Novel π-extended cationic meso-arylporphyrins as photosensitizers for photodynamic therapy: Synthesis, photoinduced toxicity and in vivofluorescence.

In this work novel cationic π-extended meso-arylporphyrins with increased absorption in the red and near-infrared (NIR) region were synthesized as potential photosensitizers (PS) for photodynamic therapy (PDT). Introduction of two phenylethynyl substituents shifts absorption bands of the porphyrins to the red/NIR region (Q-band up to 689 nm, ε ∼ 60,000 M cm) with high photostability. Zn(II) complexes SI-1 and SI-2 exhibit singlet oxygen quantum yields up to 0.65. The obtained compounds demonstrated an exceptionally high phototoxic effect in nanomolar range (IC50 ∼ 7-60 nM) in the HeLa cell line, which is ∼5-50 times higher compared to the reference chlorin e6. The in vitro intracellular accumulation of compounds was studied using flow cytometry and confocal microscopy. In vivo NIR fluorescence imaging confirms detectability and distinct biodistribution. Compound SI-1 shows the strongest in vivo signal, while SI-4 exhibits the highest dark-to-photoinduced cytotoxicity ratio. The obtained compounds showed great potential as new porphyrin-type photosensitizers.