Mesoporous organic-inorganic hybrid materials, a new class of materials characterized by large specific surface areas and pore sizes between 2 and 15 nm, have been obtained through the coupling of inorganic and organic components by template synthesis. The incorporation of functionalities can be achieved in three ways: by subsequent attachment of organic components onto a pure silica matrix (grafting), by simultaneous reaction of condensable inorganic silica species and silylated organic compounds (co-condensation, one-pot synthesis), and by the use of bissilylated organic precursors that lead to periodic mesoporous organosilicas (PMOs). This Review gives an overview of the preparation, properties, and potential applications of these materials in the areas of catalysis, sorption, chromatography, and the construction of systems for controlled release of active compounds, as well as molecular switches, with the main focus being on PMOs.

Silica-based mesoporous organic-inorganic hybrid materials.

Small synthetic molecules called growth hormone secretagogues (GHSs) stimulate the release of growth hormone (GH) from the pituitary. They act through the GHS-R, a G protein-coupled receptor whose ligand has only been discovered recently. Using a reverse pharmacology paradigm with a stable cell line expressing GHS-R, we purified an endogenous ligand for GHS-R from rat stomach and named it "ghrelin," after a word root ("ghre") in Proto-Indo-European languages meaning "grow." Ghrelin is a peptide hormone in which the third amino acid, usually a serine but in some species a threonine, is modified by a fatty acid; this modification is essential for ghrelin's activity. The discovery of ghrelin indicates that the release of GH from the pituitary might be regulated not only by hypothalamic GH-releasing hormone, but also by ghrelin derived from the stomach. In addition, ghrelin stimulates appetite by acting on the hypothalamic arcuate nucleus, a region known to control food intake. Ghrelin is orexigenic; it is secreted from the stomach and circulates in the bloodstream under fasting conditions, indicating that it transmits a hunger signal from the periphery to the central nervous system. Taking into account all these activities, ghrelin plays important roles for maintaining GH release and energy homeostasis in vertebrates.

https://www.physiology.org/doi/pdf/10.1152/physrev.00012.2004

Ghrelin: Structure and Function

Mesoporous silica nanoparticles as controlled release drug delivery and gene transfection carriers

Nanomaterials, such as metal or semiconductor nanoparticles and nanorods, exhibit similar dimensions to those of biomolecules, such as proteins (enzymes, antigens, antibodies) or DNA. The integration of nanoparticles, which exhibit unique electronic, photonic, and catalytic properties, with biomaterials, which display unique recognition, catalytic, and inhibition properties, yields novel hybrid nanobiomaterials of synergetic properties and functions. This review describes recent advances in the synthesis of biomolecule-nanoparticle/nanorod hybrid systems and the application of such assemblies in the generation of 2D and 3D ordered structures in solutions and on surfaces. Particular emphasis is directed to the use of biomolecule-nanoparticle (metallic or semiconductive) assemblies for bioanalytical applications and for the fabrication of bioelectronic devices.

Integrated Nanoparticle–Biomolecule Hybrid Systems: Synthesis, Properties, and Applications

Research on mesoporous materials for biomedical purposes has experienced an outstanding increase during recent years. Since 2001, when MCM-41 was first proposed as drug-delivery system, silica-based materials, such as SBA-15 or MCM-48, and some metal-organic frameworks have been discussed as drug carriers and controlled-release systems. Mesoporous materials are intended for both systemic-delivery systems and implantable local-delivery devices. The latter application provides very promising possibilities in the field of bone-tissue repair because of the excellent behavior of these materials as bioceramics. This Minireview deals with the advances in this field by the control of the textural parameters, surface functionalization, and the synthesis of sophisticated stimuli-response systems.

Mesoporous materials for drug delivery.

NEUROTRANSMITTER released from neurons is known to signal to neighbouring neurons and glia1–3 Here we demonstrate an additional signalling pathway in which glutamate is released from astrocytes and causes an NMDA (N-methyl-d-aspartate) receptor-mediated increase in neuronal calcium. Internal calcium was elevated and glutamate release stimulated by application of the neuro-ligand bradykinin to cultured astrocytes. Elevation of astrocyte internal calcium was also sufficient to induce glutamate release. To determine whether this released glutamate signals to neurons, we studied astrocyte–neuron co-cultures. Bradykinin significantly increased calcium levels in neurons co-cultured with astrocytes, but not in solitary neurons. The glutamate receptor antagonists d-2-amino-5-phosphonopentanoic acid and d-glutamylglycine prevented bradykinin-induced neuronal calcium elevation. When single astrocytes were directly stimulated to increase internal calcium and release glutamate, calcium levels of adjacent neurons were increased; this increase could be blocked by d-glutamylglycine. Thus, astrocytes regulate neuronal calcium levels through the calcium-dependent release of glutamate.

Glutamate-mediated astrocyte-neuron signalling.

An MCM-41 type mesoporous silica nanosphere-based (MSN) controlled-release delivery system has been synthesized and characterized using surface-derivatized cadmium sulfide (CdS) nanocrystals as chemically removable caps to encapsulate several pharmaceutical drug molecules and neurotransmitters inside the organically functionalized MSN mesoporous framework. We studied the stimuli-responsive release profiles of vancomycin- and adenosine triphosphate (ATP)-loaded MSN delivery systems by using disulfide bond-reducing molecules, such as dithiothreitol (DTT) and mercaptoethanol (ME), as release triggers. The biocompatibility and delivery efficiency of the MSN system with neuroglial cells (astrocytes) in vitro were demonstrated. In contrast to many current delivery systems, the molecules of interest were encapsulated inside the porous framework of the MSN not by adsorption or sol−gel types of entrapment but by capping the openings of the mesoporous channels with size-defined CdS nanoparticles to physically block...

A mesoporous silica nanosphere-based carrier system with chemically removable CdS nanoparticle caps for stimuli-responsive controlled release of neurotransmitters and drug molecules.

We synthesized a MCM-41-type mesoporous silica nanosphere (MSN)-based gene transfection system, where second generation (G2) polyamidoamines (PAMAMs) were covalently attached to the surface of MSN The G2-PAMAM-capped MSN material (G2-MSN) was used to complex with a plasmid DNA (pEGFP-C1) that encodes for an enhanced green fluorescence protein The gene transfection efficacy, uptake mechanism, and biocompatibility of the G2-MSN system with various cell types, such as neural glia (astrocytes), human cervical cancer (HeLa), and Chinese hamster ovarian (CHO) cells, were investigated The mesoporous structure of the MSN material allows membrane-impermeable molecules, such as pharmaceutical drugs and fluorescent dyes, to be encapsulated inside the MSN channels The system renders the possibility to serve as a universal transmembrane carrier for intracellular drug delivery and imaging applications

A polyamidoamine dendrimer-capped mesoporous silica nanosphere-based gene transfection reagent.

ATP caused a dose-dependent, receptor-mediated increase in the release of glutamate and aspartate from cultured astrocytes. Using calcium imaging in combination HPLC we found that the increase in intracellular calcium coincided with an increase in glutamate and aspartate release. Competitive antagonists of P2 receptors blocked the response to ATP. The increase in intracellular calcium and release of glutamate evoked by ATP were not abolished in low Ca2+-EGTA saline, suggesting the involvement of intracellular calcium stores. Pre-treatment of glial cultures with an intracellular Ca2+ chelator abolished the stimulatory effects of ATP. Thapsigargin (1 µm), an inhibitor of Ca2+-ATPase from the Ca2+ pump of internal stores, significantly reduced the calcium transients and the release of aspartate and glutamate evoked by ATP. U73122 (10 µm), a phospholipase C inhibitor, attenuated the ATP-stimulatory effect on calcium transients and blocked ATP-evoked glutamate release in astrocytes. Replacement of extracellular sodium with choline failed to influence ATP-induced glutamate release. Furthermore, inhibition of the glutamate transporters p-chloromercuri-phenylsulfonic acid and ltrans-pyrolidine-2,4-dicarboxylate failed to impair the ability of ATP to stimulate glutamate release from astrocytes. However, an anion transport inhibitor, furosemide, and a potent Cl− channel blocker, 5-nitro-2(3-phenylpropylamino)-benzoate, reduced ATP-induced glutamate release. These results suggest that ATP stimulates excitatory amino acid release from astrocytes via a calcium-dependent anion-transport sensitive mechanism.

ATP stimulates calcium-dependent glutamate release from cultured astrocytes.

This article demonstrates that directional outgrowth of neurites is promoted by applying a combination of physical and chemical cues to biodegradable polymer substrates. Films of poly-D,L-lactic acid and poly(lactide-co-glycolide) were micropatterned to form grooves on substrate surfaces, using novel indirect transfer techniques developed specifically for biodegradable polymers that cannot be micropatterned directly. Laminin was selectively adsorbed in the grooves. Whole and dissociated dorsal root ganglia were seeded on the substrates and neurite outgrowth and alignment along the microgrooves were measured. The microgrooves provide physical guidance, whereas laminin provides chemical cues to the neurons. The groove depth and spacing were found to significantly influence neurite alignment. The presence of laminin was found to promote neurite adhesion and outgrowth along the grooves. Using a combination of optimized physical and chemical cues, excellent spatial control of directional neurite outgrowth, with up to 95% alignment of neurites, was obtained. The synergistic effect of physical and chemical guidance cues was found to be more effective than individual cues in promoting directional outgrowth of neurites.

https://lib.dr.iastate.edu/cgi/viewcontent.cgi?article=1171&context=cbe_pubs

Srdija Jeftinija

Papers

Glutamate-mediated astrocyte-neuron signalling.

A mesoporous silica nanosphere-based carrier system with chemically removable CdS nanoparticle caps for stimuli-responsive controlled release of neurotransmitters and drug molecules.

A polyamidoamine dendrimer-capped mesoporous silica nanosphere-based gene transfection reagent.

ATP stimulates calcium-dependent glutamate release from cultured astrocytes.

Synergistic Effects of Physical and Chemical Guidance Cues on Neurite Alignment and Outgrowth on Biodegradable Polymer Substrates