DOX-loaded silver nanotriangles and photothermal therapy exert a synergistic antibreast cancer effect via ROS/ERK1/2 signaling pathway

The combination of multiple therapies has been proved to be more effective than a single therapy for many cancers. This study aimed to investigate the synergistic antibreast cancer effect of doxorubicin-loaded silver nanotriangles (DOX-AgNTs) combined with near-infrared (NIR) irradiation and explore the underlying mechanism. AgNTs were prepared by a chemical method and DOX was loaded via electrostatic adsorption. Characterization was performed by transmission electron microscopy, ultraviolet-visible spectroscopy and dynamic light scattering. The viability of MDA-MB-231 cells was detected by using MTT assay to evaluate the synergistic anticancer effect of DOX-AgNTs combined with NIR irradiation. The intracellular reactive oxygen species (ROS) level and cell apoptosis were analyzed by flow cytometry. Mitochondrial membrane potential (MMP) was measured with fluorescence microscopy. The mechanism was further investigated with ROS scavenger N-acetylcysteine and specific inhibitors of extracellular signal-regulated kinase 1/2 (ERK1/2), C-jun N-terminal kinase and p38 pathways. Characterization results revealed that the prepared AgNTs were mostly triangular and the mean edge length was about 126 nm. The combination of DOX-AgNTs and NIR exhibited a superior synergistic anticancer effect over single DOX-AgNTs or photothermal therapy (PTT). N-acetylcysteine and ERK1/2 inhibitor U0126 were found to significantly rescue the decreased cell viability, declined MMP and increased apoptosis induced by the combined treatment. Our results suggested that DOX-AgNTs combined with PTT performed a synergistic antibreast cancer effect. The synergy might be closely associated with the excessive production of ROS, changed MMP and the activation of ERK1/2 signaling pathway. These findings might provide a new perspective for the development of breast cancer treatments with excellent efficacy.