Epirubicin-Complexed Polypeptide Micelle Effectively and Safely Treats Hepatocellular Carcinoma

Polymers

Qinglin Zhang²  Jianxun Ding³  Chenwei Lv³  Weiguo Xu³  Xun Sun¹  Xiangwei Meng² 

[1] Department of Pathology, The First Hospital of Jilin University, Changchun 130021, China;Department of Gastroenterology, The First Hospital of Jilin University, Changchun 130021, China;Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China;

关键词: chemotherapy;    electrostatic interaction;    epirubicin;    micelle;    pH-sensitivity;    polypeptide;    hepatocellular carcinoma;   

DOI  :  10.3390/polym7111521

来源: mdpi

【 摘 要 】

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related mortality worldwide. Epirubicin (EPI) once acted as a main agent for HCC chemotherapy. However, the dosage-dependent side effects seriously limit its application in clinic. The purpose of this study is to develop an effective nanocarrier to improve the efficacy and overcome the limitations of EPI. In this regard, the EPI-complexed micelle (i.e., mPEG-b-PGA/EPI) was prepared via the electrostatic interaction between the amino group in EPI and the carboxyl group in PGA segment of methoxy poly(ethylene glycol)-block-poly(l-glutamic acid) (mPEG-b-PGA), and the subsequent hydrophobic interaction among PGA/EPI complexes. The micelle appeared spherical with a diameter at around 90 nm and possessed a pH-sensitive release property of payload. The cytotoxicity and hemolysis assays in vitro, and the maximum tolerated dose tests in vivo confirmed that mPEG-b-PGA was a kind of safe material with excellent biocompatibility, while the drug-loaded micelle could obviously improve the tolerance of EPI. In addition, mPEG-b-PGA/EPI possessed significantly enhanced antitumor efficacy and security toward the H22-xenografted HCC murine model at macroscopic and microscopic levels compared with free EPI. All these results strongly indicate that mPEG-b-PGA/EPI may be a promising nanoplatform for EPI delivery in the chemotherapy of HCC.

【 授权许可】

CC BY   
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