Xupeng Mu,1 Fuqiang Zhang,1 Chenfei Kong,1 Hongmei Zhang,1 Wenjing Zhang,1 Rui Ge,2 Yi Liu,2 Jinlan Jiang1 1Department of Central Laboratory, China-Japan Union Hospital, 2State Key Laboratory of Supramolecular Structure and Materials, College of Chemistry, Jilin University, Changchun, China Abstract: Multifunctional nanocomposites that have multiple therapeutic functions together with real-time imaging capabilities have attracted intensive concerns in the diagnosis and treatment of cancer. This study developed epidermal growth factor receptor (EGFR) antibody-directed polydopamine-coated Fe3O4 nanoparticles (Fe3O4@PDA NPs) for magnetic resonance imaging and antitumor chemo-photothermal therapy. The synthesized Fe3O4@PDA-PEG-EGFR-DOX NPs revealed high storage capacity for doxorubicin (DOX) and high photothermal conversion efficiency. The cell viability assay of Fe3O4@PDA-PEG-EGFR NPs indicated that Fe3O4@PDA-PEG-EGFR NPs had no cell cytotoxicity. However, Fe3O4@PDA-PEG-EGFR-DOX NPs could significantly decrease cell viability (~5% of remaining cell viability) because of both photothermal ablation and near-infrared light-triggered DOX release. Meanwhile, the EGFR-targeted Fe3O4@PDA-PEG-EGFR-DOX NPs significantly inhibited the growth of tumors, showing a prominent in vivo synergistic antitumor effect. This study demonstrated the potential of using Fe3O4@PDA NPs for combined cancer chemo-photothermal therapy with increased efficacy. Keywords: Fe3O4 nanoparticles, polydopamine, chemo-photothermal therapy, multifunctional nanocomposites, DOX