Open AccessPhotoresponsive miR-34a/Nanoshell Conjugates Enable Light-Triggered Gene Regulation to Impair the Function of Triple-Negative Breast Cancer Cells
Author(s) -
Megan N. Dang,
Carolina Casas,
Emily S. Day
Publication year - 2020
Publication title -
nano letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.853
H-Index - 488
eISSN - 1530-6992
pISSN - 1530-6984
DOI - 10.1021/acs.nanolett.0c03152
Subject(s) - triple negative breast cancer , cancer research , nanocarriers , transfection , breast cancer , nanoshell , microrna , chemistry , microbiology and biotechnology , biophysics , cancer , medicine , nanotechnology , materials science , biology , gene , drug delivery , nanoparticle , biochemistry
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.