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Cationic tripyridylporphyrins and their Zn(II) complexes: a comparison of 645 nm with 605 nm light irradiation for PDT

The use of cationic amphiphilic porphyrin-based photosensitisers (PSs) offers many advantages for photodynamic therapy (PDT). In our previous work, cationic tripyridylporphyrins with the long alkyl chain showed an high PDT effect on five different tumour cell lines and on fibroblasts, as opposed to their analogues without the alkyl chain. The increased lipophilicity led to an improved cellular uptake, however, a somewhat dark toxicity was observed as well as a lack of selectivity between normal and cancer cells. This prompted us to investigate the impact of alkyl chains of different length as well as metalation for the fine-tuning of lipophilicity. It was shown with tetrapyridylporphyrins that Zn(II) chelation increases the triplet excited state lifetimes of the porphyrins and also has an effect on their lipophilicity, thus it may improve the PDT activity. Although red light is commonly used for the anti-tumour PDT, orange light also falls under the optimal therapeutic window and may efficiently penetrate skin layers where melanoma occurs. Furthermore, orange light could be more appropriate for photoexcitation of zinc porphyrins given their optical properties. We will present the synthesis of free base N- methylated tripyrid- 3-ylporphyrins with alkyl chains of different length (C8, C10, C16 and C18), and their Zn(II) analogues. Moreover, we will describe and compare their spectroscopic characteristics, lipophilicity, and singlet oxygen production, as well as their PDT activity on human melanoma cells (MeWo) and human foreskin fibroblasts (HFF). We will also compare the PDT activity of Zn(II) complexes after irradiation with orange (605 nm, fluence rate 1.5 mW/cm2, fluence 2.7 J/cm2) and red light (645 nm, fluence rate 2 mW/cm2, fluence 3.6 J/cm2).

Amphiphilic porphyrins ; Zn(II) chelation ; Lipophilicity ; Singlet oxygen production ; Photodynamic therapy

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