Chan W S, Marshall J F, Svensen R, Bedwell J, Hart I R
Biology of Metastasis Laboratory, Imperial Cancer Research Fund, Lincoln's Inn Fields, London, United Kingdom.
Cancer Res. 1990 Aug 1;50(15):4533-8.
Aluminum sulfonated phthalocyanine has potential as a suitable photosensitizer for use in the photodynamic therapy of cancer. In the present study, cellular uptake and retention of the individual mono-, di-, tri-, and tetrasulfonated derivatives (AlS1-4Pc) were examined in tissue culture and in normal and neoplastic tissue of tumor-bearing mice. Uptake and retention of the various derivatives by cells in tissue culture correlated inversely with the degree of sulfonation. Accordingly, Colo 26 cells in monolayer culture, 24 h after addition of 10 microM of appropriate photosensitizer, had accumulated approximately 25-fold more AlS1Pc than AlS3Pc and retained this species longer than more sulfonated derivatives. In contrast to these in vitro results, it was found that Colo 26 growing s.c. in BALB/c mice accumulated photosensitizer to a greater extent when the degree of sulfonation increased, such that A1S4Pc greater than AlS3Pc greater than AlS2Pc greater than AlS1Pc. By 24-48 h after the i.v. injection of 0.1 ml 2.27 mM solution of individual photosensitizer, the relative ratios of tumor:adjacent tissue varied from greater than 10:1 to greater than 2:1, showing that selective tumor uptake may be affected profoundly by the composition of the phthalocyanine compound. The livers and spleens of both normal and tumor-bearing mice, unlike other normal tissue, took up the sulfonated derivatives in an order that provided a mirror image of that observed in neoplastic tissue. These complex in vivo distribution and retention characteristics appear to be a consequence of relative hydrophilicity/hydrophobicity properties of the sulfonated species and indicate the extent to which these characteristics may influence photosensitizer distribution and accumulation.
磺化酞菁铝有潜力成为适用于癌症光动力疗法的光敏剂。在本研究中，对单个单磺化、二磺化、三磺化和四磺化衍生物（AlS1 - 4Pc）在组织培养以及荷瘤小鼠的正常组织和肿瘤组织中的细胞摄取和滞留情况进行了检测。组织培养中的细胞对各种衍生物的摄取和滞留与磺化程度呈负相关。因此，在单层培养的Colo 26细胞中，添加10微摩尔合适的光敏剂24小时后，积累的AlS1Pc比AlS3Pc多约25倍，并且该物质的滞留时间比磺化程度更高的衍生物更长。与这些体外结果相反，发现在BALB/c小鼠中皮下生长的Colo 26细胞，当磺化程度增加时，光敏剂的积累程度更大，即AlS4Pc＞AlS3Pc＞AlS2Pc＞AlS1Pc。静脉注射0.1毫升2.27毫摩尔单个光敏剂溶液后24 - 48小时，肿瘤与相邻组织的相对比例从大于10:1到大于2:1不等，表明酞菁化合物的组成可能会深刻影响肿瘤的选择性摄取。正常小鼠和荷瘤小鼠的肝脏和脾脏与其他正常组织不同，它们摄取磺化衍生物的顺序与在肿瘤组织中观察到的情况呈镜像关系。这些复杂的体内分布和滞留特征似乎是磺化物质相对亲水性/疏水性的结果，并表明这些特征可能影响光敏剂分布和积累的程度。
