Preliminary Study On The Interactions Of Gold Nanoparticles With Different Subtype Breast Cancer Cells

Due to their inertness, biocompatibility and special optical properties, gold nanoparticles have gained intensive attentions and tremendous works have reported their potential in diagnosis and treatment of cancer. However, their safety for biomedical applications is still controversial. A full understanding of the interactions of gold nanoparticles with cells is necessary in order to evaluate their safety. Unfortunately, knowledge on gold-cell interactions is still incomplete. Besides, the interplay between gold nanoparticles and different subtype of breast cancer cells is rare. In the present study, a 15 nm gold nanoparticle, modified with 11-mercaptoundecanoic acid(MUA), was synthesized (AuNP@MUA). The interactions of AuNP@MUA with ER+(MCF-7)/ER-(MDA-MB-231) breast cancer cells, including cytotoxicity, cellular uptake, intracellular localiazation and exocytosis, were carefully investigated. Cytotoxicity of AuNP@MUA was evaluated by analyzing its effects on viability, cytoskeleton structure, reactive oxygen species (ROS) and mitochondrial membrane potential (MMP) of cells. Our results show that AuNP@MUA are nontoxic to MCF-7 and MDA-MB-231 at concentrations of 600 pM or lower. Higher nanoparticle concentrations (1200 pM) induce toxicity to MCF-7 but not MDA-MB-231. Confocal laser scanning microscopy was employed to study cellular uptake of AuNP@MUA by two-photon induced luminescence. The data show that MCF-7 and MDA-MB-231 cells internalize AuNP@MUA in a concentration- and time-dependent manner, and MCF-7 is far more effective in taking up AuNP@MUA. Furthermore, serum proteins may influence cellular uptake of AuNP@MUA by adsorption to the surface of gold nanoparticles. Intracellular localization of AuNP@MUA was analyzed by TEM and they were only observed in vesicular structures, such as endosomes or lysosomes of MCF-7 and MDA-MB-231. After their internalization and trafficking into endosomes or lysomes, AuNP@MUA were eliminated by MCF-7 and MDA-MB-231 in similar trends by exocytosis. These data suggest different subtype of tumor cells should be considered to fully understand gold-cell interactions.