Doxorubicin loaded singlet-oxygen producible polymeric micelle based on chlorine e6 conjugated pluronic F127 for overcoming drug resistance in cancer
Doxorubicin loaded singlet-oxygen producible polymeric micelle based on chlorine e6 conjugated pluronic F127 for overcoming drug resistance in cancer
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DOI：
10.1016/j.biomaterials.2014.05.063
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发表时间：
2014-09-01
期刊：
影响因子：
14
通讯作者：
Na, Kun
中科院分区：
文献类型：
--
作者：
Park, Hyung;Park, Wooram;Na, Kun
耐药性仍然是癌症化疗成功的主要障碍之一。在这项工作中，我们展示了基于光敏剂（PS，二氢卟酚e6（Ce 6））缀合的两亲性共聚物（pluronic F127（R），PF 127）的单线态氧可产生聚合物（SOPP）胶束，用于通过应用光化学内化（PCI）克服癌症中的耐药性。由Ce 6-PF 127偶联物自组装得到了阿霉素（DOX）-SOPP胶束，该胶束为球形，大小约为30 nm。与游离Ce 6相比，由于其水分散性的提高，负载DOX的SOPP胶束在水性环境中的单线态氧生成效率增强。在低剂量的激光功率和抗癌药物（DOX）条件下，对耐药癌细胞的体外和体内研究表明，单线态氧介导的细胞膜损伤（由脂质过氧化引起）显著增加了细胞对药物（DOX）的摄取，从而导致克服癌细胞的耐药性而没有不良副作用。我们相信这种方法可以代表耐药癌症治疗的一个有前途的平台。(C)2014爱思唯尔有限公司版权所有。
Drug resistance remains one of the primary obstacles to the success of cancer chemotherapy. In this work, we demonstrate a singlet-oxygen producible polymeric (SOPP) micelle based on photosensitizer (PS, chlorin e6 (Ce6)) conjugated amphiphilic copolymer (pluronic F127 (R), PF127) for overcoming drug resistance in cancer by applying photochemical internalization (PCI). The doxorubicin (DOX)-loaded SOPP micelles were self-assembled from Ce6-PF127 conjugates, which have a spherical shape with a uniform size of similar to 30 nm. Compared with free Ce6, enhanced singlet-oxygen generation efficiency in the DOX-loaded SOPP micelles have been demonstrated in aqueous environments due to their increased water-dispersibility. Under low dose of laser power and anti-cancer drug (DOX) conditions, in vitro and in vivo studies on drug-resistant cancer cells demonstrated that singlet-oxygen-mediated cellular membrane damage (caused by lipid peroxidation) significantly increased the cellular uptake of drug (DOX), which led to overcoming the drug resistance in cancer cells without undesirable side effects. We believe this approach could represent a promising platform for drug-resistant cancer treatment. (C) 2014 Elsevier Ltd. All rights reserved.