In vivo and in vitro photodynamic studies with benzochlorin iminium salts delivered by a lipid emulsion
In vivo and in vitro photodynamic studies with benzochlorin iminium salts delivered by a lipid emulsion
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DOI：
10.1562/0031-8655(1998)068
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发表时间：
1998-10-01
影响因子：
3.3
通讯作者：
Morgan, AR
中科院分区：
文献类型：
--
作者：
Garbo, GM;Fingar, VH;Morgan, AR
苯并二氢亚胺盐 (BI) 是基于八乙基苯并二氢核的疏水性光敏剂，可吸收可见光谱的近红外区域。在这些研究中，在携带乳腺癌肿瘤系的 C3H-HeJ 小鼠体内比较了不含锌、铜和金属的 BI 衍生物的光动力活性。还对放射诱导的纤维肉瘤肿瘤系进行了体外研究。使用氩泵浦钛蓝宝石激光器调谐以提供 710 至 800 mn 之间的光，或使用经过滤以提供 590 nm 以上宽带光的 Oriel 弧光灯作为光源。在所有研究中都使用脂肪乳剂作为敏化剂的递送系统。对于所检查的所有亚胺盐中的每一种，观察到 Q 带具有明显的溶剂依赖性。例如，无金属 (BI) 衍生物在二氯甲烷中的最大吸收波长为 798 nm，在血清中的最大吸收波长为 727 nm。作用光谱显示，三种亚胺盐在体内和体外均在蓝移波长下具有更大的 PDT 响应。在这三种衍生物中，锌类似物（ZnBI）在0.7（μmol/kg和200 J/cm（2））的低药物/光剂量下产生最大的肿瘤消退。这些结果表明亚胺盐具有可能使其成为有希望的第三代光敏剂的特性。
Benzochlorin iminium salts (BIs) are hydrophobic photosensitizers based on an octaethylbenzochlorin nucleus that absorb in the near-IR region of the visible spectrum. lo these studies the photodynamic activities of the zinc, copper and metal-free BI derivatives were compared in vivo in C3H-HeJ mice bearing a mammary adenocarcinoma tumor line. In vitro studies were also performed with the radiation-induced fibrosarcoma tumor line. An argon-pumped Ti-sapphire laser tuned to deliver light between 710 and 800 mn or an Oriel are-lamp filtered to deliver broadband light above 590 nm were used as light source. A lipid emulsion was used as the delivery system for sensitizers in all studies. A pronounced solvent dependence was observed for the Q band for each of all iminium salts examined. As an example, the metal-free (BI) derivative had an absorption maximum at 798 nm in dichloromethane and at 727 nm in serum. The action spectra showed a greater PDT response at blue-shifted wavelengths for each of the three iminium salts both in vivo and in vitro. Among the three derivatives, the zinc analog (ZnBI) produced the greatest tumor regression at the low drug/light dose of 0.7 (mu mole/kg and 200 J/cm(2). These results indicate that iminium salts have characteristics that may make them promising third-generation photosensitizers.