Preparation and characterization of methoxy poly(ethylene glycol)/poly(ε-caprolactone) amphiphilic block copolymeric nanospheres for tumor-specific folate-mediated targeting of anticancer drugs
Preparation and characterization of methoxy poly(ethylene glycol)/poly(ε-caprolactone) amphiphilic block copolymeric nanospheres for tumor-specific folate-mediated targeting of anticancer drugs
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DOI：
10.1016/j.biomaterials.2004.04.008
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发表时间：
2005-03-01
期刊：
影响因子：
14
通讯作者：
Lee, YM
中科院分区：
文献类型：
--
作者：
Park, EK;Lee, SB;Lee, YM
可生物降解的甲氧基聚乙二醇/聚己内酯(mpeg/PCL)两亲嵌段共聚物纳米球被设计成偶联叶酸的纳米球，以靶向在许多肿瘤细胞表面过度表达的叶酸结合蛋白。为此，端基在mpeg/PCL共聚物上的羟基被转化为伯氨基，用于与叶酸的羧基偶联。通过在有或没有抗癌剂紫杉醇的情况下形成共聚胶束来制备纳米球。比较了叶酸介导的mpeg/PCL纳米球与羟基和氨基封端的纳米球的大小、表面特征和载药效率。无论端基的类型如何，未加紫杉醇的mpeg/PCL纳米球的平均直径均为80 nm，载药后的平均直径为115 nm。Zeta电位和X射线光电子能谱测量的结果表明，叶酸分子部分暴露，并表达在纳米球的表面，使叶酸受体能够识别。在体外细胞毒性测试中，负载紫杉醇的纳米球显示出比没有紫杉醇的情况下更高的细胞存活率。因此，由mPEG和PCL组成的叶酸介导型纳米微球有可能成为肿瘤细胞选择性靶向治疗的新型药物载体。(C)2004爱思唯尔有限公司。保留所有权利。
Biodegradable methoxy poly(ethylene glycol)/poly(epsilon-caprolactone) (MPEG/PCL) amphiphilic block copolymer nanospheres coupled to folic acid have been designed to target a folate-binding protein that is overexpressed on the surface of many tumoral cells. For this purpose, hydroxy groups terminated on the MPEG/PCL copolymer were converted into primary amino groups, which were used to conjugate with the carboxylic group of folic acid. Nanospheres were prepared by the formation of micelles of the copolymer with or without the anticancer agent paclitaxel. Folate-mediated MPEG/PCL nanospheres were compared with hydroxyl- and amino-terminated nanospheres in terms of their size, surface characteristics, and drug-loading efficiency. Regardless of the type of terminal group, the MPEG/PCL nanospheres showed a narrow size distribution with an average diameter < 80 nm without paclitaxel, and an average diameter of 115 nm when loaded with the drug. The results from zeta potential and X-ray photoelectron spectroscopy measurements revealed that the folate molecules were partially exposed, and were expressed on the surface of the nanospheres allowing folate receptor recognition. In in vitro, cytotoxicity tests, the nanospheres loaded with paclitaxel showed a higher cell viability than in cases where pactitaxel was absent. Thus, folate-mediated nanospheres composed of MPEG and PCL are potentially new drug carriers for tumor cell-selective targeting treatments. (C) 2004 Elsevier Ltd. All rights reserved.