Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 17, Issue 4, Pages -Publisher
MDPI
DOI: 10.3390/ijms17040364
Keywords
hepatoma-targeting; glycyrrhetinic acid; hyaluronic acid; micelle
Funding
- National Natural Science Foundation of China [81274093]
- Shandong Provincial Natural Science Foundation [ZR2013CL026, BS2013YY063]
- Project of Medical and Health Technology Development Program in Shandong [2013WS0284]
- Project of Chinese Medicine Research in WeiFang [2015 II 001]
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The tumor targetability and stimulus responsivity of drug delivery systems are crucial in cancer diagnosis and treatment. In this study, hepatoma-targeting mixed micelles composed of a hyaluronic acid glycyrrhetinic acid conjugate and a hyaluronic acid-L-histidine conjugate (HA-GA/HA-His) were prepared through ultrasonic dispersion. The formation and characterization of the mixed micelles were confirmed via H-1-NMR, particle size, and zeta potential measurements. The in vitro cellular uptake of the micelles was evaluated using human liver carcinoma (HepG2) cells. The antitumor effect of doxorubicin (DOX)-loaded micelles was investigated in vitro and in vivo. Results indicated that the DOX-loaded HA GA/HA His micelles showed a pH-dependent controlled release and were remarkably absorbed by HepG2 cells. Compared with free DOX, the DOX-loaded HA-GA/HA-His micelles showed a higher cytotoxicity to HepG2 cells. Moreover, the micelles effectively inhibited tumor growth in H22 cell-bearing mice. These results suggest that the HA GA/HA-His mixed micelles are a good candidate for drug delivery in the prevention and treatment of hepatocarcinoma.
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