Silver nanoparticles coupled to anti-EGFR antibodies sensitize nasopharyngeal carcinoma cells to irradiation

Abstract

Radiotherapy is the major form of treatment for head and neck carcinoma, a malignant tumour of epithelial origin. The identification of agents, which can be co‑administered in order to sensitize these tumours to radiotherapy, has become a major focus of investigations. In the present study, a novel 20 nm nanocomposite, Ag/C225, was constructed, which consisted of silver nanoparticles (AgNPs) conjugated to an epidermal growth factor receptor‑specific antibody (C225). Physical characterization demonstrated that the Ag/C225 nanoparticles were spherical and dispersed well in water. Enzyme‑linked immunosorbent assays showed that the activity of C225 was preserved in the Ag/C225 nanoparticles. The results of 3‑(4,5‑dimethylthiazol‑2‑yl)‑2,5‑diphenyltetrazolium bromide analysis revealed that AgNPs and Ag/C225 inhibited the proliferation of nasopharyngeal carcinoma epithelial (CNE) cells in a dose‑ and time‑dependent manner. Flow cytometry revealed that AgNPs and Ag/C225 induced the apoptosis of CNEs, and abrogated G2 arrest; the latter effect was more marked with Ag/C225 than with AgNPs. Clonogenic assays indicated that AgNPs and Ag/C225 increased the sensitivity of CNEs to irradiation. The sensitizer enhancement ratios were 1.610±0.012 and 1.405±0.033 Gy for AgNPs and Ag/C225, respectively. Western blot analysis revealed that combining X‑ray irradiation with either AgNPs or Ag/C225 reduced the expression levels of DNA damage/repair proteins Ku‑70, Ku‑80 and Rad51; Ag/C225 was also more effective than AgNPs in this context. These results indicated that AgNPs and Ag/C225 effectively enhanced CNE cell radiosensitivity in vitro. Therefore, these potent agents may be considered for use as radiosensitizers during the treatment of human nasopharyngeal carcinoma.