Self-assembled star-shaped chlorin-core poly(c-caprolactone)-poly(ethylene glycol) diblock copolymer micelles for dual chemo-photodynamic therapies
Self-assembled star-shaped chlorin-core poly(c-caprolactone)-poly(ethylene glycol) diblock copolymer micelles for dual chemo-photodynamic therapies
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DOI：
10.1016/j.biomaterials.2008.05.018
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发表时间：
2008-09-01
期刊：
影响因子：
14
通讯作者：
Lai, Ping-Shan
中科院分区：
文献类型：
--
作者：
Peng, Cheng-Liang;Shieh, Ming-Jium;Lai, Ping-Shan
合成了以甲氧基聚乙二醇（mPEG）和聚己内酯（PCL）为核的两亲性四臂星形二嵌段共聚物，并对其进行了表征。所合成的光敏剂为中心的两亲性星星嵌段共聚物形成组装的胶束状结构，可用于光动力疗法（PDT）功能化的药物递送系统。此外，疏水性化疗剂紫杉醇可以被捕获在胶束的疏水内核中。在我们的研究结果中，星形聚合物形成的胶束表现出有效的单线态氧的产生，而疏水性光敏剂由于在水溶液中聚集而失败。没有紫杉醇负载的二氢卟酚-芯胶束在MCF-7乳腺癌细胞中以7 J/cm（2）或14 J/cm（2）的光照射在二氢卟酚浓度为125 μ g/ml时表现出明显的光毒性。紫杉醇负载后，胶束粒径由71.4nm增大到103.2nm。令人惊讶的是，发现这些胶束通过中值效应分析评估的协同效应在照射后显著改善紫杉醇在MCF-7细胞中的细胞毒性。这种功能化的胶束给药系统是一种潜在的光动力学疗法和化学疗法协同组合用于治疗癌症的双重载体。皇冠版权所有（c）2008由爱思唯尔有限公司出版。保留所有权利。
Amphiphilic 4-armed star-shaped chlorin-core diblock copolymers based on methoxy poly(ethylene glycol) (mPEG) and poly(E-caprolactone) (PCL) were synthesized and characterized in this study. The synthesized photosensitizer-centered amphiphilic star block copolymer that forms assembled micelle-like structures can be used in a photodynamic therapy (PDT)-functionalized drug delivery system. Moreover, the hydrophobic chemotherapeutic agent, paclitaxel, can be trapped in the hydrophobic inner core of micelles. In our results, the star-polymer-formed micelle exhibited efficient singlet oxygen generation, whereas the hydrophobic photosensitizer failed due to aggregation in aqueous solution. The chlorin-core micelle without paclitaxel loading exhibited obvious phototoxicity in MCF-7 breast cancer cells with 7 J/cm(2) or 14 J/cm(2) light irradiation at a chlorin concentration of 125 mu g/ml. After paclitaxel loading, the size of micelle increased from 71.4 nm to 103.2 nm. Surprisingly, these micelles were found to improve the cytotoxicity of paclitaxel significantly in MCF-7 cells after irradiation through a synergistic effect evaluated by median effect analysis. This functionalized micellar delivery system is a potential dual carrier for the synergistic combination of photodynamic therapy and chemotherapy for the treatment of cancer. Crown Copyright (c) 2008 Published by Elsevier Ltd. All rights reserved.