Department of Biotechnology, The Catholic University of Korea, 43 Jibong-ro, Wonmi-gu, Bucheon-si, Gyeonggi-do 420-743, Republic of Korea.
Biomaterials. 2013 Sep;34(28):6992-7000. doi: 10.1016/j.biomaterials.2013.05.070. Epub 2013 Jun 15.
To improve the cellular internalization and tumor-specific targeting efficiency of a photosensitizer, Chlorin e6 (Ce6), was conjugated to Pluronic F127(®) (PF127) by esterification between the carboxylic groups of Ce6 and the two hydroxyl groups of PF127 (PCe6). After conjugation, two different PCe6 conjugates, PF127/Ce6 (PCe6-1) and Ce6/PF127/Ce6 (PCe6-2), were obtained and separated by hydrophobic interaction chromatography. In this study, PCe6-1 was employed because it has good solubility in aqueous media. The singlet oxygen generation (SOG) efficiency and fluorescence activity of PCe6-1 in aqueous media dramatically increased compared to free Ce6. Moreover, confocal imaging and fluorescence-activated cell sorting (FACS) analysis confirmed its enhanced internalization rate in mouse colon tumor (CT-26) cells. After light irradiation, the cellular phototoxicity of PCe6-1 against CT-26 was approximately 3 times higher than that of free Ce6 in vitro. Furthermore, PCe6-1 exhibited enhanced tumor-specific distribution and tumor growth inhibition after intravenous injection into tumor-bearing mice. These results suggest that PCe6-1 is a good candidate as a photosensitizer due to its high cellular internalization rate and tumor targeting efficiency.
为了提高光敏剂氯（III）六甲川花菁（Ce6）的细胞内化和肿瘤特异性靶向效率，Ce6 的羧基与 Pluronic F127(®)（PF127）的两个羟基通过酯化反应连接，得到两种不同的 PCe6 缀合物，PF127/Ce6（PCe6-1）和 Ce6/PF127/Ce6（PCe6-2），并用疏水相互作用色谱法进行分离。在这项研究中，使用了 PCe6-1，因为它在水介质中有良好的溶解性。PCe6-1 的单线态氧生成（SOG）效率和荧光活性在水介质中比游离 Ce6 显著提高。此外，共聚焦成像和荧光激活细胞分选（FACS）分析证实了它在小鼠结肠肿瘤（CT-26）细胞中的内化率增强。光照后，PCe6-1 对 CT-26 的细胞光毒性比游离 Ce6 高约 3 倍。此外，PCe6-1 在静脉注射到荷瘤小鼠后表现出增强的肿瘤特异性分布和肿瘤生长抑制作用。这些结果表明，PCe6-1 是一种很有前途的光敏剂，因为它具有高的细胞内化率和肿瘤靶向效率。
