title: Enhanced immunotherapy of SM5-1 in hepatocellular carcinoma by conjugating with gold nanoparticles and its in vivo bioluminescence tomographic evaluation.
abstract: SM5-1 is a humanized mouse monoclonal antibody, targeting an over-expressed membrane protein of approximately 230 kDa in hepatocellular carcinoma (HCC). SM5-1 can be used for target therapy in hepatocellular carinoma due to its ability of inhibiting cell growth and inducing apoptosis. However, the tumor inhibition efficacy of SM5-1 in HCC cancer treatment remains low. In this study, we synthesized SM5-1-conjugated gold nanoparticles (Au-SM5-1 NPs) and investigated their anticancer efficacy in HCC both in vitro and in vivo. The tumor inhibition rates of Au-SM5-1 NPs for subcutaneous tumor mice were 40.10% ± 4.34%, 31.37% ± 5.12%, and 30.63% ± 4.87% on day 12, 18, and 24 post-treatment as determined by bioluminescent intensity. In addition, we investigated the antitumor efficacy of Au-SM5-1 NPs in orthotopic HCC tumor models. The results showed that the inhibition rates of Au-SM5-1 NPs can reach up to 39.64% ± 4.87% on day 31 post-treatment determined by the bioluminescent intensity of the abdomen in tumor-bearing mice. Furthermore, three-dimensional reconstruction results of the orthotopic tumor revealed that Au-SM5-1 NPs significantly inhibited tumor growth compared with SM5-1 alone. Our results suggested that the developed Au-SM5-1 NPs has great potential as an antibody-based nano-drug for HCC therapy.
authors.affiliation: Key Laboratory of Molecular Imaging of Chinese Academy of Sciences, Institute of Automation, Chinese Academy of Sciences, Beijing, 100190, China; Molecular Imaging Program at Stanford (MIPS), Bio-X Program, Department of Radiology, Stanford University, CA, 94305-5344, USA; Beijing Key Laboratory of Molecular Imaging, Beijing, 100190, China.
authors.forename: Xibo
authors.initials: X
authors.lastname: Ma
authors.affiliation: Key Laboratory of Molecular Imaging of Chinese Academy of Sciences, Institute of Automation, Chinese Academy of Sciences, Beijing, 100190, China; Beijing Key Laboratory of Molecular Imaging, Beijing, 100190, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Hui
authors.affiliation: Nanomedicine and Biosensor Laboratory, School of Life Science and Technology, Harbin Institute of Technology, Harbin, 150080, China.
authors.forename: Yushen
authors.initials: Y
authors.lastname: Jin
authors.affiliation: Key Laboratory of Molecular Imaging of Chinese Academy of Sciences, Institute of Automation, Chinese Academy of Sciences, Beijing, 100190, China; Beijing Key Laboratory of Molecular Imaging, Beijing, 100190, China.
authors.forename: Di
authors.initials: D
authors.lastname: Dong
authors.affiliation: Department of Biomedical Engineering, College of Engineering, Peking University, Beijing, 100871, China.
authors.forename: Xiaolong
authors.initials: X
authors.lastname: Liang
authors.affiliation: Key Laboratory of Molecular Imaging of Chinese Academy of Sciences, Institute of Automation, Chinese Academy of Sciences, Beijing, 100190, China; Beijing Key Laboratory of Molecular Imaging, Beijing, 100190, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Yang
authors.affiliation: Educational Technology Center, The Chinese PLA General Hospital, 100853, Beijing, China.
authors.forename: Ke
authors.initials: K
authors.lastname: Tan
authors.affiliation: Department of Biomedical Engineering, College of Engineering, Peking University, Beijing, 100871, China.
authors.forename: Zhifei
authors.initials: Z
authors.lastname: Dai
authors.affiliation: Molecular Imaging Program at Stanford (MIPS), Bio-X Program, Department of Radiology, Stanford University, CA, 94305-5344, USA. Electronic address: zcheng@stanford.edu.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Cheng
authors.affiliation: Key Laboratory of Molecular Imaging of Chinese Academy of Sciences, Institute of Automation, Chinese Academy of Sciences, Beijing, 100190, China; Beijing Key Laboratory of Molecular Imaging, Beijing, 100190, China. Electronic address: jie.tian@ia.ac.cn.
authors.forename: Jie
authors.initials: J
authors.lastname: Tian
mesh_terms: D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004337:Drug Carriers / Q000737:chemistry*; D005260:Female; D006046:Gold / Q000737:chemistry*; D006801:Humans; D008099:Liver / Q000187:drug effects* / Q000473:pathology*; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000473:pathology; D053768:Metal Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D004337:Drug Carriers; D006046:Gold
keywords: Antibody therapy; Bioluminescence tomography; Cell proliferation; Gold nanoparticles; Hepatocellular carcinoma