Biological characterization of cetuximab-conjugated gold nanoparticles in a tumor animal model

• Published in: Nanotechnology 2014-07, Vol.25 (29), p.295102-295102
• Main Authors: Kao, Hao-Wen, Lin, Yi-Yu, Chen, Chao-Cheng, Chi, Kwan-Hwa, Tien, Der-Chi, Hsia, Chien-Chung, Lin, Wuu-Jyh, Chen, Fu-Du, Lin, Ming-Hsien, Wang, Hsin-Ell
• Format: Article
• Language: English
• Subjects: Animals; Antibodies, Monoclonal, Humanized - chemistry; Antibodies, Monoclonal, Humanized - pharmacokinetics; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - pharmacokinetics; Biological and medical sciences; Biotechnology; Carcinoma - drug therapy; Cetuximab; Cross-disciplinary physics: materials science; rheology; Disease Models, Animal; Drug delivery systems; epidermal growth factor receptor; Exact sciences and technology; Female; Fundamental and applied biological sciences. Psychology; Gold; Gold - chemistry; Gold - pharmacokinetics; gold nanoparticle; Imaging; Lung Neoplasms - drug therapy; Materials science; Methods. Procedures. Technologies; Mice; Mice, Inbred BALB C; Microspectrophotometry; Nanoconjugates - chemistry; Nanoconjugates - therapeutic use; Nanocrystalline materials; Nanoparticles; Nanoscale materials and structures: fabrication and characterization; Nanostructure; Others; Physics; radiolabeled; SPECT; Surface Plasmon Resonance; Tumor Cells, Cultured; Tumors; Uptakes; Various methods and equipments
• ISSN: 0957-4484; 1361-6528
• DOI: 10.1088/0957-4484/25/29/295102

Gold nanoparticles (AuNPs) are widely applied to the diagnosis and treatment of cancer and can be modified to contain target-specific ligands via gold-thiolate bonding. This study investigated the pharmacokinetics and microdistribution of antibody-mediated active targeting gold nanoparticles in mice with subcutaneous lung carcinoma. We conjugated AuNPs with cetuximab (C225), an antibody-targeting epidermal growth factor receptor (EGFR), and then labeled with In-111, which created EGFR-targeted AuNPs. In vitro studies showed that after a 2 h incubation, the uptake of C225-conjugated AuNPs in high EGFR-expression A549 cells was 14.9-fold higher than that of PEGylated AuNPs; furthermore, uptake was also higher at 3.8-fold when MCF7 cells with lower EGFR-expression were used. MicroSPECT/CT imaging and a biodistribution study conducted by using a A549 tumor xenograft mouse model provided evidence of elevated uptake of the C225-conjugated AuNPs into the tumor cells as a result of active targeting. Moreover, the microdistribution of PEGylated AuNPs revealed that a large portion of AuNPs remained in the tumor interstitium, whereas the C225-conjugated AuNPs displayed enhanced internalization via antibody-mediated endocytosis. Our findings suggest that the anti-EGFR antibody-conjugated AuNPs are likely to be a plausible nano-sized vehicle for drug delivery to EGFR-expressing tumors.