An ongoing need for new cancer therapeutics exists, especially ones that specifically home and target triple negative breast cancer (TNBC) tumors. Because TNBC does not express 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 targeting EpCAM and loaded with doxorubicin. This novel nanodrug system, EpCAM-AuNR/Ag/Dox, was found to specifically target EpCAM-expressing tumor cells compared to low EpCAM-expressing tumors. Namely, the system had an inhibiting cell viability effective dose (ED50) of 3μM on 4T1 cells and an ED50 of 110μM for MDA-MD-231 cells. Flow cytometry 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 its thin silver coating, the AuNR/Ag allowed for detection by surface-enhanced Raman spectroscopy (SERS) and photoacoustics (PA). Analysis by both imaging detection techniques 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). In conclusion, our novel approach establishes a plasmonically-active nanodrug therapeutic system for TNBC and, potentially, a delivery system with improved multimodal imaging capability for other clinically approved chemotherapeutics with dose-limiting toxicities, such as platinum-based or taxane-based therapies.
Citation Format: Samir V. Jenkins, Zeid A. Nima, Kieng B. Vang, Dmitry Nedosekin, Vladimir P. Zharov, Robert J. Griffin, Alexandru S. Biris, Ruud P. Dings. Breast cancer targeting by theranostic gold nanorods [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr LB-312. doi:10.1158/1538-7445.AM2017-LB-312