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用于阿霉素肝癌靶向递送的pH响应性透明质酸基混合胶束

pH-Responsive Hyaluronic Acid-Based Mixed Micelles for the Hepatoma-Targeting Delivery of Doxorubicin.

作者信息

Wu Jing-Liang, Tian Gui-Xiang, Yu Wen-Jing, Jia Guang-Tao, Sun Tong-Yi, Gao Zhi-Qin

机构信息

School of Bioscience and Technology, Weifang Medical University, Wei Fang 261053, Shandong, China.

出版信息

Int J Mol Sci. 2016 Mar 30;17(4):364. doi: 10.3390/ijms17040364.

DOI:10.3390/ijms17040364
PMID:27043540
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4848880/
Abstract

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 ¹H-NMR, particle size, and ζ 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.

摘要

药物递送系统的肿瘤靶向性和刺激响应性在癌症诊断和治疗中至关重要。在本研究中，通过超声分散制备了由透明质酸 - 甘草次酸共轭物和透明质酸 - L - 组氨酸共轭物（HA - GA/HA - His）组成的肝癌靶向混合胶束。通过¹H - NMR、粒径和ζ电位测量对混合胶束的形成和特性进行了确认。使用人肝癌（HepG2）细胞评估了胶束的体外细胞摄取。研究了载有多柔比星（DOX）的胶束的体外和体内抗肿瘤作用。结果表明，载有DOX的HA - GA/HA - His胶束表现出pH依赖性控释，并被HepG2细胞显著吸收。与游离DOX相比，载有DOX的HA - GA/HA - His胶束对HepG2细胞表现出更高的细胞毒性。此外，胶束有效抑制了荷H22细胞小鼠的肿瘤生长。这些结果表明，HA - GA/HA - His混合胶束是肝癌预防和治疗中药物递送的良好候选者。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d14/4848880/4de1e89269ba/ijms-17-00364-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d14/4848880/a97fb7cb26f1/ijms-17-00364-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d14/4848880/02378783d156/ijms-17-00364-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d14/4848880/368d81a5bd04/ijms-17-00364-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d14/4848880/20ffc0649dcb/ijms-17-00364-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d14/4848880/1311dab34a42/ijms-17-00364-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d14/4848880/4c2c159567e2/ijms-17-00364-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d14/4848880/4de1e89269ba/ijms-17-00364-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d14/4848880/a97fb7cb26f1/ijms-17-00364-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d14/4848880/a732be75acfa/ijms-17-00364-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d14/4848880/b6d34d3ddee6/ijms-17-00364-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d14/4848880/02378783d156/ijms-17-00364-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d14/4848880/368d81a5bd04/ijms-17-00364-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d14/4848880/20ffc0649dcb/ijms-17-00364-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d14/4848880/1311dab34a42/ijms-17-00364-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d14/4848880/4c2c159567e2/ijms-17-00364-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d14/4848880/4de1e89269ba/ijms-17-00364-g009.jpg

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