Joint Study on the Development of New PDT Photosensitizers

利用光敏剂治疗癌症的光动力疗法（PDT）得到了广泛的研究。虽然血卟啉衍生物（HpD）已被用于PDT，但它们对波长较长的光（600 nm以上）吸收很少，而这些光具有良好的组织穿透性。本研究合成了不同磺化程度的酞菁锌、ZnTSPc和ZnSPc_<mix>，并比较了它们的肿瘤摄取、蛋白质亲和力和光毒性。用ZnTSPc和ZnSPc_<mix>溶液孵育HeLa细胞。然后除去溶液，用新鲜培养基洗涤细胞，然后加入0.1 N NaOH。ZnSPc_<mix>在680 nm处达到最大值。这表明ZnSPc_<mix>的细胞摄取优于ZnTSPc。结果表明，ZnSPc_<mix>比ZnTSPc更容易在细胞内解离。用含ZnTSPc或ZnSPc_<mix>的F-10培养基孵育后，用DCM染料激光照射HeLa细胞。照射后，台盼蓝甲基化。ZnTSPc的光毒性随辐照能量的降低而降低。相比之下，即使在低染料浓度下，ZnSPc_<mix>也观察到光毒性。虽然染料浓度和辐照能量较低，但ZnSPc_<mix>辐照对HeLa细胞有损伤作用。从以上结果可以看出，ZnSPc_<mix>是比ZnTSPc更好的PDT敏化剂。研究了不同磺化程度的酞菁锌作为PDT增敏剂的性能。从荧光光谱分析来看，ZnSPc_<mix>比ZnTSPc更能融入细胞。ZnSPc_<mix>与血清蛋白的亲和力明显高于ZnTSPc。PDT实验表明，即使在低浓度和低辐照能量下，ZnSPc_<mix>也会对细胞造成损伤。通过扫描电镜观察细胞死亡过程，发现两种化合物对细胞形态的影响存在较大差异。ZnSPc_<mix>的这种行为取决于其疏水性的增加，从而增加了对细胞的渗透。少

Photodynamic therapy (PDT) of cancer utilizing photosensitizers has been widely investigated. Though hematoporphyrin derivatives (HpD) have been used for PDT,they absorb little light of longer wavelengths (above 600 nm) which have good tissue penetration. In this study we synthesized zinc phthalocyanines with different degree of sulfonation, ZnTSPc and ZnSPc_<mix> and compared their tumor uptake, affinity to protein and phototoxicity.HeLa cells were incubated with both ZnTSPc and ZnSPc_<mix> solutions. Solutions were then removed and cells were washed with fresh medium followed by addition of 0.1 N NaOH.The maxima at 680 nm were observed especially in the case of ZnSPc_<mix>. This indicates that cellular uptake of ZnSPc_<mix> was better than that of ZnTSPc. It is concluded that ZnSPc_<mix> is more easily dissociated in cells than ZnTSPc.HeLa cells were irradiated by DCM dye laser after incubation with F-10 medium containing ZnTSPc or ZnSPc_<mix>. After irradiation, the trypan blue meth … More od was carried out. In the case of ZnTSPc, phototoxicity decreased with decreasing irradiation energy. In comparison, the phototoxicity by ZnSPc_<mix> was observed even at low dye concentration. Though the dye concentration and irradiation energy were low, HeLa Cells were damaged by irradiation with ZnSPc_<mix>. From the above results, ZnSPc_<mix> is a better sensitizer for PDT than ZnTSPc.Properties of zinc phthalocyanines sulfonated to difierent degrees were studied as sensitizers for PDT.From the spectrofluorometric analysis, ZnSPc_<mix> was incorporated in cells better than ZnTSPc. It was also clear that the affinity of ZnSPc_<mix> with serum proteins was higher than that of ZnTSPc. PDT experiment showed that cells were damaged by ZnSPc_<mix> even at low concentration and irradiation energy. Observation of the cell-dying process by SEM showed a large difference between cellular morphological changes by both compounds. This behavior of ZnSPc_<mix> depends on the increase of its penetration into cells due to the increase of its hydrophobicity. Less