Iron(III)-doped silica nanoshells are shown to possess an in vitro cell-receptor mediated targeting functionality for endocytosis. Compared to plain silica nanoparticles, iron enriched ones are shown to be target-specific, a property that makes them potentially better vehicles for applications, such as drug delivery and tumor imaging, by making them more selective and thereby reducing the nanoparticle dose. Iron(III) in the nanoshells can interact with endogenous transferrin, a serum protein found in mammalian cell culture media, which subsequently promotes transport of the nanoshells into cells by the transferrin receptor-mediated endocytosis pathway. The enhanced uptake of the iron(III)-doped nanoshells relative to undoped silica nanoshells by a transferrin receptor-mediated pathway was established using fluorescence and confocal microscopy in an epithelial breast cancer cell line. This process was also confirmed using fluorescence activated cell sorting (FACS) measurements that show competitive blocking of nanoparticle uptake by added holo-transferrin.

Perfluoropentane (PFP) gas filled biodegradable iron-doped silica nanoshells have been demonstrated as long-lived ultrasound contrast agents. Nanoshells are synthesized by a sol-gel process with tetramethyl orthosilicate (TMOS) and iron ethoxide. Substituting a fraction of the TMOS with R-substituted trialkoxysilanes produces ultrathin nanoshells with varying shell thicknesses and morphologies composed of fused nanoflakes. The ultrathin nanoshells had continuous ultrasound Doppler imaging lifetimes exceeding 3 hours, were twice as bright using contrast specific imaging, and had decreased pressure thresholds compared to control nanoshells synthesized with just TMOS. Transmission electron microscopy (TEM) showed that the R-group substituted trialkoxysilanes could reduce the mechanically critical nanoshell layer to 1.4 nm. These ultrathin nanoshells have the mechanical behavior of weakly linked nanoflakes but the chemical stability of silica. The synthesis can be adapted for general fabrication of three-dimensional nanostructures composed of nanoflakes, which have thicknesses from 1.4-3.8 nm and diameters from 2-23 nm.

© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. Perfluoropentane (PFP) gas-filled biodegradable iron-doped silica nanoshells have been demonstrated as long-lived ultrasound contrast agents. Nanoshells are synthesized by a sol-gel process with tetramethyl orthosilicate (TMOS) and iron ethoxide. Substituting a fraction of the TMOS with R-substituted-trialkoxysilanes produces ultrathin nanoshells with varying shell thicknesses and morphologies composed of fused nanoflakes. The ultrathin nanoshells have continuous ultrasound Doppler imaging lifetimes exceeding 3 h, are twice as bright using contrast-specific imaging, and have decreased pressure thresholds compared to control nanoshells synthesized with just TMOS. Transmission electron microscopy shows that the R-group-substituted trialkoxysilanes can reduce the mechanically critical nanoshell layer to 1.4 nm. These ultrathin nanoshells have the mechanical behavior of weakly linked nanoflakes but the chemical stability of silica. The synthesis can be adapted for general fabrication of 3D nanostructures composed of nanoflakes, which have thicknesses from 1.4 to 3.8 nm and diameters from 2 to 23 nm.