The amphiphilic and asymmetric structure of porphyrins, when used as photosensitizers (PSs) for photodynamic therapy (PDT), has been shown through numerous previous studies to be a very important property that facilitates their entry into cells, which improves their efficiency in PDT. In this work, two groups of cationic AB3 pyridiniumporphyrins, free-base and chelated with Zn(II), both substituted with alkyl chains of various lengths, were studied in PDT on melanoma cell lines. The aim was to investigate the impact of hydrophilic-lipophilic balance and Zn(II) chelation, and the importance of matching the irradiation wavelength to the optical properties of the PS on in vitro PDT efficiency. Therefore, spectroscopic studies, singlet oxygen production and lipophilicity as well as cellular uptake, localization and cytotoxicity studies of the two series of porphyrins were performed. In both series of porphyrins, the longest alkyl chain (17 C-atoms long) enables the greatest internalization of the PS. Chelation with Zn(II) resulted in better physicochemical properties, but slower cellular internalization. As expected, free-base porphyrins were more PDT efficient than their Zn(II) complexes after 30-min photoactivation by low-fluence (2 mW/cm2) red light (643 nm). However the use of orange light (606 nm) with the same fluence rate was more suitable for Zn(II) porphyrins and resulted in similar overall toxicity to their free-base analogues with similar lipophilicity. Although the highest phototoxicity was achieved with the PSs carrying the longest alkyl chain, TMPyP3-C13H27 and Zn(II)-TMPyP3-C13H27 proved to be the most promising candidates for use in PDT as they exhibit high phototoxicity, but also greater selectivity towards melanoma cell lines (MeWo and A375) compared to fibroblasts (HDF).

中文翻译：

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PDT 中游离碱和 Zn（II） 三离子吡啶卟啉的亲水亲脂平衡和照射波长对黑色素瘤细胞系的影响


卟啉的两亲性和不对称结构，当用作光动力疗法 （PDT） 的光敏剂 （PS） 时，先前的大量研究表明，卟啉是一种非常重要的特性，可促进它们进入细胞，从而提高它们在 PDT 中的效率。在这项工作中，在黑色素瘤细胞系的 PDT 中研究了两组阳离子 AB3 吡啶卟啉，游离碱并与 Zn（II） 螯合，均被不同长度的烷基链取代。目的是研究亲水亲脂平衡和 Zn（II） 螯合的影响，以及将照射波长与 PS 的光学特性相匹配对体外 PDT 效率的重要性。因此，对两个系列卟啉进行了光谱研究、单线态氧产生和亲脂性以及细胞摄取、定位和细胞毒性研究。在这两个系列的卟啉中，最长的烷基链（17 个 C 原子长）能够最大程度地内化 PS。与 Zn（II） 的螯合导致更好的物理化学性质，但细胞内化较慢。正如预期的那样，在低通量 （2 mW/cm2） 红光 （643 nm） 光活化 30 分钟后，游离碱卟啉比其 Zn（II） 配合物更有效。然而，使用具有相同注量速率的橙光 （606 nm） 更适合 Zn（II） 卟啉，并导致与具有相似亲脂性的游离碱类似物具有相似的整体毒性。 尽管携带最长烷基链的 PS 实现了最高的光毒性，但 TMPyP3-C13H27 和 Zn（II）-TMPyP3-C13H27 被证明是用于 PDT 的最有前途的候选者，因为它们表现出高光毒性，但与成纤维细胞 （HDF） 相比，对黑色素瘤细胞系（MeWo 和 A375）的选择性也更高。