Morgan J, Gray A G, Huehns E R
Department of Haematology, University College, Middlesex School of Medicine, London, UK.
Br J Cancer. 1989 Mar;59(3):366-70. doi: 10.1038/bjc.1989.73.
A partially purified fraction of the water soluble photosensitive dye sulphonated aluminium phthalocyanine (AlSPc) was encapsulated in liposomes which were then linked to a targeting monoclonal antibody 791T/36 using a heterobifunctional linking agent. The photocytotoxic effects of the liposomes were determined on two cell lines bearing an antigen with which the targeting antibody binds: 791T, an osteosarcoma and C170, a colorectal carcinoma; and a control cell line not bearing the antigen; DW-BCL, an Epstein-Barr virus immortalised B-cell line. Antibody dependent cytotoxicity was observed in 791T and C170 cells and was proportional to the number of antigens on the cells, the AlSPc concentration and the time of exposure to activating red light. No significant toxicity was seen using untargeted liposomes, control cells or free AlSPc fraction under similar conditions. Targeted cells and controls kept in the dark also showed no significant toxicity. A possible mechanism of action is postulated and simple adaptations which demonstrate the versatility of the model are discussed. Some suggestions as to the clinical situations to which this system might be applied in the form of photodynamic therapy (PDT) are made.
将水溶性光敏染料磺化铝酞菁(AlSPc)的部分纯化级分包裹于脂质体中,然后使用异双功能连接剂将脂质体与靶向单克隆抗体791T/36相连。在两种带有与靶向抗体结合抗原的细胞系上测定脂质体的光细胞毒性:791T,一种骨肉瘤细胞系;C170,一种结肠癌细胞系;以及一种不带有该抗原的对照细胞系;DW-BCL,一种爱泼斯坦-巴尔病毒永生化B细胞系。在791T和C170细胞中观察到抗体依赖性细胞毒性,且其与细胞上抗原的数量、AlSPc浓度以及暴露于激活红光的时间成正比。在相似条件下,使用非靶向脂质体、对照细胞或游离AlSPc级分未观察到明显毒性。处于黑暗中的靶向细胞和对照也未显示明显毒性。推测了一种可能的作用机制,并讨论了展示该模型通用性的简单改良方法。针对该系统可能以光动力疗法(PDT)形式应用的临床情况提出了一些建议。