Journal
INTERNATIONAL JOURNAL OF NANOMEDICINE
Volume 15, Issue -, Pages 6839-6854Publisher
DOVE MEDICAL PRESS LTD
DOI: 10.2147/IJN.S236928
Keywords
small-molecule prodrugs; salinomycin; self-assemble; cancer stem cells; hepatocellular carcinoma
Funding
- National ST Major Project [2017ZX10203205]
- National Natural Science Foundation of China [81801824]
- Key Research & Development Plan of Zhejiang Province [2019C03050]
- Major Science and Technology Project of Zhejiang Province [2018C04010]
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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 SALand 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.
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