SKIN PHOTOSENSITIVITY AND PHOTODESTRUCTION OF SEVERAL POTENTIAL PHOTODYNAMIC SENSITIZERS
SKIN PHOTOSENSITIVITY AND PHOTODESTRUCTION OF SEVERAL POTENTIAL PHOTODYNAMIC SENSITIZERS
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DOI：
10.1111/j.1751-1097.1989.tb09191.x
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发表时间：
1989-04-01
影响因子：
3.3
通讯作者：
BERNS, MW
中科院分区：
文献类型：
--
作者：
ROBERTS, WG;SMITH, KM;BERNS, MW
在临床光动力疗法中，与卟啉（Photofrin II）相关的主要副作用是皮肤光敏性。为了避免这种有害的反应，患者必须在阳光下保持大约1个月。降低皮肤光敏性的可能方法是光降解（光漂白）皮肤中的化合物。在这项研究中，我们报告了一系列的实验描述的光降解率的两个光敏剂目前受到关注，由于其潜在的用于PDT（单L-乙酰基二氢卟酚e6和磺化酞菁氯铝）。将这些化合物与Photofrin II（PfII）进行比较。实验包括测定敏化剂在（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）中国人卵巢细胞和（iv）Balb/c小鼠中的光降解速率和效率。我们使用UV蓝点灯照射的Hartely白化病豚鼠和每种致敏剂的治疗波长照射的Balb/c小鼠进行了两次标准化皮肤敏感性试验。此外，我们进行了细胞克隆形成试验比较光降解和新鲜PfII对CHO细胞。光降解的PfII表现出显着的光毒性，虽然荧光漂白超过70%。结果表明，PfII主要引起皮肤光敏化，而其他化合物基本上不产生皮肤敏感性。我们的研究表明，PfII与630 nm光的光降解的化合物的光毒性的影响不大。此外，使用405 nm光进行先前的光漂白并没有减轻皮肤敏感性。
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 photosensitizes 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.