Correlation between subcellular localization and photodynamic efficacy
Correlation between subcellular localization and photodynamic efficacy
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DOI：
10.1142/s1088424604000374
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发表时间：
2004-01-01
影响因子：
1.5
通讯作者：
Kessel, D
中科院分区：
文献类型：
--
作者：
Kessel, D
现在已经确定了多种药物可以选择性地使肿瘤细胞和其他组织对光敏感。本文根据光敏剂在体外对特定亚细胞器的初始亲和力对其进行了分类，并描述了每个主要定位位点对直接杀伤肿瘤细胞的影响。还指出了与动物模型和临床应用中功效决定因素有关的考虑因素。光动力疗法导致细胞死亡的一个后果包括Bcl-2抗凋亡成员的光损伤。这些蛋白位于内质网和线粒体膜上。直接线粒体光损伤也可引发细胞凋亡。靶向溶酶体的药物可以通过间接途径导致细胞凋亡，但这似乎并不限制它们的用途。靶向质膜的药物可以在照射过程中重新定位到细胞质溶胶，并对凋亡过程中的元件造成光损伤，导致坏死。讨论了这些发现的意义。版权所有(c) 2004年卟啉和酞菁学会。
A variety of agents have now been identified that can selectively sensitize neoplastic cells and other tissues to light. This review classifies a group of photosensitizers according to their initial affinity for specific sub-cellular organelles in vitro, and describes the consequences of each major localization site with regard to direct tumor cell kill. Considerations pertinent to determinants of efficacy in animal models and in clinical applications are also pointed out. One consequence of photodynamic therapy leading to cell death involves photodamage to anti-apoptotic members of the Bcl-2. These proteins are located on the endoplasmic reticulum and mitochondrial membranes. Direct mitochondrial photodamage can also initiate apoptosis. Agents that target lysosomes can bring about apoptotic death via an indirect route, but this does not appear to limit their usefulness. Agents that target the plasma membrane can re-localize to the cytosol during irradiation and cause photodamage to elements of the apoptotic process, resulting in necrosis. Implications of these findings are discussed. Copyright (c) 2004 Society of Porphyrins & Phthalocyanines.