Photophysics of Glycosylated Ring-Fused Chlorin Complexes and Their Photosensitizing Effects on Cancer Cells
Photophysics of Glycosylated Ring-Fused Chlorin Complexes and Their Photosensitizing Effects on Cancer Cells
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DOI：
10.1002/cptc.202300028
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发表时间：
2023-06-26
期刊：
影响因子：
3.7
通讯作者：
Lindgren，Mikael
中科院分区：
文献类型：
--
作者：
Hageberg，Ingvild U.;Arja，Katrianne;Lindgren，Mikael
光动力疗法（PDT）作为一种有前途的癌症治疗的未来依赖于开发具有改善的生物物理和生物化学性质的新的选择性和有效的光敏剂（PS）。在此，我们提出了新的糖基化的4，5，6，7-四氢吡唑并[1，5-a]吡啶]融合二氢卟酚剂的合成方法，物理化学性质和光敏化作用，其特征在于葡萄糖，半乳糖或N-乙酰基葡萄糖胺。结果表明，环稳定的甘氨绿素的质子和Zn 2+离子形式都表现出所需的三重激发态和单线态氧生成方面的物理性质，后者在有机溶剂如CHCl 3中超过50%。使用大鼠AY-27和人T24癌细胞模型，发现这些在生物活性方面上级相应的未糖基化二氢卟酚，并且此外，原形式上级Zn稳定化变体2-3倍。对原型进行的初步流式细胞术和细胞定位研究表明，具有坏死和凋亡生物活性，光敏剂定位于线粒体、细胞膜和溶酶体中。然而，定位到溶酶体中是占主导地位的，并且随时间显著增加。我们预计这些发现将有助于开发用于靶向癌症PDT的光敏剂。
The future of photodynamic therapy (PDT) as a promising cancer treatment relies on the development of new selective and effective photosensitizers (PS) with improved photophysical and biochemical qualities. Herein, we present the synthetic procedure, photophysical properties and photosensitizing effects of novel glycosylated 4,5,6,7‐tetrahydropyrazolo[1,5‐a]pyridine] fused chlorin agents featuring either glucose, galactose, or N‐acetyl glucosamine. It is shown that both the proto‐ and Zn2+‐ion forms of the ring‐stabilized glycochlorins exhibit the required photophysical properties in terms of triplet excited states and singlet oxygen generation, the latter more than 50 % in organic solvents such as CHCl3. Employing the rat AY‐27 and human T24 cancer cell models, it was found that these are superior to the corresponding unglycosylated chlorin in biological activity, and moreover, the proto form is 2–3 times superior to the Zn‐stabilized variant. Provisional flow cytometry and cell localization studies of the proto‐form indicate both necrotic and apoptotic biological activity, and that the photosensitizer localizes in the mitochondria, cell membrane and lysosomes. However, the localization into the lysosomes is dominating and increases substantially with time. We anticipate the findings will aid in the development of photosensitizers for targeted cancer PDT.