亚氨基二乙酸修饰四苯基卟啉光敏剂介导的光动力疗法对H22肝癌小鼠体内抗肿瘤作用的研究  

Photodynamic therapeutic effect of iminodiacetic acid modified tetraphenylporphyrin in mice bearing H22 liver cancer

作　　者：洪阁[1,2] 郭江红[1,2] 杨晓姣[1,2] 刘天军 

机构地区：[1]中国医学科学院北京协和医学院生物医学工程研究所,天津300192 [2]天津市生物医学材料重点实验室

出　　处：《国际生物医学工程杂志》2013年第3期139-142,164,F0003,共6页International Journal of Biomedical Engineering

基　　金：天津市科技支撑计划项目（12ZCDZSY11900）

摘　　要：目的评价本实验室自行合成的亚氨基二乙酸修饰四苯基卟啉光敏剂的理化性质及对H。小鼠肝癌的光动力治疗作用。方法采用紫外分光光度法测定亚氨基二乙酸修饰四苯基卟啉光敏剂的紫外吸收光谱、脂水分配系数和单线态氧产率；以肝癌H22小鼠为研究对象，随机分为空白对照组、光照组、光敏剂组、光动力治疗1次组和光动力治疗2次组，考察亚氨基二乙酸修饰四苯基卟啉光敏剂介导的光动力疗法（POT）对实体瘤的抑制率和荷瘤动物免疫机能的影响。结果亚氨基二乙酸修饰四苯基卟啉光敏剂在650nm波长处存在紫外吸收，脂水分配系数和单线态氧产率分别为2．30和0．52；单纯激光照射和单纯给予亚氨基二乙酸修饰四苯基卟啉光敏剂对肝癌H22小鼠无治疗作用（P〉0．05），而亚氨基二乙酸修饰四苯基卟啉光敏剂介导的光动力疗法对小鼠肝癌H22的生长具有极其显著的抑制作用（P〈0．001），光动力治疗2次组肿瘤抑制率高达95．15％。各治疗组对荷瘤小鼠的体质量增长、肝、脾、肺、胸腺指数几乎无影响。结论亚氨基二乙酸修饰四苯基卟啉光敏剂单线态氧产率高、两亲性好，介导的PDT抗肿瘤活性强，适合作为光动力抗肿瘤候选新药进行开发。Objective To explore the physical/chemical properties and effect of photodynamic therapy （PDT） of iminodiacetic acid modified tetraphenylporphyrin on mice bearing H22 liver cancer. Methods The UV absorbance spectrum, singlet oxygen yield and lipid-water partition coefficient were measured by UV spectrophotometry. Mice bearing H22 liver cancer as animal model were divided into control group （no drug, no light）, light treated group （no drug, only light）, drug treated group （only drug, no light）, experimental once group （with drug and light, once） and experimental twice group （with drug and light, twice, PDT twice）. Tumor inhibition rate and index of liver, spleen, lung, thymus of the mice were calculated to evaluate the antitumor activity of iminodiacetic acid modified tetraphenyl porphyrin-PDT. Results The iminodiacetic acid modified tetraphenylporphyrin had absorption at 650 nm, while its singlet oxygen yield and lipid-water partition coefficient were 2.30 and 0.52, respectively. No antitumor effect on mice bearing HE21iver cancer for light treated group and drug treated group respectively. However, significant antitumor effect （P〈0.001）was found at experimental group. The maximum tumor inhibition rate could be 95.15% for PDT twice group. No significant differences were observed on weight gain and liver, lung, spleen, thymus index in each group. Conclusion Iminodiacetic acid modified tetraphenylporphyfin with high singlet oxygen yield, low toxicity and significant in vivo anti-tumor activity, is suitable to be developed as an anti-tumor drug candidate for photodynamic therapy.

关 键 词：亚氨基二乙酸修饰四苯基卟啉 光动力疗法 肝癌H22 脂水分配系数 单线态氧 

分 类 号：R735.7[医药卫生—肿瘤]