Photodynamic therapy(PDT),a light triggered therapeutic mode,has been recognized as an attractive treatment for oncotherapy.The phototoxicity to normal tissues during treatment limited the development of PDT owing to ...Photodynamic therapy(PDT),a light triggered therapeutic mode,has been recognized as an attractive treatment for oncotherapy.The phototoxicity to normal tissues during treatment limited the development of PDT owing to the always“on”properties of photosensitizers.Activatable photosensitizers are of great importance for improving the selectivity of PDT.Herein,we regarded the overexpressed GGT(γ-Glutamyl transpeptidase)enzyme in tumor cells as a biomarker and developed an activatable photosensitizer Cy-GGT by decorating a specific recognition moiety of GGT,L-glutamic acid,to a hemicyanine dye based on photosensitizer Cy-NH_(2).Cy-GGT was in the“off”state with negligible fluorescence and suppressed singlet oxygen generation,but it could be specifically hydrolyzed to Cy-NH_(2) in the presence of GGT,accompanied with significant fluorescence recovery and singlet oxygen generation increase under light irradiation.The in vitro and in vivo studies indicated that Cy-GGT was suitable for precise tumor imaging and could work as an efficient photosensitizer for inhibiting tumor growth.展开更多
Development of new photosensitizers(PSs)with high singlet oxygen quantumyield and minimal side effects is of great interest in photodynamic therapy(PDT).Herein,a facile strategy to significantly improve photosensitiza...Development of new photosensitizers(PSs)with high singlet oxygen quantumyield and minimal side effects is of great interest in photodynamic therapy(PDT).Herein,a facile strategy to significantly improve photosensitization has been demonstrated for the first time with two pentamethine dyes connected by a varying alkyl chain resulting in a series of cyanine dimers.The photophysical properties of the dimerswere studied with steady-state optical spectroscopies,a timecorrelated single photon counting technique,and laser flash photolysis spectrometry.X-ray crystallography confirmed that the molecular packing modes of Cy-Bu-D and Cy-He-D were dominated by H-aggregation.The H-aggregation by dimerization suppresses the radiative singlet decay,which helps to stabilize the highly efficient triplet excitation state.Moreover,the dimers show more intensewavelength absorption in the nearinfrared(ɛ1.5-2.0 times more than monomer Cy-H at 650 nm),better singlet oxygen quantum yield,and a longer triplet-state lifetime than monomer Cy-H,providing excellent performance as a triplet PS.In vivo experiments demonstrated that Cy-He-D successfully suppresses tumor growth after PDT treatment.This work is beneficial to the design of novel heavy atom free PSs for PDT-based theranostic systems.展开更多
基金This work was supported by the National Natural Science Foundation of China(21925802,21878039,21822804,21808028,22022803,22078046)and the Natural Science Foundation of China-Liaoning Joint Fund(U1908202).
文摘Photodynamic therapy(PDT),a light triggered therapeutic mode,has been recognized as an attractive treatment for oncotherapy.The phototoxicity to normal tissues during treatment limited the development of PDT owing to the always“on”properties of photosensitizers.Activatable photosensitizers are of great importance for improving the selectivity of PDT.Herein,we regarded the overexpressed GGT(γ-Glutamyl transpeptidase)enzyme in tumor cells as a biomarker and developed an activatable photosensitizer Cy-GGT by decorating a specific recognition moiety of GGT,L-glutamic acid,to a hemicyanine dye based on photosensitizer Cy-NH_(2).Cy-GGT was in the“off”state with negligible fluorescence and suppressed singlet oxygen generation,but it could be specifically hydrolyzed to Cy-NH_(2) in the presence of GGT,accompanied with significant fluorescence recovery and singlet oxygen generation increase under light irradiation.The in vitro and in vivo studies indicated that Cy-GGT was suitable for precise tumor imaging and could work as an efficient photosensitizer for inhibiting tumor growth.
基金This work was supported by National Natural Science Foundation of China(project 22090011)NSFCLiaoning United Fund(U1908202).
文摘Development of new photosensitizers(PSs)with high singlet oxygen quantumyield and minimal side effects is of great interest in photodynamic therapy(PDT).Herein,a facile strategy to significantly improve photosensitization has been demonstrated for the first time with two pentamethine dyes connected by a varying alkyl chain resulting in a series of cyanine dimers.The photophysical properties of the dimerswere studied with steady-state optical spectroscopies,a timecorrelated single photon counting technique,and laser flash photolysis spectrometry.X-ray crystallography confirmed that the molecular packing modes of Cy-Bu-D and Cy-He-D were dominated by H-aggregation.The H-aggregation by dimerization suppresses the radiative singlet decay,which helps to stabilize the highly efficient triplet excitation state.Moreover,the dimers show more intensewavelength absorption in the nearinfrared(ɛ1.5-2.0 times more than monomer Cy-H at 650 nm),better singlet oxygen quantum yield,and a longer triplet-state lifetime than monomer Cy-H,providing excellent performance as a triplet PS.In vivo experiments demonstrated that Cy-He-D successfully suppresses tumor growth after PDT treatment.This work is beneficial to the design of novel heavy atom free PSs for PDT-based theranostic systems.