Department of Biomedical Engineering, Case Western Reserve University, Cleveland, Wickenden Building, Rm 519, Cleveland, Ohio 44106, USA.
J Pharm Sci. 2010 May;99(5):2386-98. doi: 10.1002/jps.22007.
The silicon phthalocyanine Pc 4 is a second-generation photosensitizer that has several properties superior to other photosensitizers currently approved by the FDA, and it has shown significant promise for photodynamic therapy (PDT) in several cancer cells in vitro and model tumor systems in vivo. However, because of the high hydrophobicity of Pc 4, its formulation for in vivo delivery and favorable biodistribution become challenging. To this end, we are studying encapsulation and delivery of Pc 4 in block copolymer micelles. Here, we report the development of biocompatible PEG-PCL micelle nanoparticles, encapsulation of Pc 4 within the micelle core by hydrophobic association with the PCL block, and in vitro PDT studies of the micelle-formulated Pc 4 in MCF-7c3 human breast cancer cells. Our studies demonstrate efficient encapsulation of Pc 4 in the micelles, intracellular uptake of the micelle-formulated Pc 4 in cells, and significant cytotoxic effect of the formulation upon photoirradiation. Quantitative estimation of the extent of Pc 4 loading in the micelles and the photocytotoxicity of the micelle-incorporated Pc 4 demonstrate the promise of our approach to develop a biocompatible nanomedicine platform for tumor-targeted delivery of Pc 4 for site-selective PDT.
硅酞菁 Pc4 是第二代光敏剂，具有优于 FDA 目前批准的其他光敏剂的多种特性，在体外几种癌细胞和体内模型肿瘤系统的光动力疗法（PDT）中显示出很大的应用前景。然而，由于 Pc4 的高度疏水性，其体内传递和良好的生物分布制剂变得具有挑战性。为此，我们正在研究 Pc4 在嵌段共聚物胶束中的包封和递送。在这里，我们报告了生物相容性的 PEG-PCL 胶束纳米颗粒的开发，通过与 PCL 嵌段的疏水缔合将 Pc4 包封在胶束核内，以及 MCF-7c3 人乳腺癌细胞中胶束制剂的 Pc4 的体外 PDT 研究。我们的研究表明，Pc4 可以有效地包封在胶束中，细胞内摄取胶束制剂中的 Pc4，并且制剂在光照下具有显著的细胞毒性作用。定量估计 Pc4 在胶束中的负载程度以及胶束结合的 Pc4 的光细胞毒性表明，我们的方法具有开发用于肿瘤靶向递送 Pc4 的生物相容纳米医学平台的前景，用于位点选择性 PDT。
