Roberts W G, Smith K M, McCullough J L, Berns M W
Photochem Photobiol. 1989 Apr;49(4):431-8. doi: 10.1111/j.1751-1097.1989.tb09191.x.
The major side effect associated with porphyrins (Photofrin II) in clinical photodynamic therapy is skin photosensitivity. In order to avoid this deleterious reaction, patients must remain out of the sunlight for approximately 1 month. A possible procedure to reduce the amount of skin photosensitivity is to photodegrade (photobleach) the compound in the skin. In this study, we report a series of experiments describing the photodegradation rates of two photosensitizers currently receiving attention due to their potential for use in PDT (mono L-aspartyl chlorin e6 and chloroaluminum sulfonated phthalocyanine). These compounds are compared to Photofrin II (PfII). Experiments consisted of determining photodegradation rates and efficiencies of the sensitizers in (i) phosphate buffered saline (PBS), (ii) PBS with fetal calf serum (to enhance absorption and simulate cellular binding or deaggregation), (iii) Chinese Hamster Ovary cells, and (iv) Balb/c mice. We performed two standardized skin sensitivity assays using the Hartely albino guinea pig irradiated with a UV blue point lamp and Balb/c mice irradiated with the therapeutic wavelength of each sensitizer. In addition, we performed a cell clonogenicity assay comparing photodegraded and fresh PfII on CHO cells. The photodegraded PfII exhibited significant phototoxicity, although the fluorescence was bleached by more than 70%. The results show that PfII causes major skin photosensitization and that the other compounds produce no substantial skin sensitivity. Our studies suggest that photodegradation of PfII with 630 nm light has little influence on the phototoxicity of the compound. In addition, skin sensitivity was not alleviated with prior photobleaching with 405 nm light.
临床光动力疗法中与卟啉（二血卟啉醚）相关的主要副作用是皮肤光敏感性。为避免这种有害反应，患者必须在大约1个月内避免阳光照射。一种减少皮肤光敏感性的可能方法是使皮肤中的化合物发生光降解（光漂白）。在本研究中，我们报告了一系列实验，描述了两种目前因其在光动力疗法中的应用潜力而受到关注的光敏剂（单-L-天冬氨酸二氢卟吩e6和磺化铝酞菁氯）的光降解速率。将这些化合物与二血卟啉醚（PfII）进行比较。实验包括测定光敏剂在（i）磷酸盐缓冲盐水（PBS）、（ii）含胎牛血清的PBS（以增强吸收并模拟细胞结合或解聚）、（iii）中国仓鼠卵巢细胞和（iv）Balb/c小鼠中的光降解速率和效率。我们使用紫外线蓝点灯照射的Hartely白化豚鼠和用每种光敏剂的治疗波长照射的Balb/c小鼠进行了两种标准化皮肤敏感性测定。此外，我们进行了细胞克隆形成试验，比较了光降解的和新鲜的PfII对CHO细胞的影响。尽管荧光被漂白了70%以上，但光降解的PfII仍表现出显著的光毒性。结果表明，PfII会引起主要的皮肤光致敏，而其他化合物不会产生明显的皮肤敏感性。我们的研究表明，用630nm光对PfII进行光降解对该化合物的光毒性影响很小。此外，用405nm光预先光漂白并不能减轻皮肤敏感性。
