Iron(III)-doped, silica : biodegradable, self-targeting nanoparticles

Silica nanoparticles are currently being investigated for a number of medical applications. Silica is FDA approved for oral consumption; however, its use in vivo has been questioned because of its potential for bioaccumulation. In an attempt to remedy this problem, silica nanoshells have been made biodegradable by doping iron(III) into the nanoshells. Small molecule chelation and serum studies were performed to determine if the removal of iron(III) from the nanoshell structure would facilitate nanoshell degradation. It was determined that iron chelators such as EDTA, desferrioxamine, and Deferiprone cause the nanoshells to degrade upon removal of iron, as evidenced by UV-vis absorption spectral studies and SEM experiments. The submersion of Fe(III)-doped, silica nanoshells in fetal bovine serum and human serum also appear to degrade due to the removal or iron by serum proteins, which is easily seen in SEM images. In addition to biodegradability, being able to modify nanoparticles with targeting ligands is highly desirable for targeted drug delivery applications. This is often accomplished by the conjugation of a targeting moiety (protein, apatmer, polymer, etc.) to the surface of the nanoparticle. Conjugation of such compounds, however, can be difficult and complicate other desired surface chemical modification reactions. This issue is remedied by the incorporation of iron(III) into silica nanoshells. Iron(III) in the nanoshells can be bound by transferrin, a serum protein, and subsequently transported into a cell via a transferrin receptor-mediated endocytosis pathway. The uptake of Fe(III)-doped, silica nanoshells via a transferrin receptor-mediated pathways was observed with the use of fluorescence and confocal microscopy and also using fluorescence assisted cell sorting. Based on the results of these studies, it can be concluded that the doping of iron(III) into silica nanoshells results in a self- targeting nanoparticle (a nanoparticle that does not require the covalent conjugation of a targeting moiety to its surface

Self-assembled Targeting of Cancer Cells by Iron(III)-doped, Silica Nanoparticles.

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

Self-assembled Targeting of Cancer Cells by Iron(III)-doped, Silica Nanoparticles.

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

Mechanically Tunable Hollow Silica Ultrathin Nanoshells for Ultrasound Contrast Agents

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