【摘要】 目的在光敏剂卟吩分子中通过PEG链引入靶向基团-叶酸,构建了一个新型的光敏剂Ⅰ,并评价光敏剂Ⅰ对喉癌Hep-2细胞和鼻咽癌CNE细胞的肿瘤靶向性和光动力活性。方法利用West-ern blot实验检测Hep-2细胞和CNE细胞的叶酸受体表达;采用荧光测定法评价两种细胞在有或无过量叶酸存在时对光敏剂Ⅰ的吞噬作用;采用四甲基偶氮唑蓝(MTT)试验检测光敏剂Ⅰ在有或无光照条件下对Hep-2细胞和CNE细胞的细胞毒性,以及光敏剂浓度和光照剂量对细胞存活率的影响。结果 West-ern blot实验结果表明Hep-2细胞有较强的叶酸受体表达,而CNE细胞则为叶酸受体低表达。两种细胞对光敏剂I的摄取均随光敏剂浓度的增加而增强,但Hep-2细胞的摄取能力明显强于CNE细胞(P<0.01),且过量自由叶酸的存在可竞争性地抑制Hep-2细胞对光敏剂I的摄取(P<0.01)。MTT实验结果显示在光照时,光敏剂I对Hep-2细胞和CNE细胞均有显著的光毒性,且其光动力活性与光敏剂浓度和光照剂量呈正相关性。结论光敏剂I对叶酸受体阳性表达的喉癌Hep-2细胞有明显的靶向性和光动力活性。更多还原

【Abstract】 Objective A novel photosensitizer Ⅰ was synthesized in our laboratory by linking photosensitizer chlorin with folic acid,a targeting group,through PEG linker.The aim of this paper is to evaluate the targeting and photodynamic activities of photosensitizerⅠfor laryngeal carcinoma Hep-2 cells and nasopharyngeal carcinoma CNE cells.Methods The expression of folate receptor in Hep-2 cells and CNE cells was detected by Western blot.The cellular phagocytosis of photosensitizerⅠby Hep-2 cells and CNE cells with or without the presence of excessive folic acid were tested with fluorescence spectroscopy.The cytotoxicity of photosensitizerⅠagainst Hep-2 cells and CNE cells with or without irradiation,and the effects of photosensitizer concentration and the irradiation dose on the viability of Hep-2 cells and CNE cells were measured by MTT assays.Results Western blot analysis revealed moderate expression of folate receptor in Hep-2 cells,and weak expression in CNE cells.The cellular phagocytosis of photosensitizer I by both Hep-2 cells and CNE cells increased with the concentration of photosensitizer,and the phagocytic activity of Hep-2 cells was stronger than that of CNE cells(P<0.01).The presence of excessive free folic acid could competitively inhibit the phagocytic activity of Hep-2 cells.The results of MTT assays demonstrated that photosensitizerⅠexhibited significant photocytotoxicity for both Hep-2 cells and CNE cells,and the photodynamic activity of photosensitizer I was positively correlated with the concentration of photosensitizer and the irradiation dose.Conclusion Photosensitizer I displays clear targeting and photodynamic activity for laryngeal carcinoma Hep-2 cells with high level expression of folate receptor.更多还原