Department of Materials Engineering, Graduate School of Engineering, The University of Tokyo, Hongo, Bunkyo-ku, Japan.
J Control Release. 2011 Nov 7;155(3):449-57. doi: 10.1016/j.jconrel.2011.06.019. Epub 2011 Jun 16.
Dendrimer phthalocyanine (DPc)-loaded polyion complex micelle (DPc/m) has been developed as photosensitizer (PS) formulation in photodynamic therapy (PDT). Incorporation of DPc into the micelle showed significant enhancement in the in vitro photocytotoxicity. Also, introduction of disulfide crosslinking in the micellar core further improved the in vitro PDT effect of DPc/m. Here, we aim to analyze the mechanism of the enhanced photocytotoxicity of DPc/m, particularly focusing on the photochemical reactions during photoirradiation. As a result, DPc/m has been shown to protect DPc from photobleaching induced by the reactions with serum proteins, although DPc were considerably quenched in the micellar core. Furthermore, the introduction of disulfide crosslinking into the micellar core has demonstrated to improve the efficiency of reactive oxygen species (ROS) production by DPc in the micellar core as well as more effectively prevent the photobleaching of DPc. These effects might lead to effective photochemical reactions by DPc/m, which may account for the enhanced photocytotoxicity. Our findings provide useful knowledge in designing PS formulations for effective PDT.
树状大分子酞菁（DPc）负载聚离子复合物胶束（DPc/m）已被开发为光动力治疗（PDT）中的光敏剂（PS）制剂。将 DPc 掺入胶束中显示出体外光细胞毒性的显著增强。此外，在胶束核中引入二硫键交联进一步提高了 DPc/m 的体外 PDT 效果。在这里，我们旨在分析 DPc/m 增强的光细胞毒性的机制，特别是关注光照射期间的光化学反应。结果表明，DPc/m 能够保护 DPc 免受与血清蛋白反应引起的光漂白，尽管 DPc 在胶束核中被相当程度地猝灭。此外，在胶束核中引入二硫键交联已被证明可以提高 DPc 在胶束核中产生活性氧（ROS）的效率，并且更有效地防止 DPc 的光漂白。这些效应可能导致 DPc/m 的有效光化学反应，这可能是增强光细胞毒性的原因。我们的研究结果为设计用于有效 PDT 的 PS 制剂提供了有用的知识。
