Novel HER2-Targeted therapy combined with gold nanoparticles

Trastuzumab (Tmab) is a humanized monoclonal antibody that binds to the human epidermal growth factor receptor 2 (HER2). It is clinically used for HER2-positive breast and gastric cancers; however, the use of Tmab is restricted to tumors expressing high levels of HER2 (accounting for only 20% of tumors), and Tmab cannot be used for tumors resistant to Tmab. Although novel HER2-Targeted agents have been developed to treat Tmab-resistant tumors, none of these have shown clinical efficacy in gastric cancer patients. Recent developments in nanotechnology have had a significant impact on the field of medicine. Gold nanoparticles (AuNPs), which show characteristics such as in vivo stability and ease of surface functionali- zation, have been developed as therapeutic and contrast agents for medical applications. Previous studies show that AuNPs exert cytotoxic effects through autophagy and apoptosis; therefore, AuNPs in combination with tumor-Targeting antibodies are attractive therapeutic agents. In this study, we developed HER2-Targeted AuNPs (Tmab-AuNPs) and showed that they had a potent antitumor effect on Tmab-resistant cell lines. In addition, Tmab-AuNPs were effective against HER2-negative gastric cancer cell lines when HER2 was artificially overexpressed. Thus, our results indicate that Tmab-AuNPs may overcome the shortcomings of Tmab-based therapy.