An ongoing need for new
cancer therapeutics exists, especially ones that specifically home and target
triple-negative breast cancer. Because
triple-negative breast cancer express low or are devoid of
estrogen,
progesterone, or Her2/Neu receptors, another target must be used for advanced drug delivery strategies. Here, we engineered a nanodrug delivery system consisting of
silver-coated
gold nanorods (AuNR/Ag) targeting epithelial cell adhesion/activating molecule (
EpCAM) and loaded with
doxorubicin. This nanodrug system, AuNR/Ag/Dox-
EpCAM, was found to specifically target
EpCAM-expressing
tumors compared to low
EpCAM-expressing
tumors. Namely, the nanodrug had an effective dose (ED50) of 3 μM in inhibiting 4T1 cell viability and an ED50 of 110 μM for MDA-MD-231 cells. Flow cytometry data indicated that 4T1 cells, on average, express two orders of magnitude more
EpCAM than MDA-MD-231 cells, which correlates with our ED50 findings. Moreover, due to the
silver coating, the AuNR/Ag can be detected simultaneously by surface-enhanced Raman spectroscopy and photoacoustic microscopy. Analysis by these imaging detection techniques as well as by inductively coupled plasma mass spectrometry showed that the targeted nanodrug system was taken up by
EpCAM-expressing cells and
tumors at significantly higher rates than untargeted nanoparticles (p < 0.05). Thus, this approach establishes a plasmonically active nanodrug
theranostic for
triple-negative breast cancer and, potentially, a delivery platform with improved multimodal imaging capability for other clinically relevant chemotherapeutics with dose-limiting toxicities, such as
platinum-based or
taxane-based
therapies.