OBJECTIVE The aim of this study is to design, fabricate and determine the cytotoxic effects of dual loaded paclitaxel and 17-AAG in stealth polymeric nanoparticles. The nanoparticles were fabricated by dispersion polymerization. METHODS Two breast cancer cell lines (MCF-7 and SKBR-3) were cultured and treated with media only, blank nanoparticles, paclitaxel (as a free drug), 17-AAG (free drug), paclitaxel + 17-AAG combination (as free drugs), and paclitaxel + 17-AAG combination loaded in poly-ε-caprolactone stealth nanoparticles. Each drug in the combination was half the concentration of the single free drug. RESULTS The cytotoxic effects of the paclitaxel treatment and that of the combination (free drug) were found to be similar in both SKBR3 and MCF7 cell lines. Similar cytotoxic effects were observed for the drug combination both in the drug loaded nanoparticles formulation and in free drug form for both cell lines. CONCLUSIONS Both paclitaxel and 17-AAG were effectively loaded and released from the polymeric nanoparticles. Paclitaxel (free drug), paclitaxel-17AAG combination (free drug), and dual drug-loaded nanoparticles had similar cytotoxic effects on both cell lines. Paclitaxel and 17-AAG combination resulted in synergistic effect: paclitaxel in the combination with 17-AAG was half its original concentration and yielded similar cytotoxic effect. The dose of paclitaxel was reduced without lowering its therapeutic efficacy.