María D. Marcos

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.

Temperature-controlled release by changes in the secondary structure of peptides anchored onto mesoporous silica supports

Changes in the conformation of a peptide anchored onto the external surface of mesoporous silica nanoparticles have been used to design novel temperature-controlled delivery systems.

Selective and Sensitive Chromofluorogenic Detection of the Sulfite Anion in Water Using Hydrophobic Hybrid Organic–Inorganic Silica Nanoparticles

In water and wine: Chromofluorogenic detection of the sulfite anion in pure water was accomplished by using a new hybrid organic-inorganic material that contained a probe entrapped in hydrophobic biomimetic cavities. This material was used for the detection of sulfite in red wine.

Hybrid materials with nanoscopic anion-binding pockets for the colorimetric sensing of phosphate in water using displacement assays.

Mesoporous amino-functionalised solids containing certain dyes have been used as suitable anion hosts in displacement assays for the colorimetric signalling of phosphate in water.

A Photoactivated Molecular Gate

The authors thank the Spanish Government (project: MAT2009-14564-C04), the Generalitat Valenciana (project: PROMETEO/2009/016) and the CIBER-BBN for their support. A.A. also thanks the Generalitat Valenciana for his Santiago Grisolia fellowship.

Chromogenic silica nanoparticles for the colorimetric sensing of long-chain carboxylates

Silica nanoparticles functionalized with chromogenic spirobenzopyran and thiourea subunits show selective colour changes in the presence of certain long-chain carboxylates.

A new functionalised oligopyridine ligand containing ferrocene as a ball-bearing spacer for metallosupramolecular chemistry

Abstract A new supramolecular building-block in which a ferrocene moiety has been used as a spacer linking two terpyridyl units has been prepared. The new multidentate ligand 1,1′-bis(2,2′:6′,2″-terpyridin-4′-yl)ferrocene (tft) incorporates two tridentate metal-binding domains. The ligand has been synthesised from ferrocene-1,1′-dicarbaldehyde and 2-acetylpyridine in a two- stage procedure. The reaction of ferrocene-1,1′-dicarbaldehyde with 2-acetylpyridine yields the bis-chalcone 1,1′-[3-oxo-3-(2- pyridyl)prop-2-en-yl]ferrocene which has been structurally characterised: monoclinic, space group P21/c (No. 14) with a=13.126(3), b=10.470(2), c=15.642(3) A, β=111.62(3)° and Z=4, R1 0.052 (F>4σ(F), for 1611 reflections) and R2 0.125 (all data). The cyclopentadienyl rings of the ferrocene are eclipsed and the two 2,2′:6′,2″-terpyridinyl moieties are in a stacked coplanar conformation. The reaction of this chalcone with N-[1-oxo-2-(2-pyridyl)ethyl]pyridinium iodide and ammonium acetate yielded the new ligand as an orange solid which was structurally characterised: monoclinic, space group P21/c (No. 14), a=13.268(3), b=18.147(4), c=12.458(2) A, β=90.73(3)° and Z=4, R1 0.077 (F>4σ,(F), for 2041 reflections) and R2 0.217 (all data). Once again, the cyclopentadienyl rings of the ferrocene are eclipsed and the two 2,2′:6′,2″-terpyridinyl moieties are in a stacked coplanar conformation.

Tetrathiafulvalene-capped hybrid materials for the optical detection of explosives.

Mesoporous silica microparticles capped with TTF moieties and containing a ruthenium dye in the pores were used for the turn-on optical detection of the nitroaromatic explosives Tetryl and TNT via a selective pore uncapping and release of the entrapped dye.

Polymer Composites Containing Gated Mesoporous Materials for On-Command Controlled Release

Polyamidic nanofibrous membranes containing gated silica mesoporous particles, acting as carriers, are described as novel hybrid composite materials for encapsulation and on-command delivery of garlic extracts. The carrier system consists of MCM-41 solids functionalized in the outer surface, with linear polyamines (solid P1) and with hydrolyzed starch (solid P2), both acting as molecular gates. Those particles were adsorbed on electospun nylon-6 nanofibrous membranes yielding to composite materials M1 and M2. FE-SEM analysis confirmed the presence of particles incorporated on the nylon nanofibers. The release of the entrapped molecules (garlic extract) from the P1, P2, M1, and M2 materials was evaluated using cyclic voltammetry measurements. Electrochemical studies showed that at acidic pH P1 and M1 were unable to release their entrapped cargo (closed gate), whereas at neutral pH both materials release their loading (open gate). Dealing with P2 and M2 materials, in the absence of pancreatin a negligible release is observed (closed gate), whereas in the presence of enzyme the load is freely to diffuse to the solution. These newly developed composite nanomaterials, provide a homogeneous easy-to-handle system with controlled delivery and bioactive-protective features, having potential applications on pharmacology, medical and engineering fields.