Engineering a Cell-Penetrating Anti-HER2 Monoclonal Antibody for Efficient Delivery of Gold Nanoparticles into Cancer Cells To Enhance X-Ray Cancer Radiation Therapy

13 INTRODUCTION Cancer heat therapy, also referred to as nanoparticle hyperthermia, utilizes the strong light absorptive properties of gold nanoparticles (GNPs) to create heat and free radicals in a small localized region to burn away cancer after GNPs absorb high energy photons from radiation (Kaur et al., 2016). Therefore, GNPs have been considered as good candidates to enhance the effect of cancer radiation therapy (Jain et al., 2012; Hu et al., 2015; Saha et al., 2016). Gold nanoparticles are gold coordination complexes with outstanding cytotoxic properties. When internalized into cells, these gold compounds can trigger direct mitochondrial damage and induce apoptosis (Gamberi, 2013). GNPs are small particles that can penetrate not only cancer cells, but also healthy tissues. Accumulation of these inherently toxic particles in healthy cells would lead to unwanted side effects and reduce the effective compound concentration at the tumor site. This lack of tumor selectivity can be addressed by attaching monoclonal antibodies (mAbs) that recognize specific cancer cell-surface proteins to the relatively large surface area of GNPs (Fay and Scott, 2011). The HER2 receptor is overexpressed in about 30% of breast cancers and regulates important pathways involved in cell survival and proliferation. Therapeutic antibodies targeting the HER2 receptor have provided satisfactory results. Additionally, HER2-targeted nanoparticles were exploited to deliver drug to tumor sites (Mazzucchelli et al., 2014). Therefore, in this study, an anti-HER2 antibody targeting HER2 receptor was conjugated to GNPs in order to specifically deliver nanoparticles to breast cancer cells for photothermal ablation. Journal of Young Investigators Research