Abstract—

It has been found that the photosensitizer 13¹-[2-(guanidinyl)ethylamino] chlorin e₆ dimethyl ester accumulates predominantly in lysosomes, partially in endosomes, and does not accumulate in mitochondria of human lung adenocarcinoma A549 cells. The primary photocytotoxic effect of the photosensitizer is associated with the damage to lysosomes and its release into the cytoplasm. In the cytoplasm, the photosensitizer is uniformly distributed in complexes with membrane structures, which serve as the secondary targets of its photoinduced effect. Time-dependent morphological signs of the development of paraptosis have been revealed, which indicate the photodynamic damage to the endoplasmic reticulum as the secondary mechanism of the photocytotoxic effect of the photosensitizer. At this stage, one more change in the potential cellular targets of the photosensitizer occurs: it concentrates in cytoplasmic and nuclear membranes, in the membranes of numerous vacuoles, and in lysosomes, which apparently continue to form during the development of paraptosis. Thus, the chlorin е₆ derivative, as a representative of hydrophobic photosensitizers with the intracellular targeting to lysosomes, has a two- or three-stage process of photodynamic action with consecutive changes in cellular targets.

中文翻译：

---

131-[2-(胍基)乙氨基]氯e6二甲酯的细胞内定位和光动力作用机制

摘要——

已发现光敏剂 13 ¹ -[2-(胍基)乙氨基] chlorin e ₆二甲基酯主要在溶酶体中积累，部分在内涵体中积累，而不在人肺腺癌 A549 细胞的线粒体中积累。光敏剂的主要光细胞毒性作用与对溶酶体的损伤及其释放到细胞质中有关。在细胞质中，光敏剂均匀分布在与膜结构的复合物中，作为其光致效应的次要靶点。已经揭示了paraptosis发展的时间依赖性形态学迹象，这表明对内质网的光动力损伤是光敏剂光细胞毒性作用的次要机制。在这个阶段，光敏剂的潜在细胞靶标发生了另一个变化：它集中在细胞质和核膜中，在许多液泡的膜和溶酶体中，它们显然在近亡的发展过程中继续形成。因此，二氢卟酚₆衍生物作为细胞内靶向溶酶体的疏水性光敏剂的代表，具有两阶段或三阶段的光动力作用过程，细胞目标连续变化。