Key Laboratory of Biomedical Polymers of Ministry of Education, Department of Chemistry, Wuhan University, Wuhan 430072, P. R. China.
Biomater Sci. 2018 Oct 24;6(11):3096-3107. doi: 10.1039/c8bm00852c.
Photodynamic therapy (PDT) as an alternative choice of cancer treatment method has attracted increasing attention in the past few decades. A sufficient amount of oxygen is essential for the production of singlet oxygen (1O2) in successful PDT; however, hypoxia is a typical hallmark of cancer, which is one of the most important limitation factors of PDT. To overcome the hypoxic tumour microenvironment and achieve highly efficient photodynamic cancer therapy, herein, a photosensitizer Ce6-loaded fluorinated polymeric micelle (Ce6-PFOC-PEI-M) was constructed via the self-assembly of an amphiphilic polymer prepared from perfluorooctanoic acid and branched polyethyleneimine (10 kDa). The introduction of perfluoroalkyl groups in the polymeric micelle Ce6-PFOC-PEI-M retained the oxygen-carrying capacity similar to perfluorocarbon, increased the oxygen level and overcame the hypoxia in C6 glioma cells under oxygen-deficient conditions. As a control, Ce6-OC-PEI-M without a perfluoroalkyl group could not increase the oxygen level in C6 glioma cells under the same conditions. With laser irradiation, Ce6-PFOC-PEI-M generated much more reactive oxygen species (ROS) in C6 glioma cells than Ce6-OC-PEI-M, leading to a higher phototoxicity in vitro and photodynamic tumour growth inhibition in vivo than Ce6-OC-PEI-M. Furthermore, there were no differences in the contents of Ce6 in tumour tissue between Ce6-PFOC-PEI-M and Ce6-OC-PEI-M. The higher efficacy of Ce6-PFOC-PEI-M in PDT is ascribed to its oxygen-carrying ability rather than higher content of Ce6 in the tumour. The presented fluorinated polymeric micelle could provide a new platform in the delivery of various photosensitizers and has great potential to improve the efficacy of PDT cancer therapy.
光动力疗法（PDT）作为癌症治疗方法的一种替代选择，在过去几十年中引起了越来越多的关注。成功的 PDT 需要有足够的氧气来产生单线态氧（1O2）；然而，缺氧是癌症的一个典型特征，这也是 PDT 的最重要限制因素之一。为了克服缺氧肿瘤微环境并实现高效的光动力癌症治疗，本文构建了一种通过两亲性聚合物自组装而成的负载光敏剂 Ce6 的氟化聚合物胶束（Ce6-PFOC-PEI-M），该聚合物由全氟辛酸和支化聚乙烯亚胺（10 kDa）制备。在聚合物胶束 Ce6-PFOC-PEI-M 中引入全氟烷基基团保留了与全氟碳类似的携氧能力，增加了氧水平，并在缺氧条件下克服了 C6 神经胶质瘤细胞中的缺氧。作为对照，不含全氟烷基基团的 Ce6-OC-PEI-M 不能在相同条件下增加 C6 神经胶质瘤细胞中的氧水平。在激光照射下，Ce6-PFOC-PEI-M 在 C6 神经胶质瘤细胞中产生的活性氧（ROS）比 Ce6-OC-PEI-M 更多，导致体外光毒性和体内光动力肿瘤生长抑制作用比 Ce6-OC-PEI-M 更高。此外，Ce6-PFOC-PEI-M 和 Ce6-OC-PEI-M 在肿瘤组织中的 Ce6 含量没有差异。Ce6-PFOC-PEI-M 在 PDT 中的更高疗效归因于其携氧能力，而不是肿瘤中 Ce6 的含量更高。所提出的氟化聚合物胶束可为各种光敏剂的递送提供新平台，并具有提高 PDT 癌症治疗效果的巨大潜力。
