Estela Climent

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.

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)

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.

Chromogenic Detection of Nerve Agent Mimics by Mass Transport Control at the Surface of Bifunctionalized Silica Nanoparticles

Chemical warfare (CW) agents are toxic chemicals that have been used in several terrorist attacks in recent years. Among CW species, nerve agents are probably the most dangerous; their high toxicity and facile synthesis underscores the need to detect these lethal compounds with quick, reliable procedures. Analytical methods based on enzymatic assays and physical measurements have generally been used to detect these hazards. However, these protocols usually have limitations such as low selectivity, poor portability, and a certain level of complexity. In recent years, several chromogenic and fluorogenic sensors, and reagents for the detection of nerve agents have been described. For instance, approaches that involve perborate-mediated oxidation of organophosphorus agents, fluorescent probes based on polyethylene terephthalate (PET), assays that use oximate-containing derivatives, molecularly imprinted polymers, nanoparticles, carbon nanotubes, porous silicon, displacement-like procedures, and cyclization reactions in push–pull chromophores have been reported. Most of these protocols rely on changes in fluorescence properties, whereas few examples deal with color modulations. Colorimetric detection is particularly appealing because it uses low-cost, widely available instrumentation and allows assays to be detected with the naked eye. However, the development of selective, sensitive chromogenic probes for the detection of deadly chemical species is still rare. Given our interest in the design of novel hybrid organic– inorganic materials as probes, we focused on the preparation of a new optical test for the detection of nerve agent mimics based on nerve agent control of mass transport to the surface of functionalized silica nanoparticles. The chromogenic approach (Scheme 1) involves the use of silica nanoparticles that are functionalized with two different subunits— thiol groups (SH) and aliphatic alcohols (OH). The role of the

Selective, Highly Sensitive, and Rapid Detection of Genomic DNA by Using Gated Materials: Mycoplasma Detection

Financial support from the Spanish Government (MAT2009-14564-C04-01 and SAF2010 15512), the Generalitat Valenciana (PROM-ETEO/2009/016 and 2010/005) is gratefully acknowledged. E. C. thanks the Ministerio de Educacion for a fellowship. L. M. thanks Generalitat Valenciana for her Post-Doc VALI + D contract.

Selective opening of nanoscopic capped mesoporous inorganic materials with nerve agent simulants; an application to design chromo-fluorogenic probes

A hybrid nanoscopic capped mesoporous material, that is selectively opened in the presence of nerve agent simulants, has been prepared and used as a probe for the chromo-fluorogenic detection of these chemicals.

Towards Chemical Communication between Gated Nanoparticles

The design of comparatively simple and modularly configurable artificial systems able to communicate through the exchange of chemical messengers is, to the best of our knowledge, an unexplored field. As a proof-of-concept, we present here a family of nanoparticles that have been designed to communicate with one another in a hierarchical manner. The concept involves the use of capped mesoporous silica supports in which the messenger delivered by a first type of gated nanoparticle is used to open a second type of nanoparticle, which delivers another messenger that opens a third group of gated nanoobjects. We believe that the conceptual idea that nanodevices can be designed to communicate with one another may result in novel applications and will boost further advances towards cooperative systems with complex behavior as a result of the communication between simple abiotic individual components.

Enhanced Efficacy and Broadening of Antibacterial Action of Drugs via the Use of Capped Mesoporous Nanoparticles

Bug busters: A novel nanodevice consisting of mesoporous nanoparticles loaded with vancomycin and capped with ε-poly-L-lysine (ε-PL) was prepared and its interaction with different Gram-negative bacteria studied. A remarkable improvement in the efficacy of the antimicrobial drug ε-PL and a broadening of the antimicrobial spectrum of vancomycin is demonstrated.

A Rapid and Sensitive Strip-Based Quick Test for Nerve Agents Tabun, Sarin, and Soman Using BODIPY-Modified Silica Materials

Test strips that in combination with a portable fluorescence reader or digital camera can rapidly and selectively detect chemical warfare agents (CWAs) such as Tabun (GA), Sarin (GB), and Soman (GD) and their simulants in the gas phase have been developed. The strips contain spots of a hybrid indicator material consisting of a fluorescent BODIPY indicator covalently anchored into the channels of mesoporous SBA silica microparticles. The fluorescence quenching response allows the sensitive detection of CWAs in the μg m(-3) range in a few seconds.