Photodynamic activity of meso-substituted cationic pyridyl porphyrin Zn-TOEt4PyP and its non-covalent interaction product with folic acid

Abstract

This study aims to investigate the efficacy of zinc meso-tetra [4-N- (2'-oxyethyl) pyridyl] porphyrin (Zn-TOEt4PyP) and its non-covalent interaction product with folic acid (FA) for targeted Photodynamic therapy (PDT), taking into account the significant overexpression of FA receptors on tumor cells. Liposomal models were employed to demonstrate lipid free radical chain peroxidation induced by photosensitizer (PS) activation, with FA enhancing this effect. PDT effect of PS and its non-covalent interaction product (NCIP) with FA on HeLa cells culture model were analyzed (in vitro) at a maximum density of 3 × 10⁵ cells/well under light exposure. The assessment of the antitumor activity of Zn-TOEt4PyP metalloporphyrin and its NCIP with FA was carried out in vivo on the engrafted solid tumor model of S-180 sarcoma (Croker's sarcoma). Zn-TOEt4PyP, its NCIP with FA, and FA itself led to the successful free radical oxidation of liposomes that were utilized as a model of the lipid bilayer. The interaction product of Zn-TOEt4PyP with FA was active as a cytotoxic agent for HeLa cells. The in vivo study demonstrated the superior efficacy of Zn-TOEt4PyP over its NCIP with FA in tumor reduction. These findings show efficiency of Zn-TOEt4PyP and its NCIP’s with FA for targeted PDT of tumors. Through liposomal, cellular, and animal models, this research provides a comprehensive insight into the efficiency of Zn-TOEt4PyP and NCIP with FA for PDT of tumors in vitro and in vivo. This study holds significant promise for developing novel PDT strategies to improve cancer treatment outcomes.