Photoresponsive miR-34a/Nanoshell Conjugates Enable Light-Triggered Gene Regulation to Impair the Function of Triple-Negative Breast Cancer Cells.

Abstract

Triple-negative breast cancer (TNBC) is an aggressive disease that requires new interventions. A promising approach to improve patient prognosis 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. Nanocarriers designed to increase miR-34a stability and cellular entry have lacked specificity and potency. To overcome these limitations, we conjugated miR-34a to photoresponsive gold nanoshells (NS), which can release tethered miR-34a upon excitation with continuous wave (CW) or nanosecond (ns) pulsed near-infrared light to facilitate on-demand gene regulation. We demonstrate that miR-34a/NS can regulate downstream miR-34a targets following irradiation to reduce TNBC cell viability, proliferation, and migration. Further, we show ns pulsed light releases miRNA more effectively than CW light, and that released miR-34a is as potent as transfected miR-34a. These findings signify miR-34a/NS as promising tools for precisely controlled gene regulation of TNBC.