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

• Main Authors: Wang J, Zhuo J, Tao Y, Xu S, Chen Z, Yang F, Ke Q, Xie H, Zheng S, Wang H, Xu X
• Format: Article
• Language: English
• Published: Dove Medical Press 2020-09-01
• Series: International Journal of Nanomedicine
• Subjects: small-molecule prodrugs; salinomycin; self-assemble; cancer stem cells; hepatocellular carcinoma
• Online Access: https://www.dovepress.com/salinomycin-loaded-small-molecule-nanoprodrugs-enhance-anticancer-acti-peer-reviewed-article-IJN
• ISSN: 1178-2013

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 workCorrespondence: Xiao XuDepartment of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou 310006, People’s Republic of ChinaTel/Fax [phone]Email [e-mail]: 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