Tumor cells-specific targeting delivery achieved by A54 peptide functionalized polymeric micelles
Tumor cells-specific targeting delivery achieved by A54 peptide functionalized polymeric micelles
复制标题
A54 肽功能化聚合物胶束实现肿瘤细胞特异性靶向递送
DOI：
10.1016/j.biomaterials.2012.08.043
复制
发表时间：
2012-12-01
期刊：
影响因子：
14
通讯作者：
Hu, Fu-Qiang
中科院分区：
文献类型：
--
作者：
Du, Yong-Zhong;Cai, Li-Li;Hu, Fu-Qiang
肿瘤靶向治疗的一个极端目标是将所有给药的化疗药物递送到肿瘤细胞中，以提高疗效并消除毒副作用。然而，迄今为止，只有部分靶向给药是通过被动靶向实现的，即所谓的“增渗保渗”效应，且仅有少数靶向给药系统实现了商业化。本文设计并合成了一种肝癌结合肽（A54肽，从噬菌体展示随机肽库中鉴定）功能化的聚乙二醇化硬脂酸接枝壳聚糖（A54-PEG-CS-SA）胶束，用于阿霉素的靶向治疗。A54-PEG-CS-SA胶束在体外与正常肝细胞共孵育时对人肝癌细胞（BEL-7402）具有特异的内化能力，在体内对肝和肝癌组织具有较高的分布能力。体内外抗肿瘤活性实验结果表明，与市售阿霉素注射剂相比，A54-PEG-CS-SA胶束载阿霉素治疗剂能更有效地抑制肿瘤生长，降低毒性。(C)2012爱思唯尔有限公司保留所有权利。
The delivery of all of administrated chemotherapeutics into tumor cells is an extreme object for tumor targeting therapy to enhance the curative effect and eliminate the side effect. However, until now, the targeting delivery has only partial been realized by passive targeting, which was called "enhanced permeability and retention" effect, and only few targeting delivery system was commercialized. Here, we designed and synthesized a hepatocarcinoma-binding peptide (A54 peptide, which was identified from a phage-display random peptide library) functionalized and PEGylated stearic acid grafted chitosan (A54-PEG-CS-SA) micelles for targeting therapy of doxorubicin. The A54-PEG-CS-SA micelles presented special internalization ability into human hepatoma cells (BEL-7402) when the cells were co-incubated with normal liver cells in vitro, and high distribution ability to liver and hepatoma tissue in vivo. In vitro and in vivo anti-tumor activity results showed that A54-PEG-CS-SA micelles loading doxorubicin treatments suppressed tumor growth more effectively and reduced toxicity compared with commercial adriamycin injection. (C) 2012 Elsevier Ltd. All rights reserved.