Triple-negative breast cancer targeting and killing by EpCAM-directed, plasmonically active nanodrug systems
Menée notamment sur des lignées cellulaires de cancer du sein triplement négatif et à l'aide de modèles murins, cette étude met en évidence l'intérêt d'un système de nanobâtonnets d'or recouverts d'argent et conjugués à un anticorps ciblant la molécule d'adhésion EpCAM pour détecter, à l'aide de techniques d'imagerie (spectroscopie Raman, microscopie photoacoustique), des cellules tumorales exprimant EpCAM et leur délivrer efficacement des agents anticancéreux
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.