Photothermal therapies using near infrared absorbing nanoparticles

This thesis describes the development of new infrared (NIR) absorbing nanoparticles for use in biomedical therapeutic applications. Gold nanoshells with a dielectric core of silica developed at Rice University have shown tunable optical properties, these and nanoshells with a gold sulfide core are exploited in this thesis to develop several therapeutic applications. These applications include bonding of tissues, integrated imaging and therapy for cancer applications and targeted destruction of cancer tumor cells to improve on the efficacy of photothermal therapy using nanoshells. In addition, the development of nanoshells with a gold sulfide core and a gold shell are utilized for therapeutic application similarly to gold-silica nanoshells. These gold-gold sulfide nanoshells are attractive for use as a therapeutic agent because their size makes them more efficient at absorbing light energy and converting it to heat, allowing them to achieve higher temperatures faster than gold-silica nanoshells. In addition, the smaller size allows them to circulate longer in vivo and could allow them to be delivered more efficiently into tumors. The use of nanoshells to replace indocyanine green (ICG), an FDA approved exogenous chromophore, in tissue welding application shows great promise in vivo . Nanoshells were successfully targeted against prostate cancer cells by using antibodies against surface marker Prostate Specific Membrane Antigen (PSMA) anchored to the cell surface which are over-expressed in the more aggressive prostate malignancies. Additionally, nanoshells were targeted against the less aggressive prostate tumor line using EphrinA1, a ligand which binds to the Eph A2 receptor over-expressed on prostate tumor cells. Both of these approaches show excellent binding and destruction of cells in vitro . A single nanoshell was developed which have both scattering and absorbing properties and was shown to be effective at allowing imaging of tumors and subsequent destruction. These nanoshells provided a 56% improvement in imaging contrast and 82% survival in vivo . Finally, gold-gold sulfide nanoshells are developed and it is shown that they can achieve higher temperatures faster than gold-silica nanoshells at the same optical densities and laser energies. Tumor bearing treated with these nanoshells show complete tumor regression in vivo