期刊
INTERNATIONAL JOURNAL OF NANOMEDICINE
卷 14, 期 -, 页码 9437-9452出版社
DOVE MEDICAL PRESS LTD
DOI: 10.2147/IJN.S214528
关键词
hyaluronic acid; glycyrrhetinic acid; hepatoma-targeting; pH-sensitive; micelles; anti-tumor therapy
资金
- National Science Foundation of China [81803464]
- Natural Science Foundation of Shandong Province [ZR2018BH041]
- Education Science and Technology Project of Shandong Province [J17KA141]
- Medical and Health Technology Development Program in Shandong Province [2016WS0673]
- Project of Traditional Chinese Medicine Technology Development Program in Shandong Province [2017-212]
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.
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