UC San Diego

Two materials in particular: porous silicon nanoparticles and iron oxide nanoparticles have already produced technologies geared towards the treatment of disease. The objective of this thesis is to harness the combined properties of porous silicon and iron oxide nanoparticles and investigate the suitability of this nanocomposite as T2 tunable materials for magnetic resonance imaging guided drug delivery. In the first two chapters, the tools and methodologies necessary for the development and study of porous silicon iron oxide nanocomposite based IGDD (image guided drug delivery) agents are identified and described. The optimization of transverse relaxation rate is crucial to building agents for magnetic resonance imaging. In this regard, in Chapter 3 the effects of the structural properties of iron oxide aggregates on transverse relaxation were studied. The transverse relaxation of several shapes of iron oxide nanoparticle clusters were analysed through monte carlo simulations. A shape described by a combination of circular and linear clusters was found to produce optimal transverse relaxation. Then, in Chapter 4 we investigate another mechanism to increase transverse relaxation. Here, the effect of tuning self diffusion coefficient of protons on transverse relaxation is studied by confining iron oxide aggregates into porous silicon matrices of two different pore sizes. Iron oxide nanoparticles loaded into 15nm porous silicon increased R2 to a greater extent than iron oxide nanoparticles loaded into a 25nm porous silicon matrix. In Chapter 5, the utility of the above mentioned porous silicon iron oxide nanocomposites as image guided drug delivery agents is studied. Nanoparticle formulations with an imaging and a therapeutic agent could allow non invasive assessment of low molecular weight drugs releasing from nanoparticles. In this regard, release of a hydrophobic drug and a hydrophilic drug from biodegradable porous silicon iron oxide nanocomposites were studied invitro. Quantification of drug release, self-diffusion coefficient of protons during degradation of the matrix and transverse relaxation times during 0-8 hours revealed the change in self- diffusion coefficient during degradation of the matrix as the mechanism for tuning transverse relaxation of porous silicon iron oxide nanocomposites. A linear relationship was observed for hydrophobic drugs between the percentage change in transverse relaxation and percentage drug released and a non linear relationship for hydrophilic drugs. Therefore, porous silicon iron oxide nanocomposites can be used to determine concentration of drug released from transverse relaxation measurements for hydrophobic drugs