A simple one-step procedure is described for the synthesis of spherical mesoporous silica, in which the size of the particles is controlled over a range of diameters from 65 to 740 nm by varying the initial silicate/surfactant concentration under dilute conditions. The particles were characterized using X-ray diffraction, transmission electron microscopy, and liquid nitrogen adsorption. Synthesis using a charged template, cetyltrimethylammonium bromide, under aqueous conditions yielded particles of irregular spherical shape with highly ordered mesoporous channels. Synthesis under ethanol/water cosolvent conditions yielded smooth spheres with a starburst mesopore structure extending from the center of the particle to the circumference. All materials were thermally stable and exhibited two steps in their liquid nitrogen isotherms corresponding to reversible channel filling and non-reversible adsorption between particles. Mesopore volumes varied from 0.64 to 0.93 cm 3 g -1 and surface areas varied from 917 to 1373 m 2 g -1 . From analysis of mesopore geometry and overall particle shape a three-stage mechanism for synthesis is proposed.
BackgroundNeuroblastoma is one of the most challenging malignancies of childhood, being associated with the highest death rate in paediatric oncology, underlining the need for novel therapeutic approaches. Typically, patients with high risk disease undergo an initial remission in response to treatment, followed by disease recurrence that has become refractory to further treatment. Here, we demonstrate the first silica nanoparticle-based targeted delivery of a tumor suppressive, pro-apoptotic microRNA, miR-34a, to neuroblastoma tumors in a murine orthotopic xenograft model. These tumors express high levels of the cell surface antigen disialoganglioside GD2 (GD2), providing a target for tumor-specific delivery.Principal FindingsNanoparticles encapsulating miR-34a and conjugated to a GD2 antibody facilitated tumor-specific delivery following systemic administration into tumor bearing mice, resulted in significantly decreased tumor growth, increased apoptosis and a reduction in vascularisation. We further demonstrate a novel, multi-step molecular mechanism by which miR-34a leads to increased levels of the tissue inhibitor metallopeptidase 2 precursor (TIMP2) protein, accounting for the highly reduced vascularisation noted in miR-34a-treated tumors.SignificanceThese novel findings highlight the potential of anti-GD2-nanoparticle-mediated targeted delivery of miR-34a for both the treatment of GD2-expressing tumors, and as a basic discovery tool for elucidating biological effects of novel miRNAs on tumor growth.
This paper reports on the enhancement of fluorescence that can result from the proximity of fluorophores to metallic nanoparticles (NPs). This plasmonic enhancement, which is a result of the localized surface plasmon resonance at the metal surface, can be exploited to improve the signal obtained from optical biochips and thereby lower the limits of detection. There are two distinct enhancement effects: an increase in the excitation of the fluorophore and an increase in its quantum efficiency. This study focuses on the first of these effects where the maximum enhancement occurs when the NP plasmon resonance wavelength coincides with the fluorophore absorption band. In this case, the excitation enhancement is proportional to the square of the amplitude of the electric field. The scale of the enhancement depends on many parameters, such as NP size and shape, metal type, and NPfluorophore separation. A model system consisting of spherical gold/silver alloy NPs, surrounded by a silica spacer shell, to which is attached a fluorescent ruthenium dye, was chosen and the dependence of the fluorescence enhancement on NP diameter was investigated. Theoretical calculations, based on Mie theory, were carried out to predict the maximum possible enhancement factor for spherical NPs with a fixed composition and a range of diameters. Spherical NPs of the same composition were fabricated by chemical preparation techniques. The NPs were coated with a thin silica shell to overcome quenching effects and the dye was attached to the shell.
A synthesis procedure is described for making functionalized mesoporous silica macrostructures that can serve as self-supporting adsorbents for environmental remediation and other separations applications. The material, whose mesopores were functionalized with 3-mercaptopropyltrimethoxysilane ligands, can be made into spheres, irregular particles, and truncated cones having diameters from 1 to 15 mm through a one-step emulsion synthesis procedure. Other shapes such as pellets can be formed by molding the precursor gel. The macro-and mesomorphology of the materials were characterized by X-ray diffraction, transmission electron microscopy, scanning electron microscopy, and 29 Si MAS NMR. Physisorption properties were investigated using nitrogen adsorption measurements. The surface area of these materials determined via the BET method ranged from 864 to 1184 m 2 g -1 . The materials are extremely effective in the removal of mercury and silver ions from aqueous solutions. The amount of mercury adsorbed ranged from 0.24 to 1.26 mmol g -1 , depending on the degree of functionalization. Silver is less strongly adsorbed than mercury, with a maximum loading of 0.89 mmol g -1 . In binary adsorption of mercury and silver ion mixtures, the selectivity for mercury ranged from 1.39 to 2.24. The adsorption capacity of the functionalized materials for nitrogen is comparable to that of unfunctionalized materials.
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