Center for Photomedicine, Department of Biotechnology, The Catholic University of Korea, 43 Jibong-ro, Wonmi-gu, Bucheon-si, Gyeonggi-do 420-743, Korea.
Center for Photomedicine, Department of Biotechnology, The Catholic University of Korea, 43 Jibong-ro, Wonmi-gu, Bucheon-si, Gyeonggi-do 420-743, Korea.
Biomaterials. 2014 Sep;35(27):7963-9. doi: 10.1016/j.biomaterials.2014.05.063. Epub 2014 Jun 13.
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(®), 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 ∼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.
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，我们展示了一种基于光敏剂（Ce6）接枝两亲性共聚物（PF127）的单线态氧产生聚合物（SOPP）胶束，通过应用光化学内化（PCI）来克服癌症中的耐药性。载多柔比星（DOX）的 SOPP 胶束由 Ce6-PF127 缀合物自组装而成，其具有约 30nm 的均匀尺寸的球形。与游离的 Ce6 相比，由于其增加的水分散性，在水相环境中，载 DOX 的 SOPP 胶束中增强了单线态氧的生成效率。在低剂量激光功率和抗癌药物（DOX）条件下，对耐药性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）显著增加了药物（DOX）的细胞摄取，从而克服了癌细胞中的耐药性，而没有不良副作用。我们相信这种方法可能代表一种有前途的耐药性癌症治疗平台。
