Doxorubicin- and Trastuzumab-Modified Gold Nanoparticles as Potential Multimodal Agents for Targeted Therapy of HER2+ Cancers

Abstract

Recently, targeted nanoparticles (NPs) have attracted much attention in cancer treatment due to their high potential as carriers for drug delivery. In this article, we present a novel bioconjugate (DOX–AuNPs–Tmab) consisting of gold nanoparticles (AuNPs, 30 nm) attached to chemotherapeutic agent doxorubicin (DOX) and a monoclonal antibody, trastuzumab (Tmab), which exhibited specific binding to HER2 receptors. The size and shape of synthesized AuNPs, as well as their surface modification, were analyzed by the TEM (transmission electron microscopy) and DLS (dynamic light scattering) methods. Biological studies were performed on the SKOV-3 cell line (HER2+) and showed high specificity of binding to the receptors and internalization capabilities, whereas MDA-MB-231 cells (HER2−) did not. Cytotoxicity experiments revealed a decrease in the metabolic activity of cancer cells and surface area reduction of spheroids treated with DOX–AuNPs–Tmab. The bioconjugate induced mainly cell cycle G2/M-phase arrest and late apoptosis. Our results suggest that DOX–AuNPs–Tmab has great potential for targeted therapy of HER2-positive tumors.

Keywords

• gold nanoparticles
• doxorubicin
• trastuzumab
• HER2+ cancers
• targeted therapy
• multimodality