Anti-cancer and immunomodulatory photodynamic therapy application of novel porphyrin derivatives

Abstract

Breast cancer is a common and fatal disease among women, with treatment options including surgery, chemotherapy, radiotherapy, and photodynamic therapy (PDT). PDT uses photosensitizers to destroy malignant cells. In this study, two new asymmetric porphyrin derivatives, POR1 and POR2, were synthesized. One contains a sulfur atom, while the other has a nitrogen atom. The compounds were characterized using spectroscopic methods. The cytotoxic effects of POR1 and POR2 were evaluated on MDA-MB-231 and MCF-7 breast cancer cell lines. Apoptotic data showed that POR1 increased cell death by 62 % in MCF-7 and 58 % in MDA-MB-231 cells, significantly higher than under dark conditions (less than 40 % for both cell lines). The IC₅₀ values for POR1 and POR2 were 7 μg/mL and 8 μg/mL, respectively, indicating strong cytotoxicity in MCF-7 cells at low concentrations. These effects were observed with and without xenon light exposure, suggesting the potential of POR derivatives as effective PDT agents. The selectivity of the compounds was evaluated on 3T3 fibroblast cells, showing lower cytotoxicity in healthy cells, indicating cancer cell selectivity, especially under light activation. Additionally, the effects of POR1 and POR2 on TNF-α and IL-6 production were studied in Raw 264.7 macrophages to explore their immunomodulatory potential. The Notch1 signaling pathway, relevant to breast cancer and immune response, was also assessed. Our findings suggest that POR1 and POR2 are promising PDT agents with anti-inflammatory and immunomodulatory properties, making them strong candidates for cancer therapy.