TY - JOUR
T1 - HER2-targeted gold nanoparticles potentially overcome resistance to trastuzumab in gastric cancer
AU - Kubota, Tetsushi
AU - Kuroda, Shinji
AU - Kanaya, Nobuhiko
AU - Morihiro, Toshiaki
AU - Aoyama, Katsuyuki
AU - Kakiuchi, Yoshihiko
AU - Kikuchi, Satoru
AU - Nishizaki, Masahiko
AU - Kagawa, Shunsuke
AU - Tazawa, Hiroshi
AU - Fujiwara, Toshiyoshi
N1 - Funding Information:
Funding: This work was supported by Grants-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (grant number 26870390 ).
Publisher Copyright:
© 2018 Elsevier Inc.
PY - 2018/8
Y1 - 2018/8
N2 - 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.
AB - 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.
KW - Autophagy
KW - Gastric cancer
KW - Gold nanoparticle
KW - HER2
KW - Trastuzumab resistance
UR - http://www.scopus.com/inward/record.url?scp=85049343859&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85049343859&partnerID=8YFLogxK
U2 - 10.1016/j.nano.2018.05.019
DO - 10.1016/j.nano.2018.05.019
M3 - Article
C2 - 29885899
AN - SCOPUS:85049343859
SN - 1549-9634
VL - 14
SP - 1919
EP - 1929
JO - Nanomedicine: Nanotechnology, Biology, and Medicine
JF - Nanomedicine: Nanotechnology, Biology, and Medicine
IS - 6
ER -
