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Zn(II) and free base N-methylated tripyridylporphyrins: impact of solubility and light excitation wavelength on PDT effect

Amphiphilic cationic porphyrins have shown high potential in use as photosensitizers (PSs) for photodynamic therapy (PDT). Our research group has shown that compounds conjugated with long chain (C18) have an exceptional PDT effect compared to hydrophilic analogues on different tested cell lines. Unfortunately, highly effective amphiphilic compounds showed reduced selectivity to tumour cells, relatively high dark toxicity, and their aggregation was observed in high concentration. It must be kept in mind that the optimal ratio of hydrophilic and hydrophobic moieties is necessary to facilitate passage through the membrane bilayer, while maintaining good solubility in water and avoiding formation of aggregates that reduce the PDT effect. Chelation with Zn(II) alters the properties of free base porphyrins ; it changes lipophilicity of the compounds and may increase the lifetime of the excited triplet state (3PS*). The change also occurs in the absorbance spectra, as expected the number of Q bands reduces from four to two and there is a negligible absorption above 610 nm for these compounds to be efficiently activated with red. Therefore, we suggest photoactivation using LED based source of orange light, which better corresponds to the optical properties of Zn(II) porphyrins while maintaining good penetration through the tissue.In this work, we will present the synthesis of two groups of N- methylated tripyridylporphyrins, free base and chelated with Zn(II), both conjugated to alkyl chains of different length. Their photophysical and photochemical properties studied in different solvents, by laser flash photolysis (LFP) and timeresolved fluorescence spectroscopy (TRF) will be presented. The impact of small changes in chain length will also be evaluated in vitro, using MTT assay to detect cytotoxicity and measuring cellular uptake by using fluorescence microscopy on melanoma cells (MeWo) and human foreskin fibroblasts (HFF). To study the effect of the irradiation wavelength, the cytotoxicity of the compounds will be evaluated using red light (645 nm ; fluence rate 2.0 mW / cm2) and orange light (605 nm ; fluence rate 1.5 mW / cm2).

Amphiphilic porphyrins ; Zn(II) chelation ; Photodynamic therapy ; Melanoma

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