In this study, we present the evaluation in fibroblast cells of photosensitizers semi-synthesized derived from chlorophyll a (as described in literature). The process began with the extraction of methyl-pheophorbide a (1), which was then reacted with primary aliphatic amines (butylamine, hexylamine, and octylamine) to yield molecules 2 to 4. Additionally, purpurin-18 methyl ester (5) was obtained through the oxidation of methyl pheophorbide a (1). By adding different aliphatic amines (butylamine, hexylamine, and octylamine) into the anhydride ring of 5, products 6 to 8 were obtained. Compounds 2-4 and 6-8 exhibited absorption bands around 660nm. The effectiveness of photosensitizers relies on their ability to selectively target damaged cells without harming healthy cells. Therefore, an evaluation of photosensitizers (2- 4, 6-8, and chlorin-e6) against HFF-1 fibroblast cells was performed. Testing two different concentrations (1 and 10μM), it was observed that, under dark conditions, the photosensitizers were primarily non-toxic as they did not significantly reduce cell viability and were close to the control group's viability. Furthermore, the impact of photodynamic therapy (PDT) on cell viability was analyzed by using a light fluence of 30J/cm2. The lower polarity of the compounds (more lipophilic) improved the efficiency of the photosensitizers. In conclusion, this study highlights the successful development of cost-effective photosensitizers with potential applications in PDT. The evaluation against HFF-1 fibroblast cells showed promising results, indicating these photosensitizers could be further investigated for the selective treatment of damaged cells without causing harm to healthy cells.
Photodynamic therapy (PDT) is already a good option for the clinical treatment of several lesions, including mainly nonmelanoma skin cancers. However, cutaneous melanoma treatment remains a challenge when using PDT. One of the reasons for its reduced efficacy is the high pigmentation of melanoma cells. The object of our study is to evaluate the feasibility of the Photodithazine as a photosensitizer for melanoma. Photodithazine is already used in some malignant tumors with satisfactory results and has significant absorption band around 660 nm where the absorption of melanin is low. In this study, we measured the subcellular localization and photodynamic activity of Photodithazine (PDZ) in murine melanoma B16-F10 cell culture. Additionally, a PDT procedure was applied in an animal melanoma model. This first result demonstrates that Photodithazine is more localized at mitochondria in B16F10 cell culture and the cell viability is reduced to less than 90% using 1 µg/mL (PDZ) and 2 J/cm2. We also noticed a rapid PDZ (less than one hour) accumulation in a murine melanoma model. The treatment of melanoma resulted in 20 % more animal survival after one session of PDT compared with the control group. More studies are required to evaluate the cytotoxic effects of Photodithazine at human melanoma.
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