Enhancement of X-ray radiotherapy by specific delivery of ZHER2 affibody-conjugated gold nanoparticles to HER2-positive malignant cells

Overexpression of human epidermal growth factor receptor 2 (HER2) can be lead to cell transformation and consequently progression of various kinds of malignancies. Therefore, HER2 receptor is not just a specific target for immunotherapy using monoclonal antibodies such as trastuzumab (Herceptin (R)) but also can be considered as a targeting point for specific delivery of chemotherapeutic cargos to cancerous cells. Affibody Z(HER2) with a great affinity for HER2 receptors can be used for specific targeting of HER2-overexpressing cells. In the current study, Purified Z(HER2:342) affibody molecules were conjugated to gold nanoparticles (as X-ray radiosensitizer). Characteristics of the prepared GNPs and Z(HER2) affibody-conjugated gold nanoparticles (GNP-Z(HER2) ) were investigated by atomic force microscopy (AFM) and UV-Vis spectrophotometry. Efficacy of GNPs and GNP- Z(HER2) conjugates in enhancement of X-ray radiotherapy of four malignant cell lines including MCF-7 (a cell line with a normal expression of HER2), SK-BR-3, HN-5, and SK-OV-3 (three different HER2-overexpressing cell lines) was investigated by measuring cell viability using MTT assay. Our in vitro results showed that although sensitivity of different examined cell lines to GNP, GNP-Z(HER2) conjugate and X-ray radiation is different but in overall GNP-Z(HER2) conjugate could enhance efficacy of X-ray radiation in ablation of HER2-overexpressed cancerous cell lines.