacterial infections. At first, the emergency of bacterial and biofilm resistance toward conventional antimicrobials is described and then how nanoparticles exert their toxic effects upon pathogenic cells is discussed. Next, the main aspects of MSMs (e.g., physicochemical properties, multifunctionality, and biosafety) which one should consider in the design of MSM-based DDSs against bacterial infections are introduced. Finally, a comprehensive analysis of all the papers published dealing with the use of MSMs for delivery of antibacterial chemicals (antimicrobial agents functionalized/adsorbed on mesoporous silica (MS), MS-loaded with antimicrobial agents, gated MS-loaded with antimicrobial agents, MS with metal-based nanoparticles, and MS-loaded with metal ions) is provided., The authors thank the Spanish Government (projects MAT2015-64139-C4-1-R and AGL2015-70235-C2-2-R (MINECO/FEDER)) and the Generalitat Valenciana (project PROMETEOII/2014/047 and PROMETEO/2018/024) for support. A.B. thanks the Spanish Government for her Juan de la Cierva incorporacion contract IJCI-2014-21534.

[EN] Janus gold nanostar-mesoporous silica nanoparticle (AuNSt-MSNP) nanodevices able to release an entrapped payload upon irradiation with near infrared (NIR) light were prepared and characterized. The AuNSt surface was functionalized with a thiolated photolabile molecule (5), whereas the mesoporous silica face was loaded with a model drug (doxorubicin) and capped with proton-responsive benzimidazole-beta-cyclodextrin supramolecular gatekeepers (N 1). Upon irradiation with NIR-light, the photolabile compound 5 photodissociated, resulting in the formation of succinic acid, which induced the opening of the gatekeeper and cargo delivery. In the overall mechanism, the gold surface acts as a photochemical transducer capable of transforming the NIR-light input into a chemical messenger (succinic acid) that opens the supramolecular nanovalve. The prepared hybrid nanoparticles were non-cytotoxic to HeLa cells, until they were irradiated with a NIR laser, which led to intracellular doxorubicin release and hyperthermia. This induced a remarkable reduction in HeLa cells viability., The authors gratefully acknowledge financial support from the Spanish Government [Projects MAT2015-64139-C4-1-R, AGL2015-70235-C2-2-R and SAF2017-84689-R (MINECO/AEI/FEDER, UE)], the Generalitat Valenciana (Project PROMETEO2018/024) and European Union (Erasmus Mundus Programme, Action 2, grant agreement number 2014-0870/001001). A.H. thanks the Erasmus Mundus Programme for his PhD scholarship through the EuroInkaNet project. A.L.-L. thanks "La Caixa" Banking Foundation for his PhD scholarship.

[EN] Silica mesoporous microparticles loaded with both rhodamine B fluorophore (S1) or hydrocortisone (S2), and capped with an olsalazine derivative, are prepared and fully characterized. Suspensions of Si and S2 in water at an acidic and a neutral pH show negligible dye/drug release, yet a notable delivery took place when the reducing agent sodium dithionite is added because of hydrolysis of an azo bond in the capping ensemble. Additionally, olsalazine fragmentation induced 5-aminosalicylic acid (5-ASA) release. In vitro digestion models show that S1 and S2 solids are suitable systems to specifically release a pharmaceutical agent in the colon. In vivo pharmacokinetic studies in rats show a preferential rhodamine B release from Si in the colon. Moreover, a model of ulcerative colitis is induced in rats by oral administration of 2,4,6-trinitrobenzenesulfonic acid (TNBS) solutions, which was also used to prove the efficacy of S2 for colitis treatment. The specific delivery of hydrocortisone and 5-ASA from S2 material to the colon tissue in injured rats markedly lowers the colon/body weight ratio and the clinical activity score. Histological studies showed a remarkable reduction in inflammation, as well as an intensive regeneration of the affected tissues., We thank the Generalitat Valenciana (Project PROMETE02018/024) and the Spanish Government (Projects AGL2015-70235-C2-2-R and MAT2015-64139-C4-1-R (MINECO/FEDER)) for support. A.H.T. thanks the Spanish MEC for his FPU fellowship. The authors also thank the support of the Electron Microscopy Service at the UPV. The SCSIE (of the Universitat de Valencia) is also gratefully acknowledged for all the equipment used. NMR spectra were measured at the U26 facility of ICTS "NANBIOSIS" at the Universitat de Valencia.

[EN] Mesoporous silica nanoparticles capped with acetylcholinesterase, through boronic ester linkages, selectively release an entrapped cargo in the presence of acetylcholine., The authors acknowledge financial support from the Spanish Government (MAT2015-64139-C4-1-R, MAT2015-64139-C4-4-R and AGL2015-70235-C2-2-R) and the Generalitat Valenciana (PROMETEO2018/024). T. Godoy-Reyes is grateful to Generalitat Valenciana for her Santiago Grisollía fellowship. A. García-Fernández is grateful to the Spanish Government for her FPU fellowship

The introduction of stimuli-responsive cargo release capabilities on self-propelled micro- and nano- motors holds enormous potential in a number of applications in the biomedical field. Herein, we report the preparation of mesoporous silica nano-particles gated with pH-responsive supramolecular nanovalves and equipped with urease enzymes which act as chemical engines to power the nanomotors. The nanoparticles are loaded with different cargo molecules ([Ru(bpy)(3)]Cl-2 (bpy = 2,2'-bipyridine) or doxorubicin), grafted with benzimidazole groups on the outer surface, and capped by the formation of inclusion complexes between benzimidazole and cyclodextrin-modified urease. The nanomotor exhibits enhanced Brownian motion in the presence of urea. Moreover, no cargo is released at neutral pH, even in the presence of the biofuel urea, due to the blockage of the pores by the bulky benzimidazole:cyclodextrin-urease caps. Cargo delivery is only triggered on-command at acidic pH due to the protonation of benzimidazole groups, the dethreading of the supramolecular nanovalves, and the subsequent uncapping of the nanoparticles. Studies with HeLa cells indicate that the presence of biofuel urea enhances nanoparticle internalization and both [Ru(bpy)(3)]Cl-2 or doxorubicin intracellular release due to the acidity of lysosomal compartments. Gated enzyme-powered nanomotors shown here display some of the requirements for ideal drug delivery carriers such as the capacity to self-propel and the ability to "sense" the environment and deliver the payload on demand in response to predefined stimuli.

[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.

Mesoporous silica nanoparticles loaded with rhodamine B and capped with acetylcholinesterase are able to be selectively opened and deliver their cargo in the presence of nerve agent simulant diisopropyl fluorophosphate (DFP)., Financial support from the Spanish Government and FEDER funds (Project MAT2015-64139-C4-1) and the Generalitat Valenciana (Project PROMETEOII/2014/047) is gratefully acknowledged. L.P. is grateful to the Universitat Politecnica de Valencia for his grant.

A colon targeted drug delivery system for inflammatory bowel diseases (IBD), consisting in budesonide loaded mesoporous silica microparticles functionalized with a selective azo-molecular gate (M-Bud), has been evaluated for in vivo efficacy. Experimental colitis in male Wistar rats was induced by rectal instillation of 2,4,6-trinitrobenzenesulfonic acid (TNBS). M-Bud was orally administered to the rats as a suspension in water. Colon/body weight ratio, clinical activity score, and histological evaluation were used as inflammatory indices to measure the performance of the microparticles. The formulation was compared with a suspension prepared from the commercial drug Entocord®. Statistical analyses of all scores indicate that the controlled release of budesonide in colon from M-Bud showed efficacy similar to that of Entocord in the healing of induced colitis in rats.

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.

[EN] Nanoparticles have specific features (lipophilicity, surface charge, composition and size). Studies regarding the biological behavior of nanoparticles in diseases such diabetics and obesity are scarce. Here, we evaluated two nanoparticles: magnetic core mesoporous silica (MSN) (58 nm) and polycaprolactone (PCL) nanoparticle (280 nm) in obese mice. Changes in the biodistribution were observed, especially considering the mononuclear phagocyte system (MPS), and the visceral fat tissue. Nonetheless, our data corroborates the influence of size in the biodistribution in obese animals, supporting that smaller nanoparticles, may show a higher tissue deposition at spleen, due the associated splenomegaly and the complications arising from this state. Finally, our study demonstrated that, in obesity, probably due the low-grade inflammatory state associated with metabolic syndrome a difference in accumulation of nanoparticles was found, with profound impact in the tissue deposition of nanoparticles., The authors would like to thank the National Scientific and Technological Research Council (CNPQ) - no. 400018/2016-0 and the Rio de Janeiro State Research Foundation (FAPERJ) - E-26/102.940/2012 for funding. Authors also gratefully acknowledge the financial support from the Ministerio de Economía y Competitividad (Project MAT2012-38429-C04-01) and the Generalitat Valenciana (project PROMETEO/2009/016) for support.

[EN] Mesoporous silica microparticles were prepared, loaded with the dye safranin O (M-Saf) or with the drug budesonide (M-Bud) and capped by the grafting of a bulky azo derivative. Cargo release from M-Saf at different pH values (mimicking those found in the gastrointestinal tract) in the absence or presence of sodium dithionite (a reducing agent mimicking azoreductase enzyme present in the colon) was tested. Negligible safranin O release was observed at pH 6.8 and 4.5, whereas a moderate delivery at pH 1.2 was noted and attributed to the hydrolysis of the urea bond that linked the azo derivative onto the external surface of the inorganic scaffold. Moreover, a marked release was observed when sodium dithionite was present and was ascribed to the rupture of the azo bond in the molecular gate. Budesonide release from M-Bud in the presence of sodium dithionite was also assessed by ultraviolet-visible spectroscopy and high performance liquid chromatography measurements. In addition, preliminary in vivo experiments with M-Saf carried out in mice indicated that the chemical integrity of the microparticles remained unaltered in the stomach and the small intestine, and safranin O seemed to be released in the colon., We thank the Spanish Government (projects MAT2015-64139-C4-4-R, MAT2015-64139-C4-2-R and MAT2015-64139-C4-1-R) and Generalitat Valenciana (project PROMETEOII/2014/047 and project AICO/2017/093) for financial support.

[EN] Magnetic mesoporous silica microparticles were loaded with safranin O (S1) and with hydrocortisone (S2) and the outer surface functionalized with a bulky azo derivative bearing urea moieties. Aqueous suspensions of both solids at pH 7.4 showed negligible payload release whereas a marked delivery was observed in the presence of sodium dithionite due to the rupture of the azo bonds. Besides, a moderate cargo release was observed at acidic pH due to the hydrolysis of the urea bonds that linked the azo derivative onto the external surface of the inorganic scaffolds. In vitro digestion models showed that S1 and S2 microparticles could be used for the controlled release of payload in the reducing colon environment (in which azoreductase enzymes are present). On the other hand, in vivo pharmacokinetic studies in rats showed that safranine O release from S1 microparticles was concentrated in colon. The performance of S2 microparticles for the treatment of colitis in rats (induced by oral administration of a 2,4,6-trinitrobenzenesulfonic acid solution) was tested. The controlled release of hydrocortisone from S2 in the colon of injured rats induced marked reduction in colon/body weight ratio and in clinical activity score. Also, histological studies showed a marked decrease in inflammation followed by intensive regeneration and almost normal mucosal structure of the individuals treated with S2. Besides, the use of a magnetic belt increased the therapeutic performances of S2 due to an enhanced retention time of the particles in the colon., 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. AHT thanks to the Spanish MEC for his FPU grant. The authors also thank the Electron Microscopy Service at the Universitat Politecnica de Valencia for support. SCSIE (Universitat de Valencia) is also gratefully acknowledged for all the equipment employed. NMR was registered at the U26 facility of ICTS "NANBIOSIS" at the Universitat de Valencia. The authors thanks Dr. L. A. Villaescusa for his helpful discussion about the 1H NMR analysis of the composition of loaded and functionalized supports.

[EN] Magnetic micro-sized mesoporous silica particles were used for the preparation of a gated material able to release an entrapped cargo in the presence of an azo-reducing agent and, to some extent, at acidic pH. The magnetic mesoporous microparticles were loaded with safranin O and the external surface was functionalized with an azo derivative 1 (bearing a carbamate linkage) yielding solid S1. Aqueous suspensions of S1 at pH 7.4 showed negligible safranin O release due to the presence of the bulky azo derivative attached onto the external surface of the inorganic scaffold. However, in the presence of sodium dithionite (azoreductive agent), a remarkable safranin O delivery was observed. At acidic pH, a certain safranin O release from S1 was also found. The pH-triggered safranin O delivery was ascribed to the acid-induced hydrolysis of the carbamate moiety that linked the bulky azo derivatives onto the mesoporous inorganic magnetic support. The controlled release behavior of S1 was also tested using a model that simulated the gastro intestinal tract., We thank the Spanish Government (projects MAT2015-64139-C4-1-R and AGL2015-70235C2-2-R (MINECO/FEDER)) and the Generalitat Valenciana (project PROMETEOII/2014/047) for support. AHT thanks to the Spanish MEC for his FPU grant. The authors also thank the Electron Microscopy Service at the Universitat Politecnica de Valencia for support. SCSIE (Universitat de Valencia) is also gratefully acknowledged for all the equipment employed. NMR was registered at the U26 facility of ICTS "NANBIOSIS" at the Universitat de Valencia. The authors thanks L.A. Villaescusa for his helpful discussion about the 1H-NMR analysis of the composition of loaded and functionalized supports.

[EN] Biocompatible ZnS-based nanocrystals capped with 4-mercaptophenylboronic acid (ZnS@B) have been size-designed as excellent pH responsive gatekeepers on mesoporous silica nanoparticles (MSNs), which encapsulate fluorophore safranin O (S2-Sap or anticancer drug epirubicin hydrochloride (S2-Epi) for delivery applications in cancer cells. In this novel hybrid system, the gate mechanism consists of reversible pH-sensitive boronate ester moieties linking the nanocrystals directly to the alcohol groups from silica surface scaffold, avoiding tedious intermediate functionalization steps. The similar to 3 nm size of the ZnS@B nanocrystals was tailored to allow efficient sealing of the pore voids and achieve a "zero premature cargo release" at neutral pH (7.4). The system selectively released the cargo in acidic conditions (pH 5.4 and 3.0) because of the hydrolysis of the boronate esters, which unblocked the pore voids. Delivery of the cargo by off-on cycles was demonstrated by changes in pH from 7.4 to 3.0, showing its potential pH-switching behavior. Cellular uptake of these nanocarriers within human cervix adenocarcinoma (HeLa) cells was achieved and the controlled release of the chemotherapeutic drug epirubicin was shown to occur within the endogenous endosomal/lysosomal acidified cancer cell microenvironment and further diffused into the cytosol. Cytotoxicity tests done on the mesoporous support without cargo and covalently linked with ZnS@B nanocrystals as caps were negative, suggesting that the proposed system is biocompatible and can be considered as a very promising drug nanocarrier., The authors acknowledge P. Oberhumer from Centre for Nano- and Surface Analytics (ZONA) for the SEM and TEM measurements; Prof. A. Rastelli from Semiconductor Physics Division, Institute of Semiconductor and Solid State Physics, for helping in the Bohr radius calculations for excitons in ZnS; and the Prof. G. Knor from Institut fur Anorganische Chemie, for the access to the fluorescence spectrometer, all located at Johannes Kepler University Linz. M. Kleindienst is acknowledged for her drawing contribution (Scheme 1,,). R.M.-M. and F.S. express their gratitude to the Spanish government (MAT2015-64139-C4-1-R (MINECO/FEDER)) and the Generalitat Valencia (PROMETEOII/2014/047) for support. A.G-F. is grateful to the Spanish government for an FPU grant.

[EN] Apoptotic signaling pathways are altered in numerous pathologies such as cancer. In this scenario, caspase-9/PP2Ac alpha interaction constitutes a key target with pharmacological interest to re-establish apoptosis in tumor cells. Very recently, a short peptide (C9h) known to disrupt caspase-9/PP2Ac alpha interaction with subsequent apoptosis induction was described. Here, we prepared two sets of mesoporous silica nanoparticles loaded with safraninO (S2) or with C9h peptide (S4) and functionalized with epsilon-polylysine as capping unit. Aqueous suspensions of both nanoparticles showed negligible cargo release whereas in the presence of pronase, a marked delivery of safraninO or C9h was observed. Confocal microscopy studies carried out with HeLa cells indicated that both materials were internalized and were able to release their entrapped cargos. Besides, a marked decrease in HeLa cell viability (ca. 50%) was observed when treated with C9h-loaded S4 nanoparticles. Moreover, S4 provides peptide protection from degradation additionally allowing for a dose reduction to observe an apoptotic effect when compared with C9h alone or in combination with a cell-penetrating peptide (i.e., Mut3DPT-C9h). Flow cytometry studies, by means of Annexin V-FITC staining, showed the activation of apoptotic pathways in HeLa as a consequence of S4 internalization, release of C9h peptide and disruption of caspase-9/PP2Ac alpha interaction., The authors wish to express their gratitude to the Spanish government (Projects MAT2015-64139-C4-1, SAF2012-31405, SAF2015-67077-R, AGL2015-70235-C2-2-R (MINECO/FEDER)), the Generalitat Valencia (Projects PROMETEOII/2014/047, PROMETEO/2012/061) and the CIBER-BBN for their support. C.T. is grateful to the Spanish Ministry of Science and Innovation for her Ph.D. fellowship.

[EN] Boron chemistry has raised much interest because, despite the difference between necessities and toxicity being very narrow, it is still widely used in industrial processes. In a previous work we reported an adsorbent for boron extraction from water by the functionalisation of a UVM-7 mesoporous silica matrix with gluconamide moieties. The ability of this material to adsorb boron is based on its well-known affinity for coordinating the cis-diols present in attached saccharide. Although much research on the formation of boron esters with sugars and sugar derivatives in solution has been done, very few reports have dealt with the adsorption mechanism of boron onto functionalised materials in the solid state. Hence an in-depth study of the adsorption process was conducted in this paper. For this purpose, several solids with increasing boron contents were prepared from the gluconamide-functionalised UVM-7 material and an isothermal boron adsorption curve was obtained. The B-11 and C-13 MAS NMR techniques were used to characterise the obtained solids, and the simulation of the boron NMR and isothermal adsorption combined data was accomplished to enlighten the boron adsorption process. A model with three different coordination environments, two possible adsorption sites and the presence of oligomeric boron species allowed us to reproduce not only the isothermal boron adsorption curve, but also the evolution of the integrated areas for the signals in the B-11 MAS NMR spectra obtained for the different boron-containing gluconamide-functionalised UVM-7 materials., Financial support from the Spanish Government (Project MAT2009-14564-C04-01 and MAT2012-38429-C04-01) and the Generalitat Valenciana (Project PROMETEO/2009/016) is gratefully acknowledged. C.S. thanks the MICINN for a predoctoral fellowship.

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.

Due to the narrowrange between boron necessities and toxicity in the environment, there is a high interest in the design of effective boron remediation procedures. We have previously reported a promising boron adsorptionmaterial based on the affinity of boron aqueous species for cis-diol groups that were anchored on differentmesoporous silica matrices.However, the small particle size of these systemsmakes themdifficult to be applied on real remediation situations. In this context we report herein a novel systemfor boron adsorption fromaqueous solutions inwhich the high boron affinity for functionalized mesoporousmaterials is combined with themechanical properties of ceramic foams as macroscopic supports. The efficiency of these new composites for boron removal is very high and comparable with the parent microparticulated adsorbent., Financial support from the Spanish Government (Project MAT2009-14564-C04-01 and MAT2009-14564-C04-04, and MAT2012-38429-C04-01 and MAT2012-38429-C04-02) and the Generalitat Valenciana (Project PROMETEO/2009/016) is gratefully acknowledged. C.S. thanks the MICINN for a predoctoral fellowship.

[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.

[EN] The use of monoclonal antibodies (Mab) in the current medicine is increasing. Antibody-drug conjugates (ADCs) represents an increasingly and important modality for treating several types of cancer. In this area, the use of Mab associated with nanoparticles is a valuable strategy. However, the methodology used to calculate the Mab entrapment, efficiency and content is extremely expensive. In this study we developed and tested a novel very simple one-step methodology to calculate monoclonal antibody entrapment in mesoporous silica (with magnetic core) nanoparticles using the radiolabeling process as primary methodology. The magnetic core mesoporous silica were successfully developed and characterised. The PXRD analysis at high angles confirmed the presence of magnetic cores in the structures and transmission electron microscopy allowed to determine structures size (58.9 +/- 8.1 nm). From the isotherm curve, a specific surface area of 872 m(2)/g was estimated along with a pore volume of 0.85 crn(3)/g and an average pore diameter of 3.15 nm. The radiolabeling process to proceed the indirect determination were well-done. Trastuzumab were successfully labeled (>97%) with Tc-99m generating a clear suspension. Besides, almost all the Tc-99m used (labeling the trastuzumab) remained trapped in the surface of the mesoporous silica for a period as long as 8 h. The indirect methodology demonstrated a high entrapment in magnetic core mesoporous silica surface of Tc-99m-traztuzumab. The results confirmed the potential use from the indirect entrapment efficiency methodology using the radiolabeling process, as a one-step, easy and cheap methodology. (C) 2018 Elsevier B.V. All rights reserved., The authors would like to thank the National Scientific and Technological Research Council (CNPQ) and the Rio de Janeiro State Research Foundation (FAPERJ) for funding. Authors also gratefully acknowledge the financial support from the Ministerio de Economia y Competitividad (Project MAT2012-38429-004-01) and the Generalitat Valenciana (project PROMETEO/2009/016) for support.

[EN] The development of easy and affordable methods for the detection of cyanide is of great significance due to the high toxicity of this anion and the potential risks associated with its pollution. Herein, optical detection of cyanide in water has been achieved by using a hybrid organic-inorganic nanomaterial. Mesoporous silica nanoparticles were loaded with [Ru(bipy)(3)](2+), functionalized with macrocyclic nickel(II) complex subunits, and capped with a sterically hindering anion (hexametaphosphate). Cyanide selectively induces demetallation of nickel(II) complexes and the removal of capping anions from the silica surface, allowing the release of the dye and the consequent increase in fluorescence intensity. The response of the capped nanoparticles in aqueous solution is highly selective and sensitive towards cyanide with a limit of detection of 2 mu M., We thank the Spanish Government (projects MAT2015-64139-C4-1-R and AGL2015-70235-C2-2-R (MINECO/FEDER, UE)) and the Generalitat Valenciana (project PROMETEOII/2014/047) for support.

The use of nanosystems as diagnosing and therapy systems is increasing each year. There are several nanosystems available and the most prominent ones are: mesoporous silica, nanoemulsion and polymeric nanoparticles. With characteristics like low toxicology, and easy-producing process they have advantages when compared with the traditional system used, as they show specific targeting, controlled release, and higher penetration. In this study we tested three different nanocarriers (polymeric nanoparticles, nanoemulsion and mesoporous silica) containing phthalocyanineas possible PDT drugs (nanodrugs). They were tested in vitro and in vivo: cells and healthy mice, respectively, in order to understand the biological behavior and reach the initial conclusions. The results in cells showed that a dose response was observed with different concentrations of the three nanocarriers. The results in animal showed that all nanosystems have potential for application in PDT, since they were able to produce a visible effect in healthy animals.

[EN] Organic-inorganic hybrid nanomaterials offer extremely valuable tools for monitoring many types of analytes in solution. Within this framework, aptamer-based nanomaterials for heavy metal detection are still very scarce. Herein, a novel sensing nanoprobe for the selective and sensitive detection of As(III) based on the combination of aptamers with mesoporous silica nanoparticles has been developed. The efficiency of the sensor is demonstrated in environmental conditions, showing a great potential in As(III) monitoring assays., The authors thank 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). M.O. is grateful to the Universitat Politecnica for her PhD grant. A.B. thanks the Spanish Government for the finantial support "Juan de la Cierva-Incorporacion" (IJCI-2014-21534). C.C. thanks the Generalitat Valenciana for her postdoctoral contract VALi+D.

[EN] Two different acetylcholinesterase (AChE)-capped mesoporous silica nanoparticles (MSNs), S1-AChE and S2-AChE, were prepared and characterized. MSNs were loaded with rhodamine B and the external surface was functionalized with either pyridostigmine derivative P1 (to yield solid S1) or neostigmine derivative P2 (to obtain S2). The final capped materials were obtained by coordinating grafted P1 or P2 with AChE ' s active sites (to give S1-AChE and S2-AChE, respectively). Both materials were able to release rho-damine B in the presence of diisopropylfluorophosphate (DFP) or neostigmine in a concentration-dependent manner via the competitive displacement of AChE through DFP and neostigmine coordination with the AChE ' s active sites. The responses of S1-AChE and S2-AChE were also tested with other enzyme inhibitors and substrates. These studies suggest that S1-AChE nanoparticles can be used for the selective detection of nerve agent simulant DFP and paraoxon., Financial support from the Spanish Government and FEDER funds (Project MAT2015‐64139‐C4‐1‐R, AGL2015‐70235‐C2‐2‐R) and the Generalitat Valencia (Project PROMETEOII/2014/047) is gratefully acknowledged. Ll. P. is grateful to the Universitat Politécnica de Valencia for his grant.

[EN] This review summarises examples of capped mesoporous silica materials for controlled delivery that use enzymes as external triggers or functional components of the gating ensemble., Financial support from the Spanish Government and FEDER funds (Project MAT2015-64139-C4-1) and the Generalitat Valencia (Project PROMETEOII/2014/047) is gratefully acknowledged. A. Llopis-Lorente is grateful to "La Caixa'' Banking Foundation for his PhD fellowship. B. Lozano-Torres is grateful to the Spanish Ministry of Economy and Competitiveness (MEC) for her FPU grant. Also A. Bernardos thanks the Spanish MEC for her Juan de la Cierva Contract.

[EN] Inflammation processes are difficult to manage, especially in certain diseases like cancer. The prognostic of the patient may change drastically during the therapy if an inflammation process occurs. In this direction several research groups are trying to develop new agents for treatment and imaging of the inflammation process in order to improve patients prognostics. In this study we have developed and evaluated two possible imaging agents for nuclear medicine procedure using mesoporous silica nano particles as the carrier system. In this direction we developed mesoporous silica nanoparticles loaded with betamethasone and mesoporous silica nanoparticles conjugated with dexamethasone nano particles, both labeled with technetium-99m (Tc-99m) and compared the biodistribution (pharmacokinetic) profile of the two formulations in an inflammation model of carrageenan-induced pleurisy in Wistar rats. The results demonstrated that in both cases the mesoporous silica was able to show the inflammation site with a high accumulation in the inflammatory site with great renal clearance. Considering the fact that radiopharmaceuticals are considered first-order drugs the pharmacokinetics profile are the same of the biodistribution. The cytotoxicity assay demonstrated that the use of mesoporous silica nanoparticles conjugated with dexamethasone nanoparticles is safer when compared to the mesoporous silica nanoparticles loaded with betamethasone. Nevertheless, both formulations may be used for inflammation process imaging. (C) 2016 Elsevier Inc. All rights reserved., The authors would like to thank the National Scientific and Technological Research Council CHAMADA MCTI/CNPQ/CBAB No 07/2014 (CNPQ) and the Rio de Janeiro State Research Foundation (FAPERJ) for funding.Authors also gratefully acknowledge the financial support from theMinisterio de Economia y Competitividad (Project MAT2012-38429-C04-01) and the GeneralitatValenciana (project PROMETEO/2009/016) for support.

[EN] The mononuclear phagocytic system is a key participant determining the half-life of nanoparticles (NPs) in the bloodstream and influencing active targeting. Several strategies to extend the circulation time of nanoparticles and to reduce MPS (Mononuclear Phagocyte System) uptake have been developed so far. Here we evaluated the potential of albumin coated-mesoporous silica nanoparticles to overcome MPS clearance in a mouse model of endometrioses. We found that human albumin bath was able to reduce unspecific uptake by liver and spleen but reduced accumulation of NPs to endometriosis site. Our data suggest that although human albumin bath may help to overcome MPS clearance of NPs, it affects NPs uptake by the target site. (C) 2017 Elsevier Inc. All rights reserved., The authors would like to thank the National Scientific and Technological Research Council (CNPQ) and the Rio de Janeiro State Research Foundation (FAPERJ) for funding.Authors also gratefully acknowledge the financial support from the Ministerio de Economia y Competitividad (Project MAT2012-38429-004-01) and the Generalitat Valenciana (project PROMETEO/2009/016) for support.

[EN] Mucin 1 (MUC1) is a cell surface protein overexpressed in breast cancer. Mesoporous silica nanoparticles (MSNs) loaded with safranin O, functionalized with aminopropyl groups and gated with the negatively charged MUC1 aptamer have been prepared (S1-apMUC1) for specific targeting and cargo release in tumoral versus non-tumoral cells. Confocal microscopy studies showed that the S1-apMUC1 nanoparticles were internalized in MDA-MB-231 breast cancer cells that overexpress MUC1 receptor with subsequent pore opening and cargo release. Interestingly, the MCF-10-A non-tumorigenic breast epithelial cell line that do not overexpress MUC1, showed reduced (S1-apMUC1) internalization. Negligible internalization was also found for S1-ap nanoparticles that contained a scrambled DNA sequence as gatekeeper. S2-apMUC1 nanoparticles (similar to S1-apMUC1 but loaded with doxorubicin) internalized in MDA-MB-231 cells and induced a remarkable reduction in cell viability. Moreover, S1-apMUC1 nanoparticles radio-labeled with Tc-99m (S1-apMUC1-Tc) showed a remarkable tumor targeting in in vivo studies with MDA-MB-231 tumor-bearing Balb/c mice. (C) 2017 Elsevier Inc. All rights reserved., Financial support from the Spanish Government and FEDER funds (Project MAT2015-64139-C4-1) and the Generalitat Valenciana (Project PROMETEOII/2014/047) is gratefully acknowledged.

[EN] Aptamers have been used as recognition elements for several molecules due to their great affinity and selectivity. Additionally, mesoporous nanomaterials have demonstrated great potential in sensing applications. Based on these concepts, we report herein the use of two aptamer¿capped mesoporous silica materials for the selective detection of ochratoxin¿A (OTA). A specific aptamer for OTA was used to block the pores of rhodamine¿B¿loaded mesoporous silica nanoparticles. Two solids were prepared in which the aptamer capped the porous scaffolds by using a covalent or electrostatic approach. Whereas the prepared materials remained capped in water, dye delivery was selectively observed in the presence of OTA. The protocol showed excellent analytical performance in terms of sensitivity (limit of detection: 0.5¿0.05¿nm), reproducibility, and selectivity. Moreover, the aptasensors were tested for OTA detection in commercial foodstuff matrices, which demonstrated their potential applicability in real samples, 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. S.S. thanks the Instituto de Salud Carlos III and the European Social Fund for the financial support "Sara Borrell" (CD16/000237). A.B. thanks the Spanish Government for financial support by the "Juan de la Cierva-Incorporacion" (IJCI-2014-21534). The authors also thank the Electron Microscopy Service at UPV for support.