Due to their unique properties, engineered nanoparticles (NPs) have found broad use in industry, technology, and medicine, including as a vehicle for drug delivery. However, the understanding of NPs' interaction with different types of mammalian cells lags significantly behind their increasing adoption in drug delivery. In this study, we show unique responses of human epithelial breast cells when exposed to polymeric Eudragit® RS NPs (ENPs) for 1-3 days. Cells displayed dose-dependent increases in metabolic activity and growth, but lower proliferation rates, than control cells, as evidenced in tetrazolium salt (WST-1) and 5-bromo-2'-deoxyuridine (BrdU) assays, respectively. Those effects did not affect cell death or mitochondrial fragmentation. We attribute the increase in metabolic activity and growth of cells culture with ENPs to three factors: (1) high affinity of proteins present in the serum for ENPs, (2) adhesion of ENPs to cells, and (3) activation of proliferation and growth pathways. The proteins and genes responsible for stimulating cell adhesion and growth were identified by mass spectrometry and Microarray analyses. We demonstrate a novel property of ENPs, which act to increase cell metabolic activity and growth and organize epithelial cells in the epithelium as determined by Microarray analysis.