Pedro Amorós

Controlled Delivery Using Oligonucleotide‐Capped Mesoporous Silica Nanoparticles

The design of delivery systems with “molecular locks” able to selectively release entrapped guests in the presence of target triggers has attracted great attention recently. As an alternative to traditional polymer-based delivery systems, mesoporous silica supports show unique properties such as a large load capacity, biocompatibility, and potential for the development of gated supports for on-command delivery applications. Recently, mesoporous-silica-based systems displaying controlled release have been reported relying on changes in pH, redox potential, and light for uncapping the pores. However, the use of mesoporous silica supports equipped with gatelike scaffoldings is still an incipient area of research. In particular, despite some recent reported gated mesoporous silica supports that can be uncapped using antigens or enzymes, there is an almost complete lack of mesoporous-silica-based devices designed to trigger cargo release involving biomolecules. Within this context, our interest in the development of gated materials motivated us to explore the possible design of new “bio-gates” able to respond selectively to “key” molecules. We focused our attention on the use of nucleotides. The proposed paradigm is represented in Scheme 1. In this work nanoparticles (ca. 100 nm) of mesoporous MCM-41 have been selected as the inorganic scaffold. The MCM-41 support is first loaded with a suitable guest (fluorescein), and then the external surface is functionalized with 3-aminopropyltriethoxysilane (APTS) to give the solid S1. Aminopropyl groups are partially charged at neutral pH in water and will interact with negatively charged oligonucleotides, resulting in the closing of the mesopores. The opening protocol will be expected to occur by a highly effective displacement reaction in the presence a target complementary strand; this will result in hybridization of the two oligonucleotides, the uncapping of the pores, and release of the entrapped cargo. The mesoporous solid S1 containing fluorescein in the pore voids and functionalized on the external surface with APTS groups was characterized following standard procedures (see the Supporting Information). The powder X-ray diffraction (XRD) pattern of siliceous MCM-41 nanoparticles as synthesized (Figure 1, curve a) shows four low-angle reflections typical of a hexagonal array which can be indexed as (100), (110), (200), and (210) Bragg peaks. A significant displacement of the (100) peak in the XRD pattern of the MCM-41 calcined nanoparticles is evident in curve b. Finally, curve c corresponds to the XRD pattern of S1. The (100), (110), and (200) peaks are clearly observed strongly suggesting that the dye loading and further functionalization with Scheme 1. Representation of the gated material S1 functionalized with 3-aminopropyltriethoxysilane and capped with a single-stranded oligonucleotide (O1). The delivery of the entrapped guest (fluorescein) is selectively accomplished in the presence of the complementary oligonucleotide (O2). The sequence of the oligonucleotides O1 and O2 is shown.

Controlled Delivery Systems Using Antibody-Capped Mesoporous Nanocontainers

This paper describes the design of new controlled delivery systems consisting of a mesoporous support functionalized on the pore outlets with a certain hapten able to interact with an antibody that acts as a nanoscopic cap. The opening protocol and delivery of the entrapped guest is related by a displacement reaction involving the presence in the solution of the antigen to which the antibody is selective. As a proof-of-the-concept, the solid MCM-41 was selected as support and was loaded with the dye [Ru(bipy)(3)]Cl(2). Then a suitable derivative of the hapten 4-(4-aminobenzenesulfonylamino)benzoic acid was anchored on the outer surface of the mesoporous support (solid S1). Finally the pores were capped with a polyclonal antibody for sulfathiazole (solid S1-AB). Delivery of the dye in the presence of a family of sulfonamides was studied in phosphate-buffered saline (PBS; pH 7.5). A selective uncapping of the pores and dye delivery was observed for sulfathiazole. This delivery behavior was compared with that shown by other solids that were prepared as models to assess the effect of the hapten and its interaction with antibody in the dye delivery control in the presence of the antigen.

Enzyme-mediated controlled release systems by anchoring peptide sequences on mesoporous silica supports.

We thank the Spanish Government (projects MAT2009-14564-C04, CB07/01/2012, and BIO2007 60066), the Generalitat Valencia (project PROMETEO/2009/016, PROMETEO/2010/005), and the CIBER-BBN for their support.

Generalised syntheses of ordered mesoporous oxides: the atrane route

Abstract A new simple and versatile technique to obtain mesoporous oxides is presented. While implying surfactant-assisted formation of mesostructured intermediates, the original chemical contribution of this approach lies in the use of atrane complexes as precursors. Without prejudice to their inherent unstability in aqueous solution, the atranes show a marked inertness towards hydrolysis. Bringing kinetic factors into play, it becomes possible to control the processes involved in the formation of the surfactant–inorganic phase composite micelles, which constitute the elemental building blocks of the mesostructures. Independent of the starting compositional complexity, both the mesostructured intermediates and the final mesoporous materials are chemically homogeneous. The final ordered mesoporous materials are thermally stable and show unimodal porosity, as well as homogeneous microstructure and texture. Examples of materials synthesised on account of the versatility of this new method, including siliceous, non siliceous and mixed oxides, are presented and discussed.

Finely Tuned Temperature-Controlled Cargo Release Using Paraffin-Capped Mesoporous Silica Nanoparticles†

Financial support from the Spanish Government (projects MAT2009-14564-C04-01 and SAF2010-15512) and the Generalitat Valenciana (projects PROMETEO/2009/016 and PROMETEO/2010/005) is gratefully acknowledged. L. M. thanks the Generalitat Valenciana for a VALi + d postdoctoral contract. We thank UPV electron microscopy and CIPF confocal microscopy services for technical support.

A Mesoporous 3D Hybrid Material with Dual Functionality for Hg2+ Detection and Adsorption

Dual-function hybrid material U1 was designed for simultaneous chromofluorogenic detection and removal of Hg(2+) in an aqueous environment. Mesoporous material UVM-7 (MCM41 type) with homogeneously distributed pores of about 2-3 nm in size, a large specific surface area exceeding 1000 m(2) g(-1), and nanoscale particles was used as an inorganic support. The mesoporous solid is decorated with thiol groups that were treated with squaraine dye III to give a 2,4-bis(4-dialkylaminophenyl)-3-hydroxy-4-alkylsulfanylcyclobut-2-enone (APC) derivative that is covalently anchored to the inorganic silica matrix. The solid was characterised by various techniques including X-ray diffraction, transmission electron microscopy, Raman spectroscopy, and nitrogen adsorption. This hybrid solid is the chemodosimeter for Hg(2+) detection. Hg(2+) reacts with the APC fragment in U1 with release of the squaraine dye into the solution, which turns deep blue and fluoresces strongly. Naked-eye Hg(2+) detection is thus accomplished in an easy-to-use procedure. In contrast, U1 remains silent in the presence of other thiophilic transition metal ions, alkali and alkaline earth metal ions, or anions ubiquitously present in water such as chloride, carbonate, sulfate, and phosphate. Material U1 acts not only as chemodosimeter that signals the presence of Hg(2+) down to parts-per-billion concentrations, but at the same time is also an excellent adsorbent for the removal of mercury cations from aqueous solutions. The amount of adsorbed mercury ranges from 0.7 to 1.7 mmol g(-1), depending on the degree of functionalisation. In addition, hybrid material U1 can be regenerated for both sensing and removal purposes. As far as we know, U1 is the first example of a promising new class of polyfunctional hybrid supports that can be used as both remediation and alarm systems by selective signalling and removal of target species of environmental importance. Model compounds based on silica gel (G1), fumed silica (F1), and micrometre-sized MCM-41 scaffolds (M1) were also prepared and studied for comparative purposes.

The determination of methylmercury in real samples using organically capped mesoporous inorganic materials capable of signal amplification.

Mercury exists in the environment in a variety of compounds, and the toxicity depends on the chemical species. Organomercury derivatives, especially methylmercury (CH3Hg ), are more toxic than inorganic or elemental mercury. Methylmercury is rarely emitted anthropogenically, but usually formed naturally through biomethylation of mercury, often of anthropogenic origin. Methylmercury subsequently bio-accumulates through the food chain, for example in the tissue of fish, in which methylmercury concentrations are frequently found that exceed the maximum levels recommended by the Environmental Protection Agency (EPA) and the World Health Organization (WHO) for human consumption (0.1 and 0.23 mg (kg body weight) 1 d ). Methylmercury exposure in adults has been linked to cardiovascular diseases, autoimmune effects, hearing impairment, blindness, and death. In a number of cases, mercury intoxication is related to the consumption of fish. Several analytical methods have been described for the determination of methylmercury in biological samples. For example, gas chromatography (GC) with electron capture detection (ECD) or inductively coupled plasma mass spectrometry (ICP-MS) and high performance liquid chromatography (HPLC) with elemental or ICP-MS detection have been extensively used. As an alternative to these technically sophisticated methods, which require a laboratory setting, the development of more simple procedures for in situ and rapid screening applications that are based on optical, electrochemical, or gravimetric procedures have recently received considerable attention; these methods involve in part biological species as active sensing elements. Regarding the development of chromoand fluorogenic indication systems for mercury derivatives, a large number of examples have been reported for the inorganic form (Hg), but few studies have targeted CH3Hg . Furthermore, most of these studies were unable to discriminate between Hg and CH3Hg + and did not involve the determination of the analyte(s) in relevant samples or matrices such as fish. Chemically, the great majority of the reported approaches rely on indicator molecules that either bind 17a] or react with Hg to yield the desired change in color or fluorescence. Only very recently, alternative procedures involving organic, inorganic, or hybrid materials have been proposed, which are promising in their performance. Our interest in the latter type of materials motivated us to explore bioinspired strategies toward new signaling models. For mercury indication, we combined our experience in Hg sensing and supramolecular hybrid materials design and developed an organically capped mesoporous inorganic material for selective CH3Hg + determination through signal amplification. Inspired by gated ion channels and pumps, the proposed sensing mechanism relies on the opening of a pore that is controlled by the interaction of a certain molecular stimulus (the target species, CH3Hg ) at the receptors that close the gate. Although this reaction itself can already induce an optical response, a second process is implemented in the system that leads to strong signal amplification: the pores of the hybrid are loaded with a large amount of dye molecules, which are only liberated upon analyte-induced opening of the pores. To date, apart from a few examples of analyte-induced pore blockage, pore-opening methods for sensing applications have not been reported. The sensing procedure is shown in Scheme 1. The inorganic support is a calcined MCM-41 mesoporous solid that features homogeneous porosity, facile surface functionalization, inertness, and a high loading capacity. The solid is first loaded with a dye (safranine O) and is then capped with 2,4-bis(4-dialkylaminophenyl)-3-hydroxy-4-alkylsulfanylcyclobut-2-enone (APC) groups. The APC moieties are [*] E. Climent, Dr. M. D. Marcos, Prof. R. Mart nez-M ez, Dr. F. Sancen n, Dr. J. Soto Instituto de Reconocimiento Molecular y Desarrollo Tecnol gico Centro Mixto Universidad Polit cnica de Valencia—Universidad de Valencia, Departamento de Qu mica Universidad Polit cnica de Valencia Camino de Vera s/n, 46022 Valencia (Spain) Fax: (+ 34)96-387-9349 E-mail: rmaez@qim.upv.es and CIBER de Bioingenier a, Biomateriales y Nanomedicina (CIBER-BBN)

Anthrylmethylamine functionalised mesoporous silica-based materials as hybrid fluorescent chemosensors for ATP

A number of functionalised mesoporous solids containing anchored anthrylmethylamine groups have been prepared using different co-hydrolysis or grafting synthetic routes. The solids have been characterised using standard solid-state techniques. Solids with a low loading of the anthrylmethylamine probe show typical well defined and structured emission bands centred at ca. 415 nm. Addition of ATP to suspensions of these solids at pH 2.8 resulted in a quenching of the anthracene emission. These solids showed a cooperative effect that resulted in quite a remarkable improvement in ATP response with respect to the free anthrylmethylamine probe in solution. Certain prepared solids showed a remarkable detection limit for ATP detection in the micromolar range. An equation based on a Langmuir-type analysis has been developed and used to obtain binding constants (adsorption constants) for the interaction of the solids with ATP and with some related anions. Some other solids containing larger amounts of anthrylmethylamine groups have also been prepared. In these cases a dual monomer–excimer fluorescence emission was observed. ATP addition to these solids resulted in an enhancement of the excimer emission band.

Enhanced surface area in thermally stable pure mesoporous TiO2

Abstract We describe here for the first time the surfactant-assisted synthesis of thermally stable mesoporous pure TiO 2 having a high surface area. Our synthetic approach to the chemistry of this system is based on the equilibrium between the hydrolysis and condensation reactions of the inorganic species and the organic–inorganic self-assembling processes. The use of titanatrane complexes helps to retard the hydrolysis and condensation reactions, thus allowing us to overcome the difficulties in preparing titanium dioxide mesoporous materials starting from highly reactive Ti-alkoxides. The mesoporous material has been characterized by TEM, XRD and N 2 adsorption–desorption isotherms and displays a typical wormhole-like pore structure.

An aptamer-gated silica mesoporous material for thrombin detection

An aptamer-capped mesoporous material for the selective and sensitive detection of α-thrombin in human plasma and serum has been prepared and characterised.