Nitroreductase-responsive photosensitizers for selective imaging and photo-inactivation of intracellular bacteria

Intracellular Staphylococcus aureus (S. aureus), especially the methicillin resistant staphylococcus aureus (MRSA), are difficult to detect and eradicate due to the protection by the host cells. Antibacterial photodynamic therapy (aPDT) offers promise in treating intracellular bacteria, provided that selective damage to the bacteria ranther than host cells can be realized. According to the different nitroreductase (NTR) levels in mammalian cells and S. aureus, herein NTR-responsive photosensitizers (PSs) (T)CyI-NO2 were designed and synthesized. The emission and 1O2 generation of (T)CyI-NO2 are quenched by the 4-nitrobenzyl group, but can be specifically switched on by bacterial NTR. Therefore, selective imaging and photo-inactivation of intracellular S. aureus and MRSA were achieved. Our findings may pave the way for the development of more efficient and selective aPDT agents to combat intractable intracellular infections. Two nitroreductase (NTR)-responsive photosensitizers ((T)CyI-NO2) were designed and synthesized. The quenched fluorescence and singlet oxygen production of (T)CyI-NO2 can be switched on by NTR in S. aureus. Detailed studies displayed TCyI-NO2 was able to selectively image and efficiently photo-inactivate intracellular bacteria with little cytotoxicity. image