In vitro evaluation of the photodynamic activity of pyridine-substituted silicon(IV) phthalocyanines against lung cancer

Abstract

In this study, axially disubstituted silicon(IV) phthalocyanines and their water-soluble derivatives, functionalized with pyridine groups, were synthesized. Subsequently, the efficacy of novel water soluble silicon(IV) phthalocyanines (DT-1,3-SiQ and DT-2,3-SiQ) in photodynamic therapy (PDT) for lung cancer was investigated using in vitro methods. The synthesized compounds were characterized using FT-IR, 1H NMR, 13C NMR, and MS techniques, and their photostability properties were evaluated. Following irradiation (0-60 min), DT-1,3-SiQ retained 55 f 4.75% of its stability, whereas DT-2,3-SiQ remained completely stable. DNA-binding studies were performed using UV-Vis spectroscopy and gel electrophoresis assays and both compounds were found to interact with DNA (as evidenced by hypochromism and decreased ct-DNA absorbance and band density). Photonuclease activity toward supercoiled pBR322 plasmid DNA was demonstrated by the increase in Form II DNA as irradiation time increased. Mechanistic studies showed that this activity occurs via singlet oxygen generation through a Type II photochemical mechanism. It was also determined that the BSA band intensity remained unchanged after 30 min of irradiation, indicating that the compounds exhibited a favorable safety profile. Cytotoxic and phototoxic effects on the human lung cancer (A549) cell line were evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Following 30 min of irradiation, it was determined that DT-1,3-SiQ (IC50 value of 0.11 f 0.02 mu M) exhibited higher efficacy compared to the DT-2,3-SiQ (IC50 value of 0.39 f 0.08 mu M). Both compounds exhibited significantly stronger phototoxic effects compared to the positive control, methylene blue (IC50 value of 0.97 f 0.01 mu M). The findings indicate that DT-1,3-SiQ and DT-2,3-SiQ are promising photosensitizers for the treatment of lung cancer. Future research is essential to evaluate their in vivo therapeutic potential and to develop optimized delivery systems for these compounds.