title: Enhanced cytotoxic activity of cetuximab in EGFR-positive lung cancer by conjugating with gold nanoparticles.
abstract: Cetuximab (C225) is a unique agent, targeting epidermal growth factor receptor (EGFR)-positive cancer. However, the therapeutic effect of C225 in EGFR high-expressing non-small cell lung cancer (NSCLC) remains poor. Here, we report that conjugation of C225 with gold nanoparticles (AuNPs) enhances the cytotoxicity of C225 in NSCLC both in vitro and in vivo. The NSCLC cell lines A549 (EGFR(high)) and H1299 (EGFR(low)) were employed to investigate different responses to C225, IgG-AuNPs and C225-AuNPs. The antitumor properties of C225-AuNPs were explored in vivo by establishing a tumor xenograft model in nude mice. Overall, the therapeutic effect of C225-AuNPs was more pronounced in EGFR(high) A549 cells compared with EGFR(low) H1299 cells. The cytotoxic effect of C225-AuNPs in A549 cells increased in a dose-dependent manner. C225-AuNPs significantly suppressed A549 cell proliferation and migration capacity and accelerated apoptosis compared with C225, and this effect was probably due to enhanced EGFR endocytosis and the subsequent suppression of downstream signaling pathway. Finally in the tumor xenograft of nude mice, treatment with C225-AuNPs also led to a significant reduction in tumor weight and volume with low toxicity. Our findings suggest that C225-AuNPs conjugate has promising potential for targeted therapy of EGFR positive NSCLC patients.
authors.affiliation: 1] Department of Thoracic Surgery, Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Nanjing Medical University Affiliated Cancer Hospital, Cancer Institute of Jiangsu Province, Nanjing, P.R. China 210009 [2] The First Clinical College, Nanjing Medical University, Nanjing, P.R. China 210029.
authors.forename: Yichun
authors.initials: Y
authors.lastname: Qian
authors.affiliation: 1] Department of Thoracic Surgery, Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Nanjing Medical University Affiliated Cancer Hospital, Cancer Institute of Jiangsu Province, Nanjing, P.R. China 210009 [2] The First Clinical College, Nanjing Medical University, Nanjing, P.R. China 210029.
authors.forename: Mantang
authors.initials: M
authors.lastname: Qiu
authors.affiliation: Department of Thoracic Surgery, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, P. R. China 223300.
authors.forename: Qingquan
authors.initials: Q
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Bioelectronics, Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Science and Medical Engineering, Southeast University, Nanjing, P.R. China 210096.
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Tian
authors.affiliation: State Key Laboratory of Bioelectronics, Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Science and Medical Engineering, Southeast University, Nanjing, P.R. China 210096.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Bioelectronics, Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Science and Medical Engineering, Southeast University, Nanjing, P.R. China 210096.
authors.forename: Ning
authors.initials: N
authors.lastname: Gu
authors.affiliation: Department of Oncology, Southeast University Affiliated Zhongda Hospital, Nanjing, P.R. China 210009.
authors.forename: Suyi
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Thoracic Surgery, Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Nanjing Medical University Affiliated Cancer Hospital, Cancer Institute of Jiangsu Province, Nanjing, P.R. China 210009.
authors.forename: Lin
authors.initials: L
authors.lastname: Xu
authors.affiliation: Department of Thoracic Surgery, Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Nanjing Medical University Affiliated Cancer Hospital, Cancer Institute of Jiangsu Province, Nanjing, P.R. China 210009.
authors.forename: Rong
authors.initials: R
authors.lastname: Yin
mesh_terms: D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D000068818:Cetuximab; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000378:metabolism*; D005434:Flow Cytometry; D006046:Gold / Q000008:administration & dosage* / Q000737:chemistry; D006801:Humans; D007124:Immunoenzyme Techniques; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D053768:Metal Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D051379:Mice; D008819:Mice, Nude; D047368:Tumor Burden; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D006046:Gold; C512478:EGFR protein, human; D066246:ErbB Receptors; D000068818:Cetuximab