Metal complexes hold significant promise in tumor diagnosis and treatment.However,their potential applications in photodynamic therapy(PDT)are hindered by issues such as poor photostability,low yield of reactive oxyge...Metal complexes hold significant promise in tumor diagnosis and treatment.However,their potential applications in photodynamic therapy(PDT)are hindered by issues such as poor photostability,low yield of reactive oxygen species(ROS),and aggregation-induced ROS quenching.To address these challenges,we present a molecular self-assembly strategy utilizing aggregation-induced emission(AIE)conjugates for metal complexes.As a proof of concept,we synthesized a mitochondrial-targeting cyclometalated Ir(Ⅲ)photosensitizer Ir-TPE.This approach significantly enhances the photodynamic effect while mitigating the dark toxicity associated with AIE groups.Ir-TPE readily self-assembles into nanoaggregates in aqueous solution,leading to a significant production of ROS upon light irradiation.Photoirradiated Ir-TPE triggers multiple modes of death by excessively accumulating ROS in the mitochondria,resulting in mitochondrial DNA damage.This damage can lead to ferroptosis and autophagy,two forms of cell death that are highly cytotoxic to cancer cells.The aggregation-enhanced photodynamic effect of Ir-TPE significantly enhances the production of ROS,leading to a more pronounced cytotoxic effect.In vitro and in vivo experiments demonstrate this aggregation-enhanced PDT approach achieves effective in situ tumor eradication.This study not only addresses the limitations of metal complexes in terms of low ROS production due to aggregation but also highlights the potential of this strategy for enhancing ROS production in PDT.展开更多
Considering that hydrogen peroxide(H2O2)plays significant roles in oxidative stress,the cellular signal transduction and essential biological process regulation,the detection and imaging of H2O2 in living systems unde...Considering that hydrogen peroxide(H2O2)plays significant roles in oxidative stress,the cellular signal transduction and essential biological process regulation,the detection and imaging of H2O2 in living systems undertakes critical responsibility.Herein,we have developed a novel two-photon fluorescence turn on probe,named as Pyp-B for mitochondria H2O2 detection in living systems.Selectivity studies show that probe Pyp-B exhibit highly sensitive response toward H2O2 than other reactive oxygen species(ROS)and reactive nitrogen species(RNS)as well as biologically relevant species.The fluorescence colocalization studies demonstrate that the probe can localize in the mitochondria solely.Furthermore,as a bio-compatibility molecule,the highly selective and sensitive of fluorescence probe Pyp-B have been confirmed by its cell imaging application of H2O2 in living A549 cells and zebrafishes under the physiological conditions.展开更多
Mitochondria are a novel and promising therapeutic target for diagnosis, treatment and prevention of a lot of human diseases such as cancer, metabolic diseases and neurodegenerative disease. Owing to the mitochondrial...Mitochondria are a novel and promising therapeutic target for diagnosis, treatment and prevention of a lot of human diseases such as cancer, metabolic diseases and neurodegenerative disease. Owing to the mitochondrial special bilayer structure and highly negative potential nature, therapeutic molecules have multiple difficulties in reaching mitochondria. To overcome multiple barriers for targeting mitochondria, the researchers developed various pharmaceutical preparations such as liposomes, polymeric nanoparticles and inorganic nanoparticles modified by mitochondriotropic moieties like dequalinium (DQA),triphenylphosphonium (TPP), mitochondrial penetrating peptides (MPPs) and mitochondrial protein import machinery that allow specific targeting.The targeted formulations exhibited enhanced pharmacological effect and better therapeutic effect than their untargeted counterpart both in vitro and in vivo. Nanocarriers may be used for bio-therapeutic delivery into specific mitochondria that possess a great potential treatment of mitochondria related diseases.展开更多
Naphthalene,anthracene and pyridone endoperoxides are known to thermally release singlet oxygen.However,in the cycloreversion reaction,singlet oxygen is produced stoichiometrically;therefore,multiple singlet oxygen re...Naphthalene,anthracene and pyridone endoperoxides are known to thermally release singlet oxygen.However,in the cycloreversion reaction,singlet oxygen is produced stoichiometrically;therefore,multiple singlet oxygen releasing modules are expected to be very useful in inducing apoptosis of cancer cells.Herein,we present a potential therapeutic agent presenting three-pyridone endoperoxide modules and a mitochondria targeting group.Compared to previously reported pyridone-based monofunctional endoperoxides,the triple endoperoxide is highly effective as evidenced by assays and fluorescence microscopy.展开更多
Hepatocellular carcinoma is a common and fatal malignancy for which there is no effective systemic therapeutic strategy.Dihydroartemisinin(DHA),a derivative of artemisinin,has been shown to exert anti-tumor effects th...Hepatocellular carcinoma is a common and fatal malignancy for which there is no effective systemic therapeutic strategy.Dihydroartemisinin(DHA),a derivative of artemisinin,has been shown to exert anti-tumor effects through the production of reactive oxygen species(ROS)and resultant mitochondrial damage.However,clinical translation is limited by several drawbacks,such as insolubility,instability and low bioavailability.Here,based on a nanomedicine-based delivery strategy,we fabricated mitochondria-targeted carrier-free nanoparticles coupling DHA and triphenylphosphonium(TPP),aiming to improve bioavailability and mitochondrial targeting.DHA-TPP nanoparticles can be passively delivered to the tumor site by enhanced penetration and retention and then internalized.Flow cytometry and Western blot analysis showed that DHA-TPP nanoparticles increased intracellular ROS,which increased mitochondrial stress and in turn upregulated the downstream Bcl-2 pathway,leading to apoptosis.In vivo experiments showed that DHA-TPP nanoparticles exhibited anti-tumor effects in a mouse model of hepatocellular carcinoma.These findings suggest carrier-free DHA-TPP nanoparticles as a potential therapeutic strategy for hepatocellular carcinoma.展开更多
Photodynamic therapy(PDT)is an effective treatment method for tumors.But the specifically accumulated of photosensitizer was very difficult in the tumor site,which greatly limited the efficacy of PDT.Here,mitochondria...Photodynamic therapy(PDT)is an effective treatment method for tumors.But the specifically accumulated of photosensitizer was very difficult in the tumor site,which greatly limited the efficacy of PDT.Here,mitochondria-targeted Janus mesoporous nanoplatform(JPMO-Pt-CTPP-ZnPc)for PDT was prepared,the nanoplatform has uniform size(275 nm)and good dispersion and biocompatibility.The confocal laser scanning microscopy(CLSM)revealed the signal of ZnPc of JPMO-Pt-CTPP-ZnPc were higher than JPMO-Pt-ZnPc in tumor cells,and flow cytometry results showed the cell uptake efficiency of JPMO-Pt-CTPP-ZnPc was 2.5-fold higher than that of JPMO-Pt-ZnPc.This revealed the modification of CTPP significantly improves the targeting ability of the nanoplatform.In vitro anti-tumor experiment showed the JPMO-Pt-CTPP-ZnPc significantly inhibited the growth of tumor cells upon the irradiation of low-power laser,and the survival rate of cells incubated with 60μg/mL JPMO-Pt-CTPP-ZnPc was only 3%.Simultaneously,compared with JPMO-Pt-ZnPc(not modified with mitochondria targeting molecules CTPP),the PDT efficacy of JPMO-Pt-CTPP-ZnPc was significantly better,as it has targeted mitochondria in cells.展开更多
Well-developed mitochondria-targeted nanocarriers for function regulation are highly desirable.Numerous studies have been conducted on the treatment of mitochondria-related diseases;however,further improvements are re...Well-developed mitochondria-targeted nanocarriers for function regulation are highly desirable.Numerous studies have been conducted on the treatment of mitochondria-related diseases;however,further improvements are required to develop more effective drug delivery methods.Herein,we comprehensively introduce recent developments progress in rational design of mitochondria-targeted nanocarriers,and discuss the different strategies of available nanocarriers for targeting mitochondria.We also highlight the advantages and disadvantages of various carrier systems that are currently in use.Finally,perspective on new generation for mitochondria-targeted delivery systems in the emerging area of drug-based therapeutics is also discussed.展开更多
Hypochlorous acid（HOCl） plays a vital role in many physiological and pathological processes as one of reactive oxygen species（ROS）. Developing highly sensitive and selective methods for HOCl detection is of signif...Hypochlorous acid（HOCl） plays a vital role in many physiological and pathological processes as one of reactive oxygen species（ROS）. Developing highly sensitive and selective methods for HOCl detection is of significant interest. In this work, we developed a benzothiazole based probe 1 for ratiometric fluorescence detection of hypochlorite in living cells. The probe can detect HOCl with high selectivity, fast response（within 30 s） as well as low detection limit（0.18 mmol/L）. Fluorescence co-localization studies demonstrated that probe 1 was a mitochondria-targeted fluorescent probe. Furthermore, confocal fluorescence images of He La cell indicated that probe 1 could be used for monitoring intracellular HOCl in living cells. Finally, test strips experiment suggests that the probe 1 can detect the hypochlorous acid in tap water accompanied by remarkable color change.展开更多
Cancer stem cells(CSCs) are maintained by theirsomatic stem cells and are responsible for tumor initiation, chemoresistance, and metastasis. Evidence for the CSCs existence has been reported for a number of human canc...Cancer stem cells(CSCs) are maintained by theirsomatic stem cells and are responsible for tumor initiation, chemoresistance, and metastasis. Evidence for the CSCs existence has been reported for a number of human cancers. The CSC mitochondria have been shown recently to be an important target for cancer treatment, but clinical significance of CSCs and their mitochondria properties remain unclear. Mitochondriatargeted agents are considerably more effective compared to other agents in triggering apoptosis of CSCs, as well as general cancer cells, via mitochondrial dysfunction. Mitochondrial metabolism is altered in cancer cells because of their reliance on glycolytic intermediates, which are normally destined for oxidative phosphorylation. Therefore, inhibiting cancer-specific modifications in mitochondrial metabolism, increasing reactive oxygen species production, or stimulating mitochondrial permeabilization transition could be promising new therapeutic strategies to activate cell death in CSCs as well, as in general cancer cells. This review analyzed mitochondrial function and its potential as a therapeutic target to induce cell death in CSCs. Furthermore, combined treatment with mitochondriatargeted drugs will be a promising strategy for the treatment of relapsed and refractory cancer.展开更多
Mitochondrial damage is closely related to the occurrence of many diseases.However,accurate monitoring and reporting of mitochondrial damage are not easy.Here,we developed a small molecule fluorescent probe named CB-C...Mitochondrial damage is closely related to the occurrence of many diseases.However,accurate monitoring and reporting of mitochondrial damage are not easy.Here,we developed a small molecule fluorescent probe named CB-Cl,which has splendid spectral properties(large Stokes shift,strong affinity for RNA,etc.)and excellent targeting ability to intracellular mitochondria.After mitochondria were damaged by external stimuli,CB-Cl would light up the nucleolus as a signal reporter.The cascade imaging of mitochondria and nucleolus using CB-Cl can monitor and visualize the mitochondrial status in living cells in real-time.Based on the above advantages,the probe CB-Cl has reference significance for the related research of mitochondrial damage and the prevention and treatment of related diseases.展开更多
Hydrogen peroxide(H2 O2), as important products of oxygen metabolism, plays an important role in many biological processes, such as immune responses and cellular signal transduction. However, abnormal production of H2...Hydrogen peroxide(H2 O2), as important products of oxygen metabolism, plays an important role in many biological processes, such as immune responses and cellular signal transduction. However, abnormal production of H2 O2 can damage cellular biomolecules, which was closely associated with many diseases.Thus, it is urgent to monitor the level change of H2 O2 in living cells, particularly at subcellular levels.Toward this end, a wide variety of H2 O2 fluorescent probes have been designed, developed and applied for imaging of H2 O2 in subcellular levels. In this review, we highlight the representative cases of H2 O2 fluorescent probes with mitochondria, nuclei and lysosomes-targetable ability. The review contains organelle target strategies, structures, fluorescence behavior and biological applications of these probes.展开更多
Formation of Lewy body inclusions（LBs）in the substantia nigra（SN）is a very well-characterized pathological hallmark of Parkinson’s disease（PD）.LBs are aggregates of many biologically inactive proteins including...Formation of Lewy body inclusions（LBs）in the substantia nigra（SN）is a very well-characterized pathological hallmark of Parkinson’s disease（PD）.LBs are aggregates of many biologically inactive proteins including structural elements,alpha-synuclein（asyn）-binding proteins,synphilin-1-binding proteins,and components of the ubiquitin-proteasome system.展开更多
In order to explore the complex interaction between H_(2)S and the development of related diseases,it is urgently necessary to develop effective visualization methods to monitor the dynamic changes of H_(2)S in real t...In order to explore the complex interaction between H_(2)S and the development of related diseases,it is urgently necessary to develop effective visualization methods to monitor the dynamic changes of H_(2)S in real time.Herein,we constructed the NIR fluorescent probe HCy-SSPy based on disulfide cleavage for the rapid imaging of H_(2)S.The hemicyanine(HCy-NH_(2))unit was used as a NIR fluorophore,and asymmetric pyridyl disulfides(SSPy)acted as the specific recognition receptor for H_(2)S.The synthesized HCy-SSPy showed a remarkable NIR turn-on signal at 765 nm activated by H_(2)S.This probe also possessed excellent selectivity and high sensitivity,as well as rapid detection ability for H_(2)S(-5s).Moreover,the low cytotoxicity,mitochondrial localization,and excellent cell imaging performance of HCy-SSPy were discussed.Further biological experiments revealed that the probe not only imaged H_(2)S in tumor-bearing mice but also showed great potential for H_(2)S detection in inflammatory processes.展开更多
基金support from the National Natural Science Foundation of China(Nos.22277056,21977052)the Distinguished Young Scholars of Jiangsu Province(No.BK20230006)+2 种基金the Natural Science Foundation of Jiangsu Province(Nos.BK20230977,BK20231090)the Natural Science Foundation of the Higher Education Institutions of Jiangsu Province(No.23KJB150020)the Jiangsu Excellent Postdoctoral Program(No.2022ZB758)。
文摘Metal complexes hold significant promise in tumor diagnosis and treatment.However,their potential applications in photodynamic therapy(PDT)are hindered by issues such as poor photostability,low yield of reactive oxygen species(ROS),and aggregation-induced ROS quenching.To address these challenges,we present a molecular self-assembly strategy utilizing aggregation-induced emission(AIE)conjugates for metal complexes.As a proof of concept,we synthesized a mitochondrial-targeting cyclometalated Ir(Ⅲ)photosensitizer Ir-TPE.This approach significantly enhances the photodynamic effect while mitigating the dark toxicity associated with AIE groups.Ir-TPE readily self-assembles into nanoaggregates in aqueous solution,leading to a significant production of ROS upon light irradiation.Photoirradiated Ir-TPE triggers multiple modes of death by excessively accumulating ROS in the mitochondria,resulting in mitochondrial DNA damage.This damage can lead to ferroptosis and autophagy,two forms of cell death that are highly cytotoxic to cancer cells.The aggregation-enhanced photodynamic effect of Ir-TPE significantly enhances the production of ROS,leading to a more pronounced cytotoxic effect.In vitro and in vivo experiments demonstrate this aggregation-enhanced PDT approach achieves effective in situ tumor eradication.This study not only addresses the limitations of metal complexes in terms of low ROS production due to aggregation but also highlights the potential of this strategy for enhancing ROS production in PDT.
基金the financial support from the National Natural Science Foundation of China(No.81860630)the China Postdoctoral Science Foundation(No.2019M662968)GuangdongBasic and Applied Basic Research Foundation(Nos.2019A1515110356,2019A1515110877)。
文摘Considering that hydrogen peroxide(H2O2)plays significant roles in oxidative stress,the cellular signal transduction and essential biological process regulation,the detection and imaging of H2O2 in living systems undertakes critical responsibility.Herein,we have developed a novel two-photon fluorescence turn on probe,named as Pyp-B for mitochondria H2O2 detection in living systems.Selectivity studies show that probe Pyp-B exhibit highly sensitive response toward H2O2 than other reactive oxygen species(ROS)and reactive nitrogen species(RNS)as well as biologically relevant species.The fluorescence colocalization studies demonstrate that the probe can localize in the mitochondria solely.Furthermore,as a bio-compatibility molecule,the highly selective and sensitive of fluorescence probe Pyp-B have been confirmed by its cell imaging application of H2O2 in living A549 cells and zebrafishes under the physiological conditions.
基金financially supported by the National Natural Science Foundation of China (Grant No.81473162)the Program for Liaoning Excellent Talents in Universitythe Young and middle-aged career development planning of Shenyang Pharmaceutical University
文摘Mitochondria are a novel and promising therapeutic target for diagnosis, treatment and prevention of a lot of human diseases such as cancer, metabolic diseases and neurodegenerative disease. Owing to the mitochondrial special bilayer structure and highly negative potential nature, therapeutic molecules have multiple difficulties in reaching mitochondria. To overcome multiple barriers for targeting mitochondria, the researchers developed various pharmaceutical preparations such as liposomes, polymeric nanoparticles and inorganic nanoparticles modified by mitochondriotropic moieties like dequalinium (DQA),triphenylphosphonium (TPP), mitochondrial penetrating peptides (MPPs) and mitochondrial protein import machinery that allow specific targeting.The targeted formulations exhibited enhanced pharmacological effect and better therapeutic effect than their untargeted counterpart both in vitro and in vivo. Nanocarriers may be used for bio-therapeutic delivery into specific mitochondria that possess a great potential treatment of mitochondria related diseases.
基金supported by the National Natural Science Foundation of China(22007008,22178048).
文摘Naphthalene,anthracene and pyridone endoperoxides are known to thermally release singlet oxygen.However,in the cycloreversion reaction,singlet oxygen is produced stoichiometrically;therefore,multiple singlet oxygen releasing modules are expected to be very useful in inducing apoptosis of cancer cells.Herein,we present a potential therapeutic agent presenting three-pyridone endoperoxide modules and a mitochondria targeting group.Compared to previously reported pyridone-based monofunctional endoperoxides,the triple endoperoxide is highly effective as evidenced by assays and fluorescence microscopy.
基金funded and supported by the Department of Science and Technology of Guangdong Province(No.2022B1111020005)Key Laboratory of Guangdong Provincial Food and Drug Administration(No.2021ZDB03)+3 种基金the 2020 Guangdong Provincial Science and Technology Innovation Strategy Special Fund(Guangdong-Hong Kong-Macao Joint Lab,No.2020B1212030006)Guangdong Province Universities and Colleges Pearl River Scholar Funded Scheme(No.Guochao Liao,2019)Guangdong Basic and Applied Basic Research Foundation(Nos.2020B1515130005,2022A1515110270,202201011563)The Bureau of Science and Technology of Guangzhou City(No.HMJH_(2)019000)。
文摘Hepatocellular carcinoma is a common and fatal malignancy for which there is no effective systemic therapeutic strategy.Dihydroartemisinin(DHA),a derivative of artemisinin,has been shown to exert anti-tumor effects through the production of reactive oxygen species(ROS)and resultant mitochondrial damage.However,clinical translation is limited by several drawbacks,such as insolubility,instability and low bioavailability.Here,based on a nanomedicine-based delivery strategy,we fabricated mitochondria-targeted carrier-free nanoparticles coupling DHA and triphenylphosphonium(TPP),aiming to improve bioavailability and mitochondrial targeting.DHA-TPP nanoparticles can be passively delivered to the tumor site by enhanced penetration and retention and then internalized.Flow cytometry and Western blot analysis showed that DHA-TPP nanoparticles increased intracellular ROS,which increased mitochondrial stress and in turn upregulated the downstream Bcl-2 pathway,leading to apoptosis.In vivo experiments showed that DHA-TPP nanoparticles exhibited anti-tumor effects in a mouse model of hepatocellular carcinoma.These findings suggest carrier-free DHA-TPP nanoparticles as a potential therapeutic strategy for hepatocellular carcinoma.
基金financial support from the National Natural Science Foundation of China(Nos.81971675,22275099)Project of State Key Laboratory of Organic Electronics and Information Displays,Nanjing University of Posts&Telecommunications(No.GDX2022010014)Natural Science Research Start up Foundation of Recruiting Talents of Nanjing University of Posts and Telecommunications(No.NY222067).
文摘Photodynamic therapy(PDT)is an effective treatment method for tumors.But the specifically accumulated of photosensitizer was very difficult in the tumor site,which greatly limited the efficacy of PDT.Here,mitochondria-targeted Janus mesoporous nanoplatform(JPMO-Pt-CTPP-ZnPc)for PDT was prepared,the nanoplatform has uniform size(275 nm)and good dispersion and biocompatibility.The confocal laser scanning microscopy(CLSM)revealed the signal of ZnPc of JPMO-Pt-CTPP-ZnPc were higher than JPMO-Pt-ZnPc in tumor cells,and flow cytometry results showed the cell uptake efficiency of JPMO-Pt-CTPP-ZnPc was 2.5-fold higher than that of JPMO-Pt-ZnPc.This revealed the modification of CTPP significantly improves the targeting ability of the nanoplatform.In vitro anti-tumor experiment showed the JPMO-Pt-CTPP-ZnPc significantly inhibited the growth of tumor cells upon the irradiation of low-power laser,and the survival rate of cells incubated with 60μg/mL JPMO-Pt-CTPP-ZnPc was only 3%.Simultaneously,compared with JPMO-Pt-ZnPc(not modified with mitochondria targeting molecules CTPP),the PDT efficacy of JPMO-Pt-CTPP-ZnPc was significantly better,as it has targeted mitochondria in cells.
基金financial support from the National Key Research and Development Project (No. 2020YFA0709900)the Key University Science Research Project of Jiangsu Province (No. 19KJA520005)+1 种基金the National Natural Science Foundation of China (No. 22077101)the Open Project Program of State Key Laboratory of Coordination Chemistry (No. 202008)
文摘Well-developed mitochondria-targeted nanocarriers for function regulation are highly desirable.Numerous studies have been conducted on the treatment of mitochondria-related diseases;however,further improvements are required to develop more effective drug delivery methods.Herein,we comprehensively introduce recent developments progress in rational design of mitochondria-targeted nanocarriers,and discuss the different strategies of available nanocarriers for targeting mitochondria.We also highlight the advantages and disadvantages of various carrier systems that are currently in use.Finally,perspective on new generation for mitochondria-targeted delivery systems in the emerging area of drug-based therapeutics is also discussed.
基金supported by the National Natural Science Foundation of China(Nos.21376117,21406109 and 31401588)the Jiangsu Natural Science Funds for Distinguished Young Scholars(No.BK20140043)+1 种基金the Natural Science Foundation of the Jiangsu Higher Education Institutions of China(No.14KJA150005)the Qing Lan Project and the Project of Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD)
文摘Hypochlorous acid（HOCl） plays a vital role in many physiological and pathological processes as one of reactive oxygen species（ROS）. Developing highly sensitive and selective methods for HOCl detection is of significant interest. In this work, we developed a benzothiazole based probe 1 for ratiometric fluorescence detection of hypochlorite in living cells. The probe can detect HOCl with high selectivity, fast response（within 30 s） as well as low detection limit（0.18 mmol/L）. Fluorescence co-localization studies demonstrated that probe 1 was a mitochondria-targeted fluorescent probe. Furthermore, confocal fluorescence images of He La cell indicated that probe 1 could be used for monitoring intracellular HOCl in living cells. Finally, test strips experiment suggests that the probe 1 can detect the hypochlorous acid in tap water accompanied by remarkable color change.
基金Supported by A grant from a Priority Research Centers Program through the National Research Foundation of Korea(NRF)funded by the Ministry of Education,Science and Technology,No.2010-0020224a Basic Science Research Program through the National Research Foundation of Korea(NRF)funded by the Ministry of Education,Science and Technology,No.2012R1A1A2041700
文摘Cancer stem cells(CSCs) are maintained by theirsomatic stem cells and are responsible for tumor initiation, chemoresistance, and metastasis. Evidence for the CSCs existence has been reported for a number of human cancers. The CSC mitochondria have been shown recently to be an important target for cancer treatment, but clinical significance of CSCs and their mitochondria properties remain unclear. Mitochondriatargeted agents are considerably more effective compared to other agents in triggering apoptosis of CSCs, as well as general cancer cells, via mitochondrial dysfunction. Mitochondrial metabolism is altered in cancer cells because of their reliance on glycolytic intermediates, which are normally destined for oxidative phosphorylation. Therefore, inhibiting cancer-specific modifications in mitochondrial metabolism, increasing reactive oxygen species production, or stimulating mitochondrial permeabilization transition could be promising new therapeutic strategies to activate cell death in CSCs as well, as in general cancer cells. This review analyzed mitochondrial function and its potential as a therapeutic target to induce cell death in CSCs. Furthermore, combined treatment with mitochondriatargeted drugs will be a promising strategy for the treatment of relapsed and refractory cancer.
基金the Shenzhen Science and Technology Research and Development Funds(No.JCYJ20190806155409104)National Natural Science Foundation of China(Nos.52150222,21672130 and 52073163)+1 种基金Guangdong Basic and Applied Basic Research Foundation(No.2019A1515110356)the Qilu Young Scholars Program of Shandong University.
文摘Mitochondrial damage is closely related to the occurrence of many diseases.However,accurate monitoring and reporting of mitochondrial damage are not easy.Here,we developed a small molecule fluorescent probe named CB-Cl,which has splendid spectral properties(large Stokes shift,strong affinity for RNA,etc.)and excellent targeting ability to intracellular mitochondria.After mitochondria were damaged by external stimuli,CB-Cl would light up the nucleolus as a signal reporter.The cascade imaging of mitochondria and nucleolus using CB-Cl can monitor and visualize the mitochondrial status in living cells in real-time.Based on the above advantages,the probe CB-Cl has reference significance for the related research of mitochondrial damage and the prevention and treatment of related diseases.
基金the National Natural Science Foundation of China (Nos. 21705102, 21775096)the Shanxi Province Science Foundation for Youths (No. 201701D221061)+1 种基金Shanxi Province Foundation for Returnees (No. 2017-026)Scientific Instrument Center of Shanxi University (No. 201512)
文摘Hydrogen peroxide(H2 O2), as important products of oxygen metabolism, plays an important role in many biological processes, such as immune responses and cellular signal transduction. However, abnormal production of H2 O2 can damage cellular biomolecules, which was closely associated with many diseases.Thus, it is urgent to monitor the level change of H2 O2 in living cells, particularly at subcellular levels.Toward this end, a wide variety of H2 O2 fluorescent probes have been designed, developed and applied for imaging of H2 O2 in subcellular levels. In this review, we highlight the representative cases of H2 O2 fluorescent probes with mitochondria, nuclei and lysosomes-targetable ability. The review contains organelle target strategies, structures, fluorescence behavior and biological applications of these probes.
基金funded by MJ FOX Foundation Rapid Response Innovation Award Grant to AR
文摘Formation of Lewy body inclusions（LBs）in the substantia nigra（SN）is a very well-characterized pathological hallmark of Parkinson’s disease（PD）.LBs are aggregates of many biologically inactive proteins including structural elements,alpha-synuclein（asyn）-binding proteins,synphilin-1-binding proteins,and components of the ubiquitin-proteasome system.
基金supported by the National Natural Science Foundation of China(No.22264013)Hainan Province Science and Technology Special Fund(No.ZDKJ2021038)+1 种基金Key Research and Development Project of Hainan Province(No.ZDYF2025SHFZ043)High-level Talents Project of Hainan Provincial Natural Science Foundation(No.825RC763)。
文摘In order to explore the complex interaction between H_(2)S and the development of related diseases,it is urgently necessary to develop effective visualization methods to monitor the dynamic changes of H_(2)S in real time.Herein,we constructed the NIR fluorescent probe HCy-SSPy based on disulfide cleavage for the rapid imaging of H_(2)S.The hemicyanine(HCy-NH_(2))unit was used as a NIR fluorophore,and asymmetric pyridyl disulfides(SSPy)acted as the specific recognition receptor for H_(2)S.The synthesized HCy-SSPy showed a remarkable NIR turn-on signal at 765 nm activated by H_(2)S.This probe also possessed excellent selectivity and high sensitivity,as well as rapid detection ability for H_(2)S(-5s).Moreover,the low cytotoxicity,mitochondrial localization,and excellent cell imaging performance of HCy-SSPy were discussed.Further biological experiments revealed that the probe not only imaged H_(2)S in tumor-bearing mice but also showed great potential for H_(2)S detection in inflammatory processes.
