Breast cancer is the most prevalent form of cancer in women. HSP90 inhibitors are an exciting class of drugs used to treat breast cancer, as well as other cancers such as multiple myeloma. When coupled with Herceptin, HSP90 inhibitors have been effective in decreasing the survival of Her2 positive breast cancer cells, Cullin-5 (Cul5) has been shown to be required for the activity of Tanespimycin and id expressed at low levels in breast cancer cells compared to patient matched controls. The observed low Cul5 expression may play a role in the decreased efficacy of Tanespimycin as a montherapy reported in clinical trials. We reason that increasing Cul5 expression will alleviate poor performance of Tanespimycin. We have developed a method to deliver Tanespimycin plus Cul5 DNA to cells by modifying the surface of gold nanoparticles (AuNPs). Using a modified one phase method with polyethylenimine (PEI) or glutathione (GSH) as the ligand, AuNPs were synthesized. PEI has been reported to be extensively used for surface capping of AuNPs because of its polycationic properties, which can promote cell entry and endosomal escape. The second aim is to utilize glutathione (GSH), a biocompatible capping ligand to attach our payload as it forms a more stable nanoparticle and most significantly afford size dimension control. In addition, GSH is less cytotoxic than PEI. GSH is an antioxidant found in cells and aids in cancer cell survival. By exploiting this need, we anticipate higher uptake of the AuNPs due to GSH being attached. Characterization of AuNPs was done via UV-vis spectrum, TEM, gel electrophoresis assay and 1H NMR. The results of the synthesis, characterization and cell viability studies will be presented. Overcoming reduced Cul5 expression in cancer cells will increase sensitivity to HSP90 inhibitors. Our studies have the potential to increase the efficacy of HSP90 inhibitors in a broad range of cancers.

PEI or GSH coated gold nanoparticles conjugated to cullin-5 DNA and heat shock protein 90 inhibitor, tanespimycin, for breast cancer therapy

255th National Meeting (2018)

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