FRET-based two-photon benzo[a]phenothiazinium photosensitizer for fluorescence imaging-guided photodynamic therapy

To overcome the conflict between the long-wavelength excitation and high singlet oxygen quantum yield of photosensitizers,we conjugated a two-photon fluorophore,tetrahydroquinoxaline coumarin(TQ),and an efficient photodynamic therapeutic agent,benzo[a]phenothiazinium(NBS-NH_(2)),through a hexamethylene linker to build a two-photon photosensitizer,TQ-NBS.In TQ-NBS,TQ served as an energy donor and NBS-NH_(2) acted as an energy acceptor;and TQ-NBS was a F?rster resonance energy transfer(FRET)cassette with a 92.8%efficiency.The large two-photon absorption cross-section of TQ allowed photosensitizer TQ-NBS to work in a 900 nm two-photon excitation(TPE)mode,which greatly benefited the deep tissue penetration in PDT treatment.Meanwhile,the excellent phototoxicity and near-infrared fluorescence of NBS-NH2was kept in TQ-NBS under a TPE mode via a FRET process.Photosensitizer TQ-NBS exhibited a high phototoxic efficacy in living cells and tumor-bearing mice.