Improvement of specific aiming of X-ray radiotherapy on HER2-overexpressing cancerous cell lines by targeted delivery of silver nanoparticle

Abstract

Human epidermal growth factor receptor 2 (HER2) as a member of epidermal growth factor receptor (EGFR) family is expressed in various kinds of malignant cells at a level higher than normal cells. Therefore, HER2 could be consider as a target for specific chemotherapy and selective ablation of cancerous cells. ZHER2 affibody as an engineered peptide with great affinity for HER2 receptor could be employed for specific targeting of cancer cells with high HER2 expression level. On the other hand, X-ray radiotherapy is one of the most prevalent approaches in cancer therapy and nanoparticles with high atomic number could enhance its efficiency. As an outcome, targeted delivery of these nanoparticles can increase intensity and focus of X-ray radiation on cancerous cells. In the current in vitro study, silver nanoparticles (AgNPs) in conjugations with ZHER2 affibody were investigated for enhancement of X-ray radiation therapy of HER2-positive cancerous cells originated from various kinds of malignancies. Cell lines with high expression of HER2 (SK-BR-3, HN-5, SK-OV-3) and also MCF-7 cell line with normal expression of HER2 were irradiated with X-ray in the presence of various concentrations of AgNPs or AgNP-ZHER2 conjugates. Morphology and size of prepared AgNPs and AgNP-ZHER2 were examined by atomic force microscopy (AFM) and dynamic light scattering (DLS). Success of conjugation was confirmed by UV–Vis spectroscopy and viability of treated cells was assessed by MTT assay. Our results showed that while sensitivity of four examined cell lines to AgNPs, AgNP-ZHER2, and X-ray radiation is different, but presence of AgNP-ZHER2 conjugate could significantly enhance efficiency of X-ray radiation in ablation of HER2-overexpressed cells at in vitro conditions.