2C: Photoresponsive miR-34a/Nanoshell Conjugates Enable Light-Triggered Gene Regulation to Impair the Function of Triple-Negative Breast Cancer Cells, Megan Dang

Triple-negative breast cancer (TNBC) is an aggressive disease that requires new interventions. A promising therapy is to introduce tumor suppressive miR-34a into TNBC cells. Unfortunately, naked miR-34a is not effective therapeutically because it is degraded by nucleases and cannot passively enter cells. Additionally non-specific delivery of miRNA can inherently cause widespread gene regulation. Nanocarriers designed to increase miR-34a stability and cellular entry have not fully addressed the lack of specificity and potency. To overcome these limitations, we conjugated miR-34a to photoresponsive gold nanoshells (NS) to be released upon excitation with continuous wave (CW) or nanosecond (ns) pulsed near-infrared light for on-demand gene regulation. We show ns pulsed light releases miRNA more effectively than CW light and that intracellularly ns pulsed light delivers more released miRNA to the nucleus. As a result, the released miR-34a/NS can regulate downstream gene targets following irradiation to reduce TNBC cell viability, proliferation, and migration more effectively. These findings signify miR-34a/NS as promising tools for controlled gene regulation of TNBC.