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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)

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