Anticancer Properties of Gold Nanoparticles Conjugated to Estrogen Receptor Ligands

The use of gold nanoparticles as drug delivery systems has the potential to completely revamp current approaches to cancer therapeutic treatments. Most chemotherapy drugs in use cannot differentiate tumor tissue from normal cell tissue and freely diffuse throughout both cancerous and normal, healthy cells, causing harmful nonspecific side effects. Due to the leakiness of tumor vessels, macromolecules such as nanoparticles preferentially accumulate at tumor cell sites and therefore reduce side effects that occur from normal cell interactions. With the addition of targeting molecules and coupling with photothermal therapy, targeted AuNP treatment holds the potential to be a very effective, versatile, and low toxic therapeutic treatment.  Currently, it is believed that the targeted AuNP treatment is comprised of two active components: targeting and photothermal lysis. The targeting molecules deliver AuNP to the cancer cells and the AuNP binds through either a cytosollic or intracellular pathway and photothermal therapy is performed. Most believe that phothermal lysis is the main contributor to the death of the cancer cells. The aim of this project is to investigate whether there is another pathway through which the targeted AuNP is able to induce the death of cancer cells. 17-β-estradiol was selected as the targeting molecule for this experiment. Since 17- β -estradiol binding and recruitment of cofactors is necessary for growth of ER+ cancer cells, we will determine whether a ligand containing 17-β-estradiol conjugated to a AuNP will prevent recruitment of coactivators and subsequently initiate cell programmed death when bound to the ER.