Liver-Targeting and pH-Sensitive Sulfated Hyaluronic Acid Mixed Micelles for Hepatoma Therapy
Received 5 May 2019
Accepted for publication 8 November 2019
Published 2 December 2019 Volume 2019:14 Pages 9437—9452
Checked for plagiarism Yes
Review by Single-blind
Peer reviewer comments 2
Editor who approved publication: Dr Mian Wang
Zhi-peng Li,1,* Gui-xiang Tian,1,* Hong Jiang,1,* Rui-yan Pan,2 Bo Lian,1 Min Wang,1 Zhi-qin Gao,1 Bo Zhang,2 Jing-liang Wu1
1School of Bioscience and Technology, Weifang Medical University, Weifang, Shandong, People’s Republic of China; 2School of Pharmacy, Weifang Medical University, Weifang, Shandong, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Bo Zhang
School of Pharmacy, Weifang Medical University, Weifang, Shandong 261053, People’s Republic of China
School of Bioscience and Technology, Weifang Medical University, Weifang, Shandong 261053, People’s Republic of China
Tel +86 536 846 2541
Background: The tumor-targeting ability and pH-sensitive properties of intelligent drug delivery systems are crucial for effective drug delivery and anti-tumor therapy.
Methods: In this study, sHA-DOX/HA-GA mixed micelles were designed with the following properties: sulfated hyaluronic acid (sHA) was synthesized to block cell migration by inhibiting HAase; sHA-DOX conjugates were synthesized via pH-sensitive hydrazone bond to realize DOX-sensitive release. The introduction of HA-GA conjugate could improve active-targeting ability and cellular uptake.
Results: The results showed that the mixed micelles possessed a nearly spherical shape, nanoscale particle size (217.70±0.89 nm), narrow size distribution (PDI=0.07±0.04), negative zeta potential (−31.87±0.61 mV) and pH-dependent DOX release. In addition, the sHA-DOX/HA-GA micelles exhibited concentration-dependent cytotoxicities against liver carcinoma cells (HepG2) and HeLa cells, and were shown to be effectively taken up by HepG2 cells by confocal microscopy analysis. Furthermore, the in vivo anti-tumor study showed that mixed micelles had a superior anti-tumor effect compared to that of free DOX. Further evidence obtained from the hematoxylin–eosin staining and immunohistochemistry analysis also demonstrated that sHA-DOX/HA-GA exhibited stronger tumor inhibition and lower systemic toxicity than free DOX.
Conclusion: The sHA-DOX/HA-GA mixed micelles could be a potential drug delivery system for anti-hepatoma therapy.
Keywords: hyaluronic acid, glycyrrhetinic acid, hepatoma-targeting, pH-sensitive, micelles, anti-tumor therapy
This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.Download Article [PDF] View Full Text [HTML][Machine readable]