Tumoral acidic extracellular pH targeting of pH-responsive MPEG-poly (β-amino ester) block copolymer micelles for cancer therapy
Tumoral acidic extracellular pH targeting of pH-responsive MPEG-poly (β-amino ester) block copolymer micelles for cancer therapy
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DOI：
10.1016/j.jconrel.2007.07.012
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发表时间：
2007-11-06
影响因子：
10.8
通讯作者：
Kwon, Ick Chan
中科院分区：
文献类型：
--
作者：
Ko, Jinyoung;Park, Kyeongsoon;Kwon, Ick Chan
本研究的主要目的是开发和表征一种ph响应和可生物降解的聚合物胶束作为肿瘤靶向药物输送系统。以亲水性甲基醚聚乙二醇（MPEG）和ph响应性可生物降解的聚（β -氨基酯）为原料，采用michael型步进聚合法合成了ph响应型嵌段共聚物，得到了全两亲性MPEG-聚（β -氨基酯）嵌段共聚物。该共聚物在水条件下形成纳米级自组装胶束，采用溶剂蒸发法可高效（74.5%）负载阿霉素（DOX）。在一项体外药物释放研究中，这些负载DOX的聚合物胶束表现出明显的pH依赖胶束-脱胶束行为，在弱酸性环境（pH 6.4）中，DOX从胶束中快速释放，但在生理条件下（pH 7.4）释放非常缓慢。此外，由于脱胶，肿瘤细胞对聚合物胶束释放的DOX的摄取在pH 6.4时远高于pH 7.4。将负载DOX的聚合物胶束注射到B16F10荷瘤小鼠体内，评估ph响应性聚合物胶束的体内抗肿瘤活性，与游离DOX处理的小鼠相比，这些胶束显著抑制肿瘤生长，延长荷瘤小鼠的生存期。(C) 2007 Elsevier B.V.版权所有
The main objective of this study was to develop and characterize a pH-responsive and biodegradable polymeric micelle as a tumor-targeting drug delivery system. The pH-responsive block copolymer was synthesized by a Michael-type step polymerization of hydrophilic methyl ether poly (ethylene glycol) (MPEG) and pH-responsive and biodegradable poly(beta-amino ester), resulting in ail amphiphilic MPEG-poly(beta-amino ester) block copolymer. This copolymer, which formed nano-sized self-assembled micelles under aqueous conditions, could be efficiently (74.5%) loaded with doxorubicin (DOX) using a solvent evaporation method. In an in vitro drug release study, these DOX-loaded polymeric micelles showed noticeable pH-dependent micellization-demicellization behavior, with rapid release of DOX from the micelles in weakly acidic environments (pH 6.4) but very slow release under physiological conditions (pH 7.4). Moreover, due to demicellization, the tumor cell uptake of DOX released from polymeric micelles was much higher at pH 6.4 than at pH 7.4. When in vivo anti-tumor activity of pH-responsive polymeric micelles was evaluated by injecting the DOX-loaded polymeric micelles into B16F10 tumor-bearing mice, these micelles notably suppressed tumor growth and also prolonged survival of the tumor-bearing mice, compared with mice treated with free DOX. (C) 2007 Elsevier B.V. All rights reserved.