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Local Photodynamic Therapy of Gastrointestinal Tumors by Water-soluble Polymerized Fullerene

水溶性聚合富勒烯局部光动力治疗胃肠道肿瘤

基本信息

批准号：
10470134
负责人：
TABATA Yasuhiko
金额：
$ 7.49万
依托单位：
KYOTO UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 1999
项目状态：
已结题

项目摘要

Fullerene is known to efficiently generate singlet oxygen when irradiated with light. This will facilitate to induce a photodynamic effect on tumor, if its preferential accumulation in the tumor tissue is attained. To explore this tumor targeting of Fullerene, we chemically modified the water-insoluble fullerene with polyethylene glycol (PEG) not only to make fullerene soluble in water but also to enlarge its molecular size. When injected intravenously to mice carrying a tumor mass in the back subcutis, the large-sized, water-soluble fullerene-PEG conjugate exhibited higher accumulation and more prolonged fullerene retention in the tumor tissue than in the normal tissue. The conjugate was excreted from the body with time without being accumulated in a specific organ. Following intravenous injection of fullerene-PEG conjugates to the tumor-bearing mice coupled with exposure of the tumor site to visible light, the volume increase of the tumor mass was suppressed. Histological examination revealed that conjugate injection plus light irradiation strongly induced tumor necrosis without any damage to the overlaying normal skin. The antitumor effect of the conjugates increased with the increasing irradiation power and the fullerene dose, and the treatment with fullerene in a conjugate (424 g/kg) cured tumor at an irradiation power of 107 J/cmィイD12ィエD1. These findings indicate that the PEG-modified fullerene is a high potential agent for photodynamic tumor therapy.

富勒烯在受光照射时能有效地产生单线态氧。如果其在肿瘤组织中优先积累，将有助于诱导对肿瘤的光动力学效应。为了探索富勒烯的肿瘤靶向性，我们用聚乙二醇（PEG）对不溶于水的富勒烯进行了化学修饰，使其可溶于水，并扩大了其分子大小。将大尺寸水溶性富勒烯-聚乙二醇偶联物静脉注射到背部皮下有肿瘤的小鼠体内，在肿瘤组织中比在正常组织中积累更多，富勒烯滞留时间更长。该缀合物随时间排出体外而不积聚在特定的器官中。在荷瘤小鼠静脉注射富勒烯- peg偶联物，并将肿瘤部位暴露在可见光下，肿瘤体积的增加受到抑制。组织学检查显示，缀合物注射加光照射强烈诱导肿瘤坏死，对覆盖的正常皮肤无损伤。随着辐照功率和富勒烯剂量的增加，偶联物的抗肿瘤作用增强，在辐照功率为107 J/cm的情况下，富勒烯（424 g/kg）的偶联物可治愈肿瘤。这些结果表明，聚乙二醇修饰的富勒烯是一种很有潜力的光动力肿瘤治疗药物。