Back to Journals » International Journal of Nanomedicine » Volume 15

Salinomycin-Loaded Small-Molecule Nanoprodrugs Enhance Anticancer Activity in Hepatocellular Carcinoma

Authors Wang J, Zhuo J, Tao Y, Xu S, Chen Z, Yang F, Ke Q, Xie H, Zheng S, Wang H, Xu X

Received 3 November 2019

Accepted for publication 10 August 2020

Published 15 September 2020 Volume 2020:15 Pages 6839—6854

DOI https://doi.org/10.2147/IJN.S236928

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 6

Editor who approved publication: Dr Mian Wang


Jianguo Wang,1,* Jianyong Zhuo,2,* Yaoye Tao,2 Shengjun Xu,2 Zun Chen,2 Fan Yang,2 Qinghong Ke,2,3 Haiyang Xie,2,3 Shusen Zheng,2– 4 Hangxiang Wang,2,3 Xiao Xu1

1Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou 310006, People’s Republic of China; 2NHC Key Laboratory of Combined Multi-Organ Transplantation, Hangzhou 310003, People’s Republic of China; 3Department of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, People’s Republic of China; 4Department of Hepatobiliary and Pancreatic Surgery, Shulan (Hangzhou) Hospital, Hangzhou 310003, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Xiao Xu
Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou 310006, People’s Republic of China
Tel/Fax +86-571-87236567
Email zjxu@zju.edu.cn

Background: There is currently no effective treatment for advanced hepatocellular carcinoma (HCC), and chemotherapy has little effect on long-term survival of HCC patients, largely due to the cancer stem cell (CSC) chemoresistance of HCC.
Methods: We constructed a small-molecule nanometer-sized prodrug (nanoprodrug) loaded with salinomycin (SAL) for the treatment of HCC. SAL was encapsulated by the prodrug LA-SN38 (linoleic acid modified 7-ethyl-10-hydroxycamptothecin) to construct a self-assembled nanoprodrug further PEGylated with DSPE-PEG2000. We characterized this codelivered nanoprodrug and its antitumor activity both in vitro in human HCC cell lines and in vivo in mice.
Results: Delivery of the SAL- and LA-SN38-based nanoprodrugs effectively promoted apoptosis of HCC cells, exerted inhibition of HCC tumor-sphere formation as well as HCC cell motility and invasion, and reduced the proportion of CD133+ HCC-CSC cells. In nude mice, the nanoprodrug suppressed growth of tumor xenografts derived from human cell lines and patient.
Conclusion: Our results show that SAL-based nanoprodrugs are a promising platform for treating patients with HCC and a novel strategy for combination therapy of cancers.

Keywords: small-molecule prodrugs, salinomycin, self-assemble, cancer stem cells, hepatocellular carcinoma

Creative Commons License This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

Download Article [PDF]  View Full Text [HTML][Machine readable]