Jiménez-Banzo Ana, Sagristà M Luisa, Mora Margarita, Nonell Santi
Grup d'Enginyeria Molecular, Institut Químic de Sarrià, Universitat Ramon Llull, Via Augusta 390, 08017 Barcelona, Spain.
Free Radic Biol Med. 2008 Jun 1;44(11):1926-34. doi: 10.1016/j.freeradbiomed.2008.02.011. Epub 2008 Mar 6.
The roles played by singlet oxygen ((1)O(2)) in photodynamic therapy are not fully understood yet. In particular, the mobility of (1)O(2) within cells has been a subject of debate for the last two decades. In this work, we report on the kinetics of (1)O(2) formation, diffusion, and decay in human skin fibroblasts. (1)O(2) has been photosensitized by two water-soluble porphyrins targeting different subcellular organelles, namely the nucleus and lysosomes, respectively. By recording the time-resolved near-IR phosphorescence of (1)O(2) and that of its precursor the photosensitizer's triplet state, we find that the kinetics of singlet oxygen formation and decay are strongly dependent on the site of generation. (1)O(2) photosensitized in the nucleus is able to escape out of the cells while (1)O(2) photosensitized in the lysosomes is not. Despite showing a lifetime in the microsecond time domain, (1)O(2) decay is largely governed by interactions with the biomolecules within the organelle where it is produced. This observation may reconcile earlier views that singlet oxygen-induced photodamage is highly localized, while its lifetime is long enough to diffuse over long distances within the cells.
单线态氧（(1)O(2)）在光动力疗法中所起的作用尚未完全明了。特别是，(1)O(2)在细胞内的移动性在过去二十年里一直是一个争论的话题。在这项工作中，我们报告了(1)O(2)在人皮肤成纤维细胞中的生成、扩散和衰变动力学。(1)O(2)已被两种分别靶向不同亚细胞器（即细胞核和溶酶体）的水溶性卟啉光敏化。通过记录(1)O(2)及其前体光敏剂三重态的时间分辨近红外磷光，我们发现单线态氧的生成和衰变动力学强烈依赖于生成位点。在细胞核中光敏化的(1)O(2)能够逸出细胞，而在溶酶体中光敏化的(1)O(2)则不能。尽管(1)O(2)在微秒时域内显示出一定寿命，但其衰变很大程度上受其产生所在细胞器内生物分子相互作用的支配。这一观察结果可能调和了早期的观点，即单线态氧诱导的光损伤高度局限，而其寿命又足够长，能够在细胞内远距离扩散。
