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Polymers 2015, 7(11), 2410-2430; doi:10.3390/polym7111521

Epirubicin-Complexed Polypeptide Micelle Effectively and Safely Treats Hepatocellular Carcinoma

1
Department of Gastroenterology, The First Hospital of Jilin University, Changchun 130021, China
2
Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China
3
Department of Pathology, The First Hospital of Jilin University, Changchun 130021, China
*
Author to whom correspondence should be addressed.
Academic Editor: Carsten Werner
Received: 17 October 2015 / Revised: 7 November 2015 / Accepted: 19 November 2015 / Published: 24 November 2015
(This article belongs to the Special Issue Functional Polymers for Medical Applications)
View Full-Text   |   Download PDF [9168 KB, uploaded 24 November 2015]   |  

Abstract

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. View Full-Text
Keywords: chemotherapy; electrostatic interaction; epirubicin; micelle; pH-sensitivity; polypeptide; hepatocellular carcinoma chemotherapy; electrostatic interaction; epirubicin; micelle; pH-sensitivity; polypeptide; hepatocellular carcinoma
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Zhang, Q.; Ding, J.; Lv, C.; Xu, W.; Sun, X.; Meng, X. Epirubicin-Complexed Polypeptide Micelle Effectively and Safely Treats Hepatocellular Carcinoma. Polymers 2015, 7, 2410-2430.

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