Design and Validation of PEG-Derivatized Vitamin E Copolymer for Drug Delivery into Breast Cancer

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• 作者：Yanping Li ; Qinhui Liu ; Wenyao Li ; Ting Zhang ; Hanmei Li ; Rui Li ; Lei Chen ; Shiyun Pu ; Jiangying Kuang ; Zhiguang Su ; Zhirong Zhang ; Jinhan He
• 刊名：Bioconjugate Chemistry
• 出版年：2016
• 出版时间：August 17, 2016
• 年：2016
• 卷：27
• 期：8
• 页码：1889-1899
• 全文大小：787K
• 年卷期：0
• ISSN：1520-4812

文摘

This study examined the ability of amphiphilic poly(ethylene glycol) (PEG) derivatives to assemble into micelles for drug delivery. Linear PEG chains were modified on one end with hydrophobic vitamin E succinate (VES), and PEG and VES were mixed in different molar ratios to make amphiphiles, which were characterized in terms of critical micelle concentration (CMC), drug loading capacity (DLC), serum stability, tumor spheroid penetration and tumor targeting in vitro and in vivo. The amphiphile PEG_5K-VES₆ (PAMV₆), which has a wheat-like structure, showed a CMC of 3.03 × 10^–6 M, good serum stability, and tumor accumulation. The model drug, pirarubicin (THP), could be efficiently loaded into PAMV₆ micelles at a DLC of 24.81%. PAMV₆/THP micelles were more effective than THP solution at inducing cell apoptosis and G2/M arrest in 4T1 cells. THP-loaded PAMV₆ micelles also inhibited tumor growth much more than free THP in a syngeneic mouse model of breast cancer. PAMV₆-based micellar systems show promise as nanocarriers for improved anticancer chemotherapy.