The heavy atom effect on thiadiazolo[3,4-g]quinoxaline derivatives as novel photosensitizers for photodynamic therapy

Abstract

Two novel thiadiazolo[3,4-g]quinoxaline (TQ) derivatives, 6,7-bis(4-(hexyloxy)phenyl)-[1,2,5]thiadiazolo[3,4- g]quinoxaline (TQs-1) and 4,9-dibromo-6,7-bis(4-(hexyloxy)phenyl)-[1,2,5]thiadiazolo[3,4-g]quinoxaline (TQs-2) were synthesized and fully characterized by 1H-NMR, 13C-NMR and HR-MS spectra. Their photo-physical and photo-chemical properties, including UV-Vis spectra, fluorescence spectra, photostability and singlet oxygen quantum yield were comprehensively studied. Compared to TQs-1, TQs-2 exhibited a higher singlet oxygen quantum yield and a broader absorption spectrum due to the introduction of two bromine atoms. Furthermore, TQs-2 based nanoparticles (TQs-2 NPs) was obtained via a simple co-assembly strategy using a biocompatible amphiphilic polymer DSPE-mPEG2000 to encapsulate TQs-2. In vitro photodynamic therapy (PDT) experiments to three tumor cells (4T1, MCF-7 and HeLa) and normal cells (L929) were carried out using TQs-2 NPs as photosensitizers. The results showed that TQs-2 NPs possessed negligible dark cytotoxicity to these cells at a high concentration of 50 μg mL-1, but exhibited high light cytotoxicity to them, especially to three tumor cells, under a 532 nm laser illumination at the same concentration, indicating that TQs-2 NPs has a promising potential for PDT applications.