Nanoparticles have been studied for drug delivery with enormous potential to reduce toxicity or side effects of drugs. Although these systems are usually reported as safe, there are few studies testing the possible cytotoxic effects of nanoparticles. For this study, we developed nanospheres (NS) using poly (ɛ-caprolactone) and evaluated its effects in the tumor (HEp-2) and non-tumor (MRC5) cells. We also assessed the effects of a polyphenols-rich extract (PE) and its association to the formulation of the NS. To address the mechanisms of action of NS, cell viability, oxidative stress parameters and morphological changes were evaluated in the tumor and non-tumor cells. We observed that the pH of NS in presence or absence of PE was stable between a range of 6.0; diameter was around 200 nm and both samples exhibited narrow distribution (polydispersity index up to 0.19) with zeta potential from -9.6 to -10.6 mV. Low association rate for NS plus PE (efficiency of 19.05 %)was found; therefore, further studies and formulations are needed to improve PE encapsulation. NS reduced viability with different levels of toxicity (IC50 values460 ± 25 µg.mL-1for HEp-2 and 573 ± 51 µg.mL-1 for MRC5 cells; p=0.008,t-test).This reduction was associated with alterations in redox metabolism. Changes in symmetry and cell adherence at highest doses were observed in both cells. Results suggest that, depending on the applied concentrations and the cell type, NS may interfere with the cellular response.