Researcher(s)
- Nikos Demetriou, Biomedical Engineering, University of Delaware
Faculty Mentor(s)
- Emily Day, Biomedical Engineering, University of Delaware
Abstract
Nikos Demetriou
Abstract
Triple-Negative breast cancer (TNBC), an aggressive breast cancer subtype, accounts for approximately 20% of all breast cancer cases and leads to poor outcomes for patients. Unlike other subtypes of breast cancer, TNBC lacks all breast cancer associated receptors, which makes it difficult to treat since most current treatment options focus on targeting these receptors. As a result, there are a lack of therapeutic options used to treat TNBC and it is critical to develop novel techniques to better target TNBC. One of the causes of TNBC progression is due to the up-regulation of the Wnt signaling pathway. In TNBC, there is an abundant production of Wnt ligands which allows for increased binding to Frizzled7 (FZD7) transmembrane receptors present on cells. This increased binding allows for the activation of downstream genes that promote cell proliferation, migration, and invasion of cancer cells. In the past, methods have been employed to prevent this ligand binding through the use of Wnt signaling inhibition. One effective method is through the use of FZD7 antibody linker conjugated nanoshell (NS) systems that can effectively bind to the FZD7 receptor to induce Wnt ligand binding inhibition. Preliminary data has shown that using a lower antibody loading density allows for improved therapeutic efficacy compared to the high loading condition using in vitro cell culture models. In this project, we investigate how antibody loading density on the surface of gold nanoshells affects cellular uptake to inhibit TNBC. We coated nanoshells with two concentrations of antibody loading densities and a fluorescent dye which we then characterized signal across groups. We treated TNBC cells with the fluorescent conjugated nanoshells and assessed cellular uptake via flow cytometry. Our findings suggest that antibody loading density may affect cellular uptake of TNBC cells and could be a factor contributing to therapeutic efficacy.