新型光敏剂Ⅰ对头颈部肿瘤细胞的光动力活性  

Photodynamic activity of novel photosensitizer Ⅰ for tumor cells of head and neck

作　　者：李东红[1] 李鹏熙[1] 蒋宗林[2] 郭林峰[2] 

机构地区：[1]创伤,烧伤,复合伤国家重点实验室,第三军医大学大坪医院野战外科研究所第二研究室,重庆400042 [2]西华师范大学化学系,四川南充637002

出　　处：《中国耳鼻咽喉颅底外科杂志》2013年第1期38-42,47,共6页Chinese Journal of Otorhinolaryngology-skull Base Surgery

基　　金：国家自然科学基金(21072227)

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。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 photosensitizer I for 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 photosensitizer I by Hep-2 cells and CNE cells with or without the presence of excessive folic acid were tested with fluorescence spectroscopy. The cytotoxicity of photosensitizer I against 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 MTr 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 MTr assays demonstrated that photosensitizer I exhibited significant photocytotoxicity for both Hep-2 cells and CNE cells, and the photodvnamic 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 ceils with high level expression of folate receptor.

关 键 词：光敏剂Ⅰ HEP-2细胞 CNE细胞 肿瘤靶向性 光动力活性 

分 类 号：R739.91[医药卫生—肿瘤]