BACTERIOCHLOROPHYLL-A AS PHOTOSENSITIZER FOR PHOTODYNAMIC TREATMENT OF TRANSPLANTABLE MURINE TUMORS
BACTERIOCHLOROPHYLL-A AS PHOTOSENSITIZER FOR PHOTODYNAMIC TREATMENT OF TRANSPLANTABLE MURINE TUMORS
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DOI：
10.1016/1011-1344(91)80016-b
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发表时间：
1991-09-01
影响因子：
5.4
通讯作者：
DOUGHERTY, TJ
中科院分区：
文献类型：
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作者：
HENDERSON, BW;SUMLIN, AB;DOUGHERTY, TJ
在SMT-F和RIF可移植小鼠肿瘤系统中测试了吸收780 nm波长的光的细菌叶绿素a（bChla）的体内光动力活性。组织提取物的高效液相色谱（HPLC）分析表明，bChla在体内迅速降解为细菌脱镁叶绿素a（bPheoa）和其他分解产物。这些也是光动力学活性的，并且可以在660至780 nm的波长范围内实现肿瘤响应，而肿瘤治愈限于755（bPheoa）至780 nm的波长。在660 nm处吸收的光敏化产物也存在于分离的肿瘤细胞中。光动力学细胞杀死的肿瘤细胞分离的肿瘤细胞后，bChla积累在体内，使用755或780 nm的光在体外，是指数高达20-40 J cm-2。超过该光剂量，几乎没有或没有进一步的损害可以实现，这是这些敏化剂的快速光漂白的指示。在体内，血管闭塞容易发生，如果光治疗后不久，敏化剂管理，但延迟，如果光治疗后24小时进行注射。虽然高达70%的肿瘤细胞在体内光治疗完成后被致命的破坏，同时严重的血管破坏似乎是必要的肿瘤治愈。正常组织光敏性在给药后5天内完全消退。
Bacteriochlorophyll-a (bChla), which absorbs light of 780 nm wavelength, was tested for in vivo photodynamic activity in the SMT-F and RIF transplantable mouse tumor systems. High performance liquid chromatography (HPLC) analysis of tissue extracts showed that bChla was rapidly degraded in vivo to bacteriopheophytin-a (bPheoa) and other breakdown products. These were also photodynamically active, and tumor response could be achieved over a wavelength range of 660 to 780 nm, while tumor cure was restricted to wavelengths of 755 (bPheoa) to 780 nm. A photosensitizing product absorbing at 660 nm was also present in isolated tumor cells. Photodynamic cell kill of tumor cells isolated from tumors after bChla accumulation in vivo, using 755 or 780 nm light in vitro, was exponential up to 20-40 J cm-2. Above this light dose little or no further damage could be achieved, which is an indication of the rapid photobleaching of these sensitizers. In vivo, vascular occlusion occurred readily if light treatment was delivered shortly after sensitizer administration, but was delayed if light treatment was carried out 24 h after injection. Although up to 70% of tumor cells were lethally damaged after completion of in vivo light treatment, concurrent severe vascular destruction seemed necessary for tumor cure. Normal tissue photosensitivity totally subsided within 5 days after sensitizer administration.