Development of photodynamic therapy to early stage oral cancer using drug delivery system

使用药物输送系统开发早期口腔癌光动力疗法

基本信息

批准号：
11470438
负责人：
TORATANI Shigeaki
金额：
$ 3.78万
依托单位：
HIROSHIMA UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B).
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2000
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-11470438/
关键词：
photodynamic therapy liposome hematoporphyrin derivative active oxigen lipid composition of membrane squamous cell carcinoma adenocarcinoma from salivary gland 光照射扁平上皮癌

项目摘要

Photodynamic therapy (PDT) using both hematoporphyrin derivative (HPD) and photoradiation has had a high rate of effectiveness in combatting early stage cancers. We have studied, to apply this therapy to treatment of oral cancer, on verious type of cultured carcinoma cells derived from oral cancers.It has been revealed that squamous cell carcinoma cells (SCC) exhibited high sensitivity to PDT in comparison with salivary gland-derived adenocarcinoma cells (SAC). It became clear that SAC exhibited an increased level of reduced glutathion and glutathion peroxidase activity in comparison to those of SCC.The SCC which showed decreased sensitivity to PDT, exhibited a extremerly high level of glutathion S-transferase activity. Consequenly, the function of glutathion cascade were factors determining photosensitivity of the cells. In addition, the SCC demonstrated an increased intracellular level of drug compare to that SAC.So we have investigated lipid composition of cell-membrane of both cells under serum-free culture. It became evident that 60% of membrane lipids of SCC was phospholipids (PL) and 80% of those of SAC was neutral lipids (NL). The NL/PL ratio indicated that SCC showed low levels but SAC showed remarkably high levels. These result indicated that the cytotoxity of PDT correlated with the intracellular levels of drug resulted from the difference of membrane hydrophobicity.Thus, we have designed liposome which is comparable to the lipid composition of SCC cell membrane, constructed the liposome-entrapped anti-cancer drugs and examined sensitivity to this liposome of both SCC and SAC by growth assay. As the result, the liposome-entrapped drug exhibited enhanced cytotoxicity on SCC compare to either drug alone or drug-liposome mixture.

使用血源性肾上腺素衍生物（HPD）和光辐射的光动力疗法（PDT）在对抗早期癌症方面具有很高的有效性。我们研究了，将这种疗法应用于口腔癌的治疗，对来自口腔癌的毒性癌细胞类型，这表明鳞状细胞癌细胞（SCC）与盐腺衍生的腺癌细胞（SAC）相比表现出对PDT的较高敏感性。很明显，与SCC相比，SAC表现出降低的谷胱甘肽和谷胱甘肽过氧化物酶活性的降低水平。SCC对PDT的敏感性降低，表现出极端高水平的谷胱甘肽S-转移酶活性。因此，谷胱甘肽级联反应的功能是确定细胞光敏性的因素。此外，与该囊相比，SCC表现出升高的细胞内药物水平。因此，我们研究了在无血清培养物下两个细胞细胞膜的脂质组成。显然，SCC的膜脂质中有60％是磷脂（PL），而SAC的80％是中性脂质（NL）。 NL/PL比表明SCC表现出较低的水平，但SAC表现出很高的水平。这些结果表明，PDT的细胞毒性与膜疏水性差异引起的细胞内药物水平相关。因此，我们设计的脂质体与SCC细胞膜的脂质组成相媲美，它构建了脂质体 - 结束的抗癌药物和研究的lipositivitivitivity scay and scy and scy and scy and scos and scy and scy and scos and scy and scy and scy and scy and secy and secy and soce and sosos and sos and sos and sosome and sosome and sos and sosome。结果，与单独药物或药物脂质体混合物相比，SCC上脂质体的药物在SCC上表现出增强的细胞毒性。