Berg K, Selbo P K, Weyergang A, Dietze A, Prasmickaite L, Bonsted A, Engesaeter B Ø, Angell-Petersen E, Warloe T, Frandsen N, Høgset A
Department of Radiation Biology, The Norwegian Radium Hospital, Oslo, Norway.
J Microsc. 2005 May;218(Pt 2):133-47. doi: 10.1111/j.1365-2818.2005.01471.x.
A photosensitizer is defined as a chemical entity, which upon absorption of light induces a chemical or physical alteration of another chemical entity. Some photosensitizers are utilized therapeutically such as in photodynamic therapy (PDT) and for diagnosis of cancer (fluorescence diagnosis, FD). PDT is approved for several cancer indications and FD has recently been approved for diagnosis of bladder cancer. The photosensitizers used are in most cases based on the porphyrin structure. These photosensitizers generally accumulate in cancer tissues to a higher extent than in the surrounding tissues and their fluorescing properties may be utilized for cancer detection. The photosensitizers may be chemically synthesized or induced endogenously by an intermediate in heme synthesis, 5-aminolevulinic acid (5-ALA) or 5-ALA esters. The therapeutic effect is based on the formation of reactive oxygen species (ROS) upon activation of the photosensitizer by light. Singlet oxygen is assumed to be the most important ROS for the therapeutic outcome. The fluorescing properties of the photosensitizers can be used to evaluate their intracellular localization and treatment effects. Some photosensitizers localize intracellularly in endocytic vesicles and upon light exposure induce a release of the contents of these vesicles, including externally added macromolecules, into the cytosol. This is the basis for a novel method for macromolecule activation, named photochemical internalization (PCI). PCI has been shown to potentiate the biological activity of a large variety of macromolecules and other molecules that do not readily penetrate the plasma membrane, including type I ribosome-inactivating proteins, immunotoxins, gene-encoding plasmids, adenovirus, peptide-nucleic acids and the chemotherapeutic drug bleomycin. The background and present status of PDT, FD and PCI are reviewed.
光敏剂被定义为一种化学实体，其在吸收光后会引起另一种化学实体的化学或物理变化。一些光敏剂被用于治疗，如在光动力疗法（PDT）中以及用于癌症诊断（荧光诊断，FD）。PDT已被批准用于多种癌症适应症，FD最近也被批准用于膀胱癌的诊断。所使用的光敏剂在大多数情况下基于卟啉结构。这些光敏剂通常在癌组织中的蓄积程度高于周围组织，并且它们的荧光特性可用于癌症检测。光敏剂可以通过化学合成或由血红素合成中的中间体5-氨基乙酰丙酸（5-ALA）或5-ALA酯内源性诱导产生。治疗效果基于光敏剂被光激活后活性氧（ROS）的形成。单线态氧被认为是对治疗结果最重要的ROS。光敏剂的荧光特性可用于评估其细胞内定位和治疗效果。一些光敏剂在细胞内定位于内吞小泡，在光照后会诱导这些小泡的内容物，包括外部添加的大分子，释放到细胞质中。这是一种名为光化学内化（PCI）的大分子激活新方法的基础。PCI已被证明可增强多种不易穿透质膜的大分子和其他分子的生物活性，包括I型核糖体失活蛋白、免疫毒素、基因编码质粒、腺病毒、肽核酸和化疗药物博来霉素。本文综述了PDT、FD和PCI的背景及现状。
