Yuan Pan, Ruan Zheng, Jiang Wei, Liu Le, Dou Jiaxiang, Li Tuanwei, Yan Lifeng
CAS Key Laboratory of Soft Matter Chemistry, and Department of Chemical Physics, iCHEM, University of Science and Technology of China, P. R. China.
J Mater Chem B. 2018 Apr 21;6(15):2323-2331. doi: 10.1039/c8tb00493e. Epub 2018 Apr 3.
A major hindrance for photodynamic therapy (PDT) to achieve higher efficiency is the hypoxia environment in the tumor area and the PDT-induced continuous consumption of molecular oxygen. Oxygen self-sufficient fluorinated polypeptide nanoparticles have been synthesized via the loading of a NIR photosensitizer (BODIPY-Br) into a water-dispersible drug delivery system for high efficiency PDT. As a result of the higher oxygen capacity and O lifetime enhancement of perfluorocarbon, the whole PDT agent demonstrated higher oxygen uptake and enhanced singlet oxygen production, showing the potential to improve the PDT efficacy in hypoxia tumor environments after light irradiation. In vitro studies including cellular uptake and PDT efficiency were evaluated using hepatocellular carcinoma HepG2 cells as models, and the enhanced PDT efficiency of fluorinated polypeptide DDS with higher O content was measured on a tumor-bearing BALB/c mice model by in vivo experiments. Results demonstrated that the fluorinated polypeptide platform plays a significant role as an effective delivery vehicle for small molecule photosensitizers while increasing the generation of reactive oxygen species (ROS) and having higher cytotoxicity to cancer cells, especially in the hypoxia environment. In addition, the BODIPY-Br photosensitizer worked for both PDT and imaging in the NIR region making it a potential theranostic for cancer treatment.
光动力疗法（PDT）实现更高效率的一个主要障碍是肿瘤区域的缺氧环境以及PDT引起的分子氧持续消耗。通过将近红外光敏剂（BODIPY-Br）负载到水分散性药物递送系统中，合成了氧自足的氟化多肽纳米颗粒，用于高效PDT。由于全氟碳具有更高的氧容量和更长的氧寿命，整个PDT剂表现出更高的氧摄取和增强的单线态氧产生，显示出在光照射后改善缺氧肿瘤环境中PDT疗效的潜力。以肝癌HepG2细胞为模型评估了包括细胞摄取和PDT效率在内的体外研究，并通过体内实验在荷瘤BALB/c小鼠模型上测量了具有更高氧含量的氟化多肽药物递送系统增强的PDT效率。结果表明，氟化多肽平台作为小分子光敏剂的有效递送载体发挥着重要作用，同时增加活性氧（ROS）的产生并对癌细胞具有更高的细胞毒性，尤其是在缺氧环境中。此外，BODIPY-Br光敏剂在近红外区域可用于PDT和成像，使其成为癌症治疗的潜在诊疗试剂。
