Ji Zhenyu, Yang Guanrui, Vasovic Vlada, Cunderlikova Beata, Suo Zhenhe, Nesland Jahn M, Peng Qian
Department of Pathology, The National Hospital-Norwegian Radium Hospital, University of Oslo, Montebello, 0310 Oslo, Norway.
J Photochem Photobiol B. 2006 Sep 1;84(3):213-20. doi: 10.1016/j.jphotobiol.2006.03.006. Epub 2006 May 18.
Photodynamic therapy (PDT) is a combination of light with a lesion-localizing photosensitizer or its precursor to destroy the lesion tissue. PDT has recently become an established modality for several malignant and non-malignant conditions, but it can be further improved through a better understanding of the determinants affecting its therapeutic efficiency. In the present investigation, protoporphyrin IX (PpIX), an efficient photosensitizer either endogenously induced by 5-aminolevulinic acid (ALA) or exogenously administered, was used to correlate its subcellular localization pattern with photodynamic efficiency of human oesophageal carcinoma (KYSE-450, KYSE-70) and normal (Het-1A) cell lines. By means of fluorescence microscopy ALA-induced PpIX was initially localized in the mitochondria, whereas exogenous PpIX was mainly distributed in cell membranes. At a similar amount of cellular PpIX PDT with ALA was significantly more efficient than photodynamic treatment with exogenous PpIX at killing all the 3 cell lines. Measurements of mitochondrial membrane potential and intracellular ATP content, and electron microscopy showed that the mitochondria were initially targeted by ALA-PDT, consistent with intracellular localization pattern of ALA-induced endogenous PpIX. This indicates that subcellular localization pattern of PpIX is an important determinant for its PDT efficiency in the 3 cell lines. Our finding suggests that future new photosensitizers with mitochondrially localizing properties may be designed for effective PDT.
光动力疗法（PDT）是将光与一种能定位病变的光敏剂或其前体相结合，以破坏病变组织。光动力疗法最近已成为治疗多种恶性和非恶性疾病的既定方法，但通过更好地了解影响其治疗效果的决定因素，该疗法仍可进一步改进。在本研究中，原卟啉IX（PpIX），一种由5-氨基酮戊酸（ALA）内源性诱导或外源性给药的高效光敏剂，被用于将其亚细胞定位模式与人类食管癌（KYSE-450、KYSE-70）和正常（Het-1A）细胞系的光动力效率相关联。通过荧光显微镜观察，ALA诱导的PpIX最初定位于线粒体，而外源性PpIX主要分布在细胞膜。在细胞内PpIX含量相似的情况下，ALA介导的光动力疗法在杀死所有这三种细胞系方面显著比外源性PpIX介导的光动力治疗更有效。线粒体膜电位和细胞内ATP含量的测量以及电子显微镜显示，线粒体最初是ALA-PDT的作用靶点，这与ALA诱导的内源性PpIX的细胞内定位模式一致。这表明PpIX的亚细胞定位模式是其在这三种细胞系中光动力效率的重要决定因素。我们的研究结果表明，未来可设计具有线粒体定位特性的新型光敏剂用于有效的光动力疗法。
