Design and Characterization of Multimeric RGD Peptidomimetics Conjugated Gold Nanoparticles for Tumor Diagnostic and Enhanced X-ray Radiotherapy
Student: James Teh
Advisor: Robert Hanson
Gold nanoparticles (AuNPs) have unique physical and chemical properties appropriate for diagnostic and therapeutic applications in cancer. A novel approach is the use of AuNPs for radiotherapy, which upon exposure to low-energy X-ray radiation produces Auger electrons ultimately causing cellular apoptosis. Thus, a radio-sensitization effect of AuNPs can be achieved by making them more selective towards the target tumor cells. AuNPs can be engineered to conjugate with targeting ligands designed to bind specifically to receptors on tumor cell for molecular-specific imaging and detection. Over-expression of αvβ3 integrin receptors on the surface of tumor cells plays a critical role in regulating tumor invasion and metastasis. Therefore, targeting ligands containing the RGD sequence have been developed to have high specific binding affinity toward αvβ3 integrin receptors. Monovalent ligands may interact too weakly for adequate tumor targeting, and therefore we proposed a new approach in which AuNPs that display multivalent ligands may overcome this problem. Thus, the goal of this proposal is to functionalize the surface of AuNPs with linkers that incorporate multivalency. RGD peptidomimetics will be designed for coupling via “click” chemistry to trivalent dendrons which are themselves designed to bind to AuNPs. Furthermore, surface-enhanced Raman scattering (SERS) tags are covalently bound to the surface of AuNPs to produce significant Raman signals that will be employed for bioimaging. Investigations conducted on this approach will be employed in vitro and in vivo using human cancer cells expressing αvβ3 integrin receptors.