Slight modification of a G-quadruplex-targeted quinoxaline may boost type-1 photodynamic therapy for triple-negative breast cancer

G-quadruplexes (G4s) are potential drug targets in cancer treatment. However, the G4-targeted ligands seem to be lack of enough selectivity between tumors and normal tissues, appealing for more precise therapeutic strategies. Type-1 photodynamic therapy (PDT) is a promising strategy possessing excellent spatiotemporal precision for solid tumors with hypoxic microenvironment. However, rational design of type-1 photosensitizers that target G4s are never reported. In this study, we designed a novel G4-targeted ligand ( DQ4 ) by introducing an electron-donating piperazine unit into our previously reported quinoxaline scaffold. Such a slight modification significantly eliminated its intrinsic emission, which made DQ4 a promising “turn-on” fluorescent probe for detecting G4s. Moreover, this modification greatly boosted the production of type-1 ROS , enabling DQ4 to be an excellent photosensitizer potentially for treating hypoxic solid tumors. • A novel G4-targeted type-1 photosensitizer was developed by introducing a piperazine unit. • This slight modification made the ligand a “turn-on” fluorescent probe for detecting G4s. • This slight modification greatly boosted the production of type-1 ROS .