Dual targeting system by supramolecular complex of folate-conjugated methyl-β-cyclodextrin with adamantane-grafted hyaluronic acid for the treatment of colorectal cancer
Dual targeting system by supramolecular complex of folate-conjugated methyl-β-cyclodextrin with adamantane-grafted hyaluronic acid for the treatment of colorectal cancer
复制标题
DOI：
10.1016/j.ijbiomac.2018.02.149
复制
发表时间：
2018-07-01
影响因子：
8.2
通讯作者：
Arima, Hidetoshi
中科院分区：
文献类型：
--
作者：
Elamin, Khaled M.;Motoyama, Keiichi;Arima, Hidetoshi
Please try later.
In our previous study, we demonstrated that folate-appended methyl cyclodextrin (FA-M-beta-CyD) was a promising antitumor agent for the treatment of folate receptor-alpha (FR-alpha)-expressing tumors. In the present study, to enhance the antitumor effect of FA-M-beta-CyD against FR-alpha- and CD44-expressing colorectal cancer cells, we synthesized a dual targeting supramolecular complex composed of FA-M-beta-CyD and adamantane-grafted hyaluronic acid (Ad-HA). The supramolecular complex of Ad-HA/FA-M-beta-CyD showed higher cytotoxic activity in HCT116 cells (FR-alpha (+), CD44 (+)), a human colon cancer cell line, than FA-M-beta-CyD alone. In addition, the cytotoxic activity of Ad-HA/FA-M-beta-CyD was significantly impaired by the addition of FA and HA, as inhibitors of FR-alpha and CD44, respectively. Furthermore, tetramethylrhodamine isothiocyanate (TRITC)-labeled FA-M-beta-CyD was efficiently internalized into HCT116 cells through supramolecular complexation with Ad-HA, compared to that of TRITC-FA-M-beta-CyD alone. Additionally, Ad-HA/FA-M-beta-CyD induced mitophagy in HCT116 cells. These results suggest that Ad-HA/FA-M-beta-CyD targeted HCT116 cells, as well as induced mitophagy-mediated cell death. Notably, an intravenous injection of the Ad-HA/FA-M-beta-CyD complex in a mouse model of colorectal cancer significantly ameliorated the growth of tumor polyps. Collectively, these results suggest that Ad-HA/FA-M-beta-CyD has antiproliferation effects in tumors, based on the dual targeting activity. (C) 2018 Elsevier B.V. All rights reserved.