HER2-targeted gold nanoparticles potentially overcome resistance to trastuzumab in gastric cancer

Tetsushi Kubota, Shinji Kuroda, Nobuhiko Kanaya, Toshiaki Morihiro, Katsuyuki Aoyama, Yoshihiko Kakiuchi, Satoru Kikuchi, Masahiko Nishizaki, Shunsuke Kagawa, Hiroshi Tazawa, Toshiyoshi Fujiwara

Research output: Contribution to journalArticlepeer-review

15 Citations (Scopus)

Abstract

An issue of concern is that no current HER2-targeted therapeutic agent is effective against Trastuzumab (Tmab)-resistant gastric cancer. Gold nanoparticles (AuNPs) are promising drug carriers with unique characteristics of a large surface area available for attachment of materials such as antibodies. Here, we created HER2-targeted AuNPs (T-AuNPs) and examined their therapeutic efficacy and cytotoxic mechanisms using HER2-postive Tmab-resistant (MKN7) or Tmab-sensitive (NCI-N87) gastric cancer cell lines. In vitro, T-AuNPs showed stronger cytotoxic effects than controls against MKN7 and NCI-N87 cells although Tmab had no effect on MKN7 cells. Autophagy played an important role in T-AuNP cytotoxic mechanisms, which was considered to be driven by internalization of T-AuNPs. Finally, T-AuNPs displayed potent antitumor effects against NCI-N87 and MKN7 subcutaneous tumors in in vivo mouse models. In conclusion, HER2-targeted AuNPs with conjugated Tmab is a promising strategy for the development of novel therapeutic agents to overcome Tmab resistance in gastric cancer.

Original languageEnglish
Pages (from-to)1919-1929
Number of pages11
JournalNanomedicine: Nanotechnology, Biology, and Medicine
Volume14
Issue number6
DOIs
Publication statusPublished - Aug 2018

Keywords

  • Autophagy
  • Gastric cancer
  • Gold nanoparticle
  • HER2
  • Trastuzumab resistance

ASJC Scopus subject areas

  • Bioengineering
  • Medicine (miscellaneous)
  • Molecular Medicine
  • Biomedical Engineering
  • Materials Science(all)
  • Pharmaceutical Science

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