Ochsner M
Ciba-Geigy Ltd., Physics Department, Basle, Switzerland.
J Photochem Photobiol B. 1997 May;39(1):1-18. doi: 10.1016/s1011-1344(96)07428-3.
Photodynamic therapy (PDT) is an innovative and attractive modality for the treatment of small and superficial tumours. PDT, as a multimodality treatment procedure, requires both a selective photosensitizer and a powerful light source which matches the absorption spectrum of the photosensitizer. Quadra Logic's Photofrin, a purified haematoporphyrin derivative, is so far the only sensitizer approved for phase III and IV clinical trials. The major drawbacks of this product are the lack of chemical homogeneity and stability, skin phototoxicity, unfavourable physicochemical properties and low selectivity with regard to uptake and retention by tumour vs. normal cells. Second-generation photosensitizers, including the phthalocyanines, show an increased photodynamic efficiency in the treatment of animal tumours and reduced phototoxic side effects. At the time of writing of this article, there were more than half a dozen new sensitizers in or about to start clinical trials. Most available data suggest a common mechanism of action. Following excitation of photosensitizers to long-lived excited singlet and/ or triplet states, the tumour is destroyed either by reactive singlet oxygen species (type II mechanism) and/or radical products (type I mechanism) generated in an energy transfer reaction. The major biological targets of the radicals produced and of singlet oxygen are well known today. Nucleic acids, enzymes and cellular membranes are rapidly attacked and cause the release of a wide variety of pathophysiologically highly reactive products, such as prostaglandins, thromboxanes and leukotrienes. Activation of the complement system and infiltration of immunologically active blood cells into the tumorous region enhance the damaging effect of these aggressive intermediates and ultimately initiate tumour necrosis. The purpose of this review article is to summarize the up-to-date knowledge on the mechanisms responsible for the induction of tumour necrotic reactions.
光动力疗法（PDT）是一种用于治疗小型浅表肿瘤的创新且有吸引力的方法。作为一种多模态治疗程序，PDT既需要一种选择性光敏剂，也需要一种与光敏剂吸收光谱相匹配的强大光源。Quadra Logic公司的Photofrin，一种纯化的血卟啉衍生物，是迄今为止唯一被批准用于III期和IV期临床试验的光敏剂。该产品的主要缺点是缺乏化学均一性和稳定性、皮肤光毒性、不利的物理化学性质以及在肿瘤细胞与正常细胞摄取和潴留方面的低选择性。包括酞菁类在内的第二代光敏剂在动物肿瘤治疗中显示出更高的光动力效率，并减少了光毒性副作用。在撰写本文时，有六种以上的新型光敏剂正在或即将开始临床试验。大多数现有数据表明存在一种共同的作用机制。在光敏剂被激发到长寿命的激发单线态和/或三线态后，肿瘤通过能量转移反应中产生的反应性单线态氧物种（II型机制）和/或自由基产物（I型机制）被破坏。如今，所产生的自由基和单线态氧的主要生物学靶点已为人所知。核酸、酶和细胞膜会迅速受到攻击，并导致释放出多种具有高度病理生理活性的产物，如前列腺素、血栓素和白三烯。补体系统的激活以及免疫活性血细胞向肿瘤区域的浸润增强了这些活性中间体的破坏作用，并最终引发肿瘤坏死。这篇综述文章的目的是总结关于诱导肿瘤坏死反应机制的最新知识。
