Gold Nanoparticles as a Drug Delivery Vehicle System Against ErbB2+ Breast Cancer

Abstract

Breast cancer is the most common and second leading cause of cancer related death among women. Currently, chemotherapy treatments involving heat shock protein 90 (Hsp90) inhibitors (17‐AAG) are not FDA approved due to their lack of clinical efficacy. Hsp90 inhibitors decrease binding and stabilization of clients that aid in tumor formation and growth. ErbB2, a Hsp90 client, is overexpressed in ErbB2+ breast cancers and promotes tumor progression. Cul5 is downregulated in ErbB2+ breast cancer cells making them resistant to chemotherapy treatments involving Hsp90 inhibitors. Cul5 is required for degradation of ErbB2 in response to Hsp90 inhibitors. Hsp90 inhibitors are not efficacious alone and require Cul5 for effective antitumor response. I have synthesized gold nanoparticles coated with anti‐ErbB2 antibody, 17‐AAG, and Cul5 DNA as an intracellular drug delivery mechanism. This targeted drug delivery vehicle has been evaluated in a cell culture model of drug resistance. We have constructed a breast cancer cell line in the past that is resistant to the HSP90 inhibitor 17‐AAG and we used this model system to evaluate Cul5 expression. Our hypothesis is that gold nanoparticles coated with Cul5 DNA, 17‐AAG, and anti‐ErbB2 antibodies will increase the sensitivity and specificity of Cul5 deficient ErbB2+ breast cancer cells to 17‐AAG. This has been achieved through comparing payload efficacy of differently sized gold nanoparticles and evaluating targeting of anti‐ErbB2 antibodies to ErbB2+ breast cancer cells. Specifically targeting and making breast cancer cells susceptible to Hsp90 inhibitors will be a milestone in improving therapeutic treatment for those diagnosed.