Mitochondria are crucial organelles responsible for maintaining cell growth,and their homeostasis is closely linked to p H regulation.Physiologically,mitochondria exhibit a weakly alkaline state(pH~8.0).However,when s...Mitochondria are crucial organelles responsible for maintaining cell growth,and their homeostasis is closely linked to p H regulation.Physiologically,mitochondria exhibit a weakly alkaline state(pH~8.0).However,when subjected to stress stimuli that cause damage,cells initiate the process of mitophagy,resulting in mitochondrial acidification.Therefore,monitoring changes in mitochondrial p H to comprehend the physiological processes associated with mitophagy is essential.In this study,we developed an asymmetric pentamethine cyanine dye Cy5.5-H-Cy N as a probe for continuous monitoring of mitophagy in living cells.By incorporating an azaindole structure into the dye molecule,a ratiometric fluorescence response was achieved that is specifically responsive to p H variations while preserving its ability to target mitochondria and emit near-infrared fluorescence.Through various methods inducing mitophagy,Cy5.5-H-Cy N was employed to determine mitochondrial p H quantitatively,demonstrating its suitability as an ideal probe for continuous monitoring of mitophagy in living cells.展开更多
Electron transfer is considered to play a critical role in the Type-I photodynamic therapy process,which offers superior performance under hypoxic conditions.However,developing efficient Type-I photosensitizers remain...Electron transfer is considered to play a critical role in the Type-I photodynamic therapy process,which offers superior performance under hypoxic conditions.However,developing efficient Type-I photosensitizers remains challenging because of the competition between energy and electron transfer processes.Therefore,we designed cyanine dyes(Cy-R)with tunable intersystem crossing(ISC)efficiencies,with the ISC rate reaching 9.29×10^(6)s^(−1).Unlike conventional dimers with short-lived charge-separated states,Cy-R aggregates having sufficiently high ISC efficiency undergo symmetry-breaking charge separation(SBCS)in the triplet state,generating long-lived triplet charge-separated species(Cy-R∙+−Cy-R∙−).This mechanism significantly enhances the production of Type-I reactive oxygen species.Furthermore,Cy-Ac self-aggregation facilitated passive tumor targeting and lysosomal accumulation.Upon photoactivation,Cy-Ac induces lysosomal membrane permeabilization,disrupts autophagy,and triggers lysosome-mediated cell death.This study provides a promising strategy for the development of hypoxia-tolerant Type-I photosensitizers via triplet-state SBCS.展开更多
基金supported by the Fundamental Research Funds for the Central Universities(Nos.DUT23YG137 and DUT22LAB601)Liaoning Binhai Laboratory(No.LBLB-202303)+1 种基金Liaoning Province Science and Technology Joint Fund(Nos.2023JH2/101800039 and 2023JH2/101800037)National Natural Science Foundation of China(Nos.21925802,22090011,and 21878039)。
文摘Mitochondria are crucial organelles responsible for maintaining cell growth,and their homeostasis is closely linked to p H regulation.Physiologically,mitochondria exhibit a weakly alkaline state(pH~8.0).However,when subjected to stress stimuli that cause damage,cells initiate the process of mitophagy,resulting in mitochondrial acidification.Therefore,monitoring changes in mitochondrial p H to comprehend the physiological processes associated with mitophagy is essential.In this study,we developed an asymmetric pentamethine cyanine dye Cy5.5-H-Cy N as a probe for continuous monitoring of mitophagy in living cells.By incorporating an azaindole structure into the dye molecule,a ratiometric fluorescence response was achieved that is specifically responsive to p H variations while preserving its ability to target mitochondria and emit near-infrared fluorescence.Through various methods inducing mitophagy,Cy5.5-H-Cy N was employed to determine mitochondrial p H quantitatively,demonstrating its suitability as an ideal probe for continuous monitoring of mitophagy in living cells.
基金supported by the National Natural Science Foundation of China(Project Nos.2478064,22090011,22338005,and 21925802)Science and Technology Innovation Yongjiang 2035(2024Z185)+2 种基金Liaoning Binhai Laboratory(LBLB-2023-03)Liaoning Provincial Science and Technology Joint Fund(2023JH2/101800039 and 2023JH2/101800037)the Fundamental Research Funds for the Central Universities(DUT22LAB601).
文摘Electron transfer is considered to play a critical role in the Type-I photodynamic therapy process,which offers superior performance under hypoxic conditions.However,developing efficient Type-I photosensitizers remains challenging because of the competition between energy and electron transfer processes.Therefore,we designed cyanine dyes(Cy-R)with tunable intersystem crossing(ISC)efficiencies,with the ISC rate reaching 9.29×10^(6)s^(−1).Unlike conventional dimers with short-lived charge-separated states,Cy-R aggregates having sufficiently high ISC efficiency undergo symmetry-breaking charge separation(SBCS)in the triplet state,generating long-lived triplet charge-separated species(Cy-R∙+−Cy-R∙−).This mechanism significantly enhances the production of Type-I reactive oxygen species.Furthermore,Cy-Ac self-aggregation facilitated passive tumor targeting and lysosomal accumulation.Upon photoactivation,Cy-Ac induces lysosomal membrane permeabilization,disrupts autophagy,and triggers lysosome-mediated cell death.This study provides a promising strategy for the development of hypoxia-tolerant Type-I photosensitizers via triplet-state SBCS.
