Protease-activated nanoshell therapy
Morton, Jennifer Garner
West, Jennifer L.
Master of Science
This thesis describes the development of photothermal nanoshell therapy activated by proteases. Hirsch et al. previously showed that the optical spectrum of crosslinked nanoshells within the UV-visible range reveals a broader, red-shifted, and lower peak absorbance as compared to disperse nanoshells. As described in this thesis, studies showed this decrease in absorbance corresponds with a lower temperature change upon laser irradiation of the nanoshells. Near infrared (NIR)-absorbing silica-gold nanoshells were crosslinked with a proteolytically degradable linker, resulting in a broadening, red-shifting, and decrease of the peak absorbance. After collagenase was added to the crosslinked nanoshells, the peak absorbance increased, suggesting degradation of the linker and subsequent dispersion of the nanoshells. The results described here suggest that this may be applied to protease-activation in vivo within the tumor in an effort to increase tumor specificity and to protect surrounding normal tissue.