In vitro and in vivo evaluation of self-assembled chitosan nanoparticles selectively overcoming hepatocellular carcinoma via asialoglycoprotein receptor

Drug Delivery

Xia Lv¹  Rensong Sun²  Linlin Fang²  Yuting Wang²  Jianbin Zhang²  Zeyao Tang²  Yan Qi²  Yan Tian²  Jiani Fang²  Dapeng Chen³  Jun Chen³  Liang Wang³ 

[1] Collage of Integrative Medicine, Dalian Medical University, Dalian, Chin;Collage of Pharmacy, Dalian Medical University, Dalian, Chin;Laboratory Animal Center, Dalian Medical University, Dalian, Chin;

关键词: Chitosan nanoparticle;    hepatocellular carcinoma;    asialoglycoprotein receptor;    self-assembled;    liver targeting;   

DOI  :  10.1080/10717544.2021.1983077

来源: Taylor & Francis

【 摘 要 】

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 1H 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.

【 授权许可】

CC BY