Liver-Targeting and pH-Sensitive Sulfated Hyaluronic Acid Mixed Micelles for Hepatoma Therapy
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, Wei...
Guardado en:
| Autores principales: | , , , , , , , , |
|---|---|
| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Dove Medical Press
2019
|
| Materias: | |
| Acceso en línea: | https://doaj.org/article/8c211f6a530b405eb97b1a205a3154d7 |
| Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
| Sumario: | 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 workCorrespondence: Bo ZhangSchool of Pharmacy, Weifang Medical University, Weifang, Shandong 261053, People’s Republic of ChinaEmail bozh315@163.comJing-liang WuSchool of Bioscience and Technology, Weifang Medical University, Weifang, Shandong 261053, People’s Republic of ChinaTel +86 536 846 2541Email jlwu2008@163.comBackground: 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 |
|---|