Docetaxel-based chemotherapy prolongs life and relieves symptoms in patients with castration resistant prostate cancer. However, this needs to be improved because of limitations by lack of specificity, systemic toxicity, and progression of docetaxel-resistance. Nanotechnology has served a new role in medical sciences by a variety of nanotechnology platforms, leading to theranostics. Among these platforms, Fe3O4 magnetic nanoparticles (MgNPs) have potential applications in drug delivery, cancer diagnosis and hyperthermia. We have already shown that MgNPs would modify the effect of chemotherapy in prostate cancer cells based on the observations that MgNPs increased reactive oxygen species (ROS) production and induced oxidative DNA damage in prostate cancer cell lines. Combined treatment of docetaxel and MgNPs has also shown to suppress nuclear transcription factor kappa B expression in DU145 cells. In this study, we analyzed the combined effects of docetaxel-MgNPs with different surface modifications on a prostate cancer cell line, DU145 and their mechanisms. The combination treatment of docetaxel and carboxylic acid-modified MgNPs (MgNPs-COOH) more effectively inhibited cancer cell growth and induced apoptosis compared with docetaxel-MgNPs combination. While MgNPs produced ROS in a dose-dependent manner and inhibited cancer cell growth slightly, MgNPs-COOH did exert no ROS production, however cell membrane damage in a dose-dependent manner. In addition, MgNPs-COOH showed the involvement of the endoplasmic reticulum (ER) stress. These results suggest that MgNPs-COOH may induce different responses compared with MgNPs, and result in favorable development of current chemotherapy for the advanced disease and leading to new theranostics. Citation Format: Nao Furuta, Sou Yamaguchi, Ayumi Iwasaki, Daiki Okamoto, Akiko Sato, Yoshihiro Endo, Daisuke Kurioka, Tadashi Nittami, Hitoshi Ishiguro, Hiroji Uemura, Yoshinobu Kunota, Masatoshi Watanabe. Combined effects of docetaxel-magnetic nanoparticles with different surface modifications on prostate cancer cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5501. doi:10.1158/1538-7445.AM2014-5501