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Cancer Photodynamic Therapy by use of RES-avoiding Liposomes

使用避免 RES 的脂质体进行癌症光动力治疗

基本信息

批准号：
07672424
负责人：
OKU Naoto
金额：
$ 1.34万
依托单位：
UNIVERSITY OF SHIZUOKA
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1995
资助国家：
日本
起止时间：
1995 至 1996
项目状态：
已结题

项目摘要

Photodynamic therapy (PDT) as a cancer treatment is notable for its quite low side effects in comparison with those of chemotherapy and radiotherapy. However, the accumulation of porphyrin derivatives used in PDT into tumor tissues is rather low. Since long-circulating liposomes are known to accumulate passively into tumor tissues, we liposomalized a porphyrin derivative, benzoporphyrin derivative monoacid ring A (BPD-MA), and used such liposomes to investigate the usefulness of PDT for tumor-bearing mice. BPD-MA was liposomalized into glucuronate-modified liposomes, which are known to be long-circulating. These liposomes were injected i.v. into Balb/c mice bearing Meth A sarcoma, and tumor regression and survival time were monitored after irradiation with laser light. Tumor regression and complete curing of tumor were observed when long circulating liposomalized BPD-MA was injected and laser-irradiated. These results suggest that a long-circulating liposomal formulation of photo-sensitive agents is useful for PDT.We also determined the liposomal trafficking by use of positron emission tomography. RES-avoinding liposomes havging long-circulating character, namely glucuronic acid-midified or PEG-modified liposomes, started to accumulate in tumor quite early after i.v. injection. Part of BPD-MA in liposomes, however, transfered to lipoproteins in the plasma, altought the liposomal formulation was useful for PDT.Therefore, liposomalization of BPD-MA should be investigated further for getting practical liposomal photosensitizer for clinical use.

光动力疗法（PDT）作为一种癌症治疗方法，与化疗和放疗相比，其副作用非常低。然而，PDT中使用的卟啉衍生物在肿瘤组织中的积累相当低。由于已知长循环脂质体被动地积聚到肿瘤组织中，我们将卟啉衍生物，苯并卟啉衍生物单酸环A（BPD-MA）脂质体化，并使用这种脂质体来研究PDT对荷瘤小鼠的有用性。将BPD-MA脂质体化为葡萄糖醛酸修饰的脂质体，已知其具有长循环性。将这些脂质体静脉注射到携带Meth A肉瘤的Balb/c小鼠中，并在用激光照射后监测肿瘤消退和存活时间。当注射长循环脂质体BPD-MA和激光照射时，观察到肿瘤消退和完全治愈。这些结果表明，长循环光敏剂脂质体制剂是有用的光动力学。我们还确定了脂质体运输使用正电子发射断层扫描。具有长循环特性的抗RES脂质体，即葡萄糖醛酸修饰的或PEG修饰的脂质体，在静脉注射后相当早地开始在肿瘤中积聚。但脂质体中的BPD-MA部分转移到血浆中的脂蛋白中，虽然脂质体制剂对PDT治疗有效，但仍需进一步研究，以获得临床实用的脂质体光敏剂。