Photothermolysis mediated by gold nanorods modified with EGFR monoclonal antibody induces Hep-2 cells apoptosis in vitro and in vivo

Abstract

Shiwen Zhang,1,2,* Yunlong Li,3,4,* Xiaoguang He,2 Shouan Dong,5 Yunchao Huang,6 Xiaojiang Li,1 Yuxiao Li,2 Congguo Jin,7 Yingying Zhang,8 Yuanling Wang91Department of Head and Neck, The Third Affiliated Hospital of Kunming Medical University (Tumor Hospital of Yunnan Province), Kunming, 2Department of Head and Neck, The First Affiliated Hospital of Kunming Medical University, Kunming, 3Medical Faculty, Kunming University of Science and Technology, Kunming, 4The First People's Hospital of Yunnan Province (The Affiliated Hospital of Kunming University of Science and Technology), Kunming, 5Kunming Institute of Precious Metals, Kunming, 6Department of cardiothoracic surgery, The Third Affiliated Hospital of Kunming Medical University (Tumor Hospital of Yunnan Province), Kunming, 7Institute of Oncology, The Third Affiliated Hospital of Kunming Medical University (Tumor Hospital of Yunnan Province), Kunming, 8Clinical skills training center of Kunming Medical University, Kunming, 9Department of Anesthesiology, Yan An Hospital, Kunming, Yunnan, The People's Republic of China *These authors contributed equally to this workAbstract: Gold nanorods (AuNRs) have been used in plasmonic photothermal therapy (PPTT), which is thought to be more efficient and selective than conventional photothermal therapy. The efficiency and safety of PPTT can be improved by functionally modifying the gold nanorods with proteins or biomolecules. In this study, AuNRs were modified with anti-epidermal growth factor receptor (EGFR) monoclonal antibody (mAb), and the apoptotic potential of EGFRmAb-AuNR was assessed in Hep-2 cells in vitro and in vivo. The EGFRmAb modification had no obvious influence on the original optical property of the AuNRs, but it significantly increased the entry of AuNRs into Hep-2 cells. EGFRmAb-AuNRs, with appropriate laser irradiation, resulted in higher Hep-2 cells apoptosis than AuNRs did alone, in vitro, and was accompanied by alteration of reactive oxygen species (ROS) production, Ca2+ release, change in mitochondrial membrane potential (ΔΨm), cytochrome c (Cyt-c) release, active caspase-3 expression, and level of B-cell lymphoma 2 (Bcl-2) and B-cell lymphoma 2 protein-associated X protein (Bax). EGFRmAb-AuNR-mediated apoptosis in Hep-2 cells was also observed in vivo and had an inhibitive effect on growth of Hep-2 tumor xenografts. Our data suggest that the EGFRmAb modification improves AuNR-mediated apoptosis and may have the potential to be used clinically.Keywords: AuNRs, laryngeal squamous cancer cells, plasmonic photothermal therapy, PPTT