title: Biological characterization of cetuximab-conjugated gold nanoparticles in a tumor animal model.
abstract: 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.
authors.affiliation: Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Hao-Wen
authors.initials: HW
authors.lastname: Kao
authors.forename: Yi-Yu
authors.initials: YY
authors.lastname: Lin
authors.forename: Chao-Cheng
authors.initials: CC
authors.lastname: Chen
authors.forename: Kwan-Hwa
authors.initials: KH
authors.lastname: Chi
authors.forename: Der-Chi
authors.initials: DC
authors.lastname: Tien
authors.forename: Chien-Chung
authors.initials: CC
authors.lastname: Hsia
authors.forename: Wuu-Jyh
authors.initials: WJ
authors.lastname: Lin
authors.forename: Fu-Du
authors.initials: FD
authors.lastname: Chen
authors.forename: Ming-Hsien
authors.initials: MH
authors.lastname: Lin
authors.forename: Hsin-Ell
authors.initials: HE
authors.lastname: Wang
mesh_terms: D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000737:chemistry / Q000493:pharmacokinetics*; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D002277:Carcinoma / Q000188:drug therapy*; D000068818:Cetuximab; D004195:Disease Models, Animal; D005260:Female; D006046:Gold / Q000737:chemistry / Q000493:pharmacokinetics; D008175:Lung Neoplasms / Q000188:drug therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D015591:Microspectrophotometry; D058726:Nanoconjugates / Q000737:chemistry / Q000627:therapeutic use*; D020349:Surface Plasmon Resonance; D014407:Tumor Cells, Cultured
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D058726:Nanoconjugates; D006046:Gold; D000068818:Cetuximab