Journal
DRUG DELIVERY
Volume 28, Issue 1, Pages 2071-2084Publisher
TAYLOR & FRANCIS LTD
DOI: 10.1080/10717544.2021.1983077
Keywords
Chitosan nanoparticle; hepatocellular carcinoma; asialoglycoprotein receptor; self-assembled; liver targeting
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Funding
- National Natural Science Foundation of China [81903560, 81703606, 82174064]
- Dalian Young Star of Science and Technology Project [2018RQ81, 2020RQ068]
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The study developed novel liver-targeting chitosan nanoparticles to selectively overcome HCC via ASGPR, demonstrating strong anti-cancer efficacy and good biocompatibility. These galactosylated chitosan nanoparticles have great potential for clinical applications in treating hepatocellular carcinoma.
Hepatocellular carcinoma (HCC) is one of the major causes of cancer-related mortality worldwide. Nowadays, liver-targeting drug delivery system has been proven as a promising strategy for overcoming HCC. Asialoglycoprotein receptor (ASGPR) is an ideal receptor for liver targeting, which is mainly expressed on hepatocytes. In this study, we developed several novel liver-targeting chitosan nanoparticles to selectively overcome HCC via ASGPR. Chitosan nanoparticles (Gly-CS-VE, Gal-Gly-CS-VE, Gly-CS-DCA, and Gal-Gly-CS-DCA) were prepared by grafting hydrophilic group (glycidol, Gly), hydrophobic group (deoxycholic acid, DCA or vitamin E succinate, VE), and ASGPR recognizing group (galactose, Gal). Subsequently, their characterizations were measured by H-1 NMR, FT-IR, TEM, and DLS. Doxorubicin (DOX) was loaded in nanoparticles and released out in a pH-dependent manner. Most importantly, the galactosylated Gal-Gly-CS-VE and Gal-Gly-CS-DCA nanoparticles exhibited significantly stronger in vitro cell internalization, cytotoxicity, anti-migration capabilities and in vivo anticancer efficacies than the corresponding Gly-CS-VE and Gly-CS-DCA nanoparticles, as well as free DOX. Finally, the four chitosan nanoparticles exhibited good biocompatibility without causing any obvious histological damage to the major organs. Overall, the galactosylated chitosan nanoparticles were proven to be promising pharmaceutical formulations for selectively overcoming HCC, with great potential for clinical applications.
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