Gold Nanorods Indirectly Promote Migration of Metastatic Human Breast Cancer Cells in Three-Dimensional Cultures

Gold nanomaterials are intensively studied for applications in disease detection, diagnosis and therapeutics, and this has motivated considerable research to determine their interaction with biomolecules, cells and cell behaviors. However, few studies look at how nanomaterials alter the extracellular matrix (ECM) and cell–ECM interactions. Nanomaterials in the body would interact with the entire cellular environment, and it is imperative to account for this when studying the impact of nanomaterials on living systems. Furthermore, recent evidence finds that migration rates of cells in 2D can be affected by nanomaterials, and uptake of the nanomaterials is not necessary to exert an effect. In this study, three-dimensional nested type I collagen matrices were utilized as a model ECM to study how gold nanorods affect the migration of MDA-MB-231 human breast cancer cells. Spontaneous cell migration through collagen containing gold nanorods was found to increase with increasing concentrations of gold nanorods, independent of intracellular uptake of the nanorods. Gold nanorods in the collagen matrix were found to alter collagen mechanical properties and structure, molecular diffusion, cellular adhesion, cell morphology, mode of migration and protease expression. Correlation between decreased cellular adhesion and rounded cell morphology and locomotion in nanorod-containing collagen suggests the induction of an amoeboid-like migratory phenotype.