Online

Vrolijk, Michael Aaron

Chemistry

2017

M.S.

DNA and interfering RNA (RNAi) -- short interfering RNA (siRNA) and micro RNA (miRNA) -- are promising new cancer therapies, especially for drug resistant lines. However, they require a delivery system in vivo to prevent degradation and off target effects. Silica based nanoparticles, both solid and mesoporous, are a promising option due to their biocompatibility, ease of preparation and morphology control, reproducibility, and facile addition of functional groups including targeting ligands. After a brief introduction to cancer treatment and review of the current nanoparticle treatments undergoing clinical trials, this thesis details the many methods explored over the past ten years to fine-tune particle preparation, pore size, functionalization, and delivery strategies. The majority of both solid and mesoporous silica nanoparticles are synthesized using the sol-gel method and then various functionalization techniques are employed to load and protect the oligonucleotides. Externally loaded systems generally use a combination of polyethylenimine (PEI) and polyethylene glycol (PEG). Mesoporous silica nanoparticles internally load the DNA or RNAi, resulting in the added variable of pore size. Several groups have investigated how pore size alters loading and release kinetics to perfect this variable. Many groups have also tested ligands targeting for over expressed proteins on the intended cancer, triggered release techniques, cell-penetrating peptides in order to create a viable in vivo delivery system. By compiling the techniques employed by researchers over the past ten years, this thesis will elucidate which approaches are most promising for future research. Furthermore, overall strategies within the field are suggested to more easily compare studies and evaluate methods.