title: [Novel HER2-Targeted Therapy Combined with Gold Nanoparticles].
abstract: Trastuzumab(Tmab)is a humanized monoclonalantibody that binds to the human epidermalgrowth 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 functionalization, 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.
authors.affiliation: Dept. of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences.
authors.forename: Tetsushi
authors.initials: T
authors.lastname: Kubota
authors.forename: Shinji
authors.initials: S
authors.lastname: Kuroda
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Morihiro
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Tazawa
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Kagawa
authors.forename: Toshiyoshi
authors.initials: T
authors.lastname: Fujiwara
mesh_terms: D019008:Drug Resistance, Neoplasm; D006046:Gold; D006801:Humans; D053768:Metal Nanoparticles / Q000008:administration & dosage*; D058990:Molecular Targeted Therapy; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000188:drug therapy*; D000068878:Trastuzumab / Q000627:therapeutic use
chemical_list: D006046:Gold; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C508053:ERBB2 protein, human