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
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
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