演題抄録

FACO International Workshop

開催概要
開催回
第53回・2015年・京都
 

Trastuzumab-conjugated gold nanoparticles as a novel HER2-targeted therapy

演題番号 : FWS8-4

[筆頭演者]
Kuroda Shinji:1 
[共同演者]
Kubota Tetsushi:1、Morihiro Toshiaki:1、Kikuchi Satoru:1、Tazawa Hiroshi:1、Nishizaki Masahiko:1、Kagawa Shunsuke:1、Fujiwara Toshiyoshi:1

1:Gastroenterological Surgery, Graduate School of Medicine,Dentistry and Pharmaceutical Sciences, Okayama University

 

Trastuzumab (Tmab) is an antibody that binds to the human epidermal growth factor 2 (HER2) and produces antitumor effects by interfering with its signal transduction and inducing antibody-dependent cell-mediated cytotoxicity (ADCC). While Tmab is currently in clinical use for patients with HER2-positive breast cancer and gastric cancer, there remain some issues to be overcome, such as the limited application (about 20% of breast or gastric cancer population) and appearance of resistant cells. Recent progress in nanotechnology makes nanomaterials applicable in medical fields. Gold nanoparticles (AuNPs), marked by in vivo stability and easy surface modification, are known to produce antitumor effects through apoptosis and autophagy in addition to utility as diagnostic tool. In this study, we created Tmab-conjugated AuNPs (Tmab-AuNPs) and compared the antitumor effects on HER2-positive (NCI-N87 and MKN7) and -negative (MKN74) human gastric cancer cell lines with free Tmab or mixture of Tmab and AuNPs (Tmab+AuNPs) in vitro. Tmab-AuNPs showed significant antitumor effects on not only a Tmab-sensitive gastric cancer cell line (NCI-N87) but also a Tmab-resistant cell line (MKN7) compared to Tmab and Tmab+AuNPs while no significant effect was observed on MKN74 and normal human lung fibroblast (NHLF). However, once HER2 was overexpressed on MKN74 cells by adenoviral vector expressing HER2-extracellular domain, MKN74 became sensitive to Tmab-AuNPs significantly compared to Tmab and Tmab+AuNPs. IC50 of Tmab-AuNPs on NCI-N87 cells was 6 times smaller than one of Tmab, which means that a sixth of Tmab exhibited similar antitumor effects to free Tmab by being conjugated with AuNPs. In conclusion, Tmab-AuNPs have potential to become novel HER2-targeted nanodrugs which possess more potent and HER2-dependent antitumor activity than Tmab.

キーワード

臓器別:胃・十二指腸

手法別:トランスレーショナルリサーチ

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