Development of gold nanoparticle-based theranostic agents for molecular imaging and cancer therapy
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This research explored the use of Au nanoparticles on molecular imaging and cancer theranostics, with focuses on the fabrication of new materials, the incorporation of new medical isotope, as well as new labeling and detecting techniques. The first part focuses on the synthesis and characterization of PdCu@Au core-shell tripods and their application in cancer theranostics. Innovative radiolabeling technique was developed to incorporate Cu-64 into the crystal lattice of the PdCu@Au tripods for improved radiolabeling stability. Novel biomarker of C-C chemokine receptor type 5 was selected to target triple negative breast cancer. With characteristic localized surface plasmon resonance in the near infrared range, positron emission tomography guided photothermal therapy was also demonstrated. In addition, the PdCu@Au tripods demonstrated a much brighter two-photon luminescence than that from Au nanorods, with a 3.6 ± 0.9 times larger two-photon action cross section and comparable quantum yield. The second part focuses on the use of Au-199 as a new medical isotope for the improvement of imaging quality of single-photon emission computed tomography. With Au-199 incorporated into the crystal lattice of nanoparticles improved radiolabeling stability was demonstrated. The third part demonstrated the use of Arg-Gly-Asp peptide-conjugated Au nanorods for radio-sensitization in radio therapy. This radio-sensitization effect was proofed to be the result of decreased expression level of αvβ3 integrin and increased G2/M arresting in cell cycle. Future directions on the improvement of biocompatibility of nanoparticle based theranostic agents were also outlined.