In this work, we put forward a new and universal approach, i.e., cyanine ketone method, for fabricating meso–aryl heptamethine indocyanines, which is so simple that the treatment of the easy-to-get cyanine ketones wi...In this work, we put forward a new and universal approach, i.e., cyanine ketone method, for fabricating meso–aryl heptamethine indocyanines, which is so simple that the treatment of the easy-to-get cyanine ketones with various aromatic lithium(Ar Li), followed by acidification, could straightforwardly give rise to the products in one-pot way. Importantly, due to the strong nucleophilicity of Ar Li, a series of bulky hydrophilic aromatic groups can be facilely integrated into the meso–position of heptamethine indocyanines, not only effectively inhibiting the undesired dye self-aggregation but also largely improving the water-solubility. Using one of anti-aggregation meso–aryl heptamethine indocyanines, we fabricated a dye-antibody conjugate for in vivo imaging tumor in a mouse model and achieved a high tumor-tonormal tissue ratio. The work laid a chemical foundation for constructing various meso–aryl heptamethine indocyanines, facilitating the advanced imaging and therapeutic applications in future.展开更多
Due to their excellent fluorescence properties and biological function,cyanine dyes have been widely applied in biological imaging.Heptamethine cyanine(Cy7)dyes,as a type of classic near-infrared(NIR)fluorescent dyes,...Due to their excellent fluorescence properties and biological function,cyanine dyes have been widely applied in biological imaging.Heptamethine cyanine(Cy7)dyes,as a type of classic near-infrared(NIR)fluorescent dyes,are considered as one of the effective fluorescent tools in the living organisms due to their good biocompatibility and very low background interference.Bioorthogonal reactions performed in living cells and tissues have developed by leaps and bounds in recent years.The NIR fluorescent labeling technique involving cyanine has attracted widespread attention.This review summarizes their recent application in the field of bioorthogonal imaging,mainly concluding Cy7-type dyes,labeling strategy,bioimaging application,etc.We expect this work can provide some helps for the studies of NIR bioorthogonal reaction in vivo.展开更多
Surface enhanced resonance Raman scattering(SERRS)is a physical phenomenon that occurs when the energy of incident light is dose to that of electronic excitation of reporter molecules(RMs)attached on substrates.SERRS ...Surface enhanced resonance Raman scattering(SERRS)is a physical phenomenon that occurs when the energy of incident light is dose to that of electronic excitation of reporter molecules(RMs)attached on substrates.SERRS has showed great promise in healthcare applications such as tumor diagnosis,image guided tumor surgery and real-time evaluation of therapeutic response due to its ultra-sensitivity,manipulating convenience and easy acessibility.As the most widely used organic near-infrared(NIR)fuorophore,heptamethine cyanines possess the electronic ex-citation energy that is close to the plasmon absorption energy of the gold nano scafolds,which results in the extraordinary enhancement of the SERRS signal.However,the effect of hepta-methine cyanine structure and the gold nanoparticle morphology to the SERRS intensity are barely investigated.This work developed a series of SERRS nanoprobes in which two hepta-methine cyanine derivatives(IR783 and IR780)were used as the RM and three gold nanoparticles(nanorod,nanosphere and nanostar)were used as the substrates.Interestingly,even though IR780 and IR783 possess very similar chemical structure,SERRS signal produced by IR780 was determined as 14 times higher than that of IR783 when the RM concentration was6.5 × 10^(-6) M.In contrast,less than 4.0 fold SERRS signal intensity increase was measured by changing the substrate morphologies.Above experimental results indicate that finely tuning the chemical structure of the heptamethine cyanine could be a feasible way to develop robust SERRS probes to visualize tumor or guide tumor resection with high sensitivity and target to background ratio.展开更多
Fluorophores that exhibit superior photostability have vast applications,ranging from long-term in vivo tracking to cellular super-resolution imaging.Herein,we showcased a promising buffering strategy that significant...Fluorophores that exhibit superior photostability have vast applications,ranging from long-term in vivo tracking to cellular super-resolution imaging.Herein,we showcased a promising buffering strategy that significantly enhanced the photostability of the near-infrared(NIR)emissive heptamethine cyanine(Cy7)by simply employing a water-responsive oxazolidine(Ox)switch to cage the Cy7 scaffold.This switch established an equilibrium between nonfluorescent closed form(CF)and fluorescent open form(OF)isomers that effectively compensated for the loss of OF due to photobleaching.Proven effective in both in vitro and in vivo contexts,this strategy markedly improved the durability and utility of Cy7 for sophisticated imaging techniques,including stable NIR tumor imaging in live mice and mitochondrial super-resolution imaging,thereby paving the way for enhanced bioimaging capabilities even under intense laser irradiation.展开更多
Current phototherapeutic agents based on heptamethine cyanine dyes often rely on symmetric structures,limiting their photodynamic therapy(PDT)efficiency.Herein,we report a novel asymmetric heptamethine cyanine dye(Cyp...Current phototherapeutic agents based on heptamethine cyanine dyes often rely on symmetric structures,limiting their photodynamic therapy(PDT)efficiency.Herein,we report a novel asymmetric heptamethine cyanine dye(Cyp-TPE)that features a twisted tetraphenylethylene moiety.This design facilitates the formation of stable aggregate nanoparticles(NPs)with a cross-arranged structure,as revealed by molecular dynamics simulations.This specific aggregation mode promotes exciton delocalization and dramatically enhances spin-orbit coupling,leading to an unprecedented ROS quantum yield of 154.54%.Under 808 nmlaser irradiation,the Cyp-TPE NPs demonstrate potent synergistic photodynamic and photothermal activity,concurrently triggering ferroptosis and lysosomal dysfunction,thereby achieving multimodal death of cancer cells.Furthermore,the excellent NIR absorption and photothermal conversion of these aggregates enable precise photothermal imaging(PTI)and photoacoustic imaging(PAI).This work highlights the potential of asymmetric molecular design to overcome the limitations of conventional photosensitizers,offering a robust nanoplatform for imaging-guided cancer therapy.展开更多
Heptamethine cyanine dyes,typified by indocyanine green,have been extensively employed as bioimaging indicators and theranostic agents.Significant efforts have been made to develop functional heptamethine cyanine dyes...Heptamethine cyanine dyes,typified by indocyanine green,have been extensively employed as bioimaging indicators and theranostic agents.Significant efforts have been made to develop functional heptamethine cyanine dyes with outstanding bioimaging and theranostic utilities.In this work,we rationally designed and successfully developed a novel indolium-like heptamethine cyanine dye by installing indolium-derived polycyclic aromatic hydrocarbons on the terminal ends of a conjugated polyene backbone.This dye showed excellent photostability and showed bright fluorescent emission in the second near-infrared(NIR-Ⅱ)window with a peak at approximately 1120 nm.Such long wavelength emission prompted a superior bioimaging resolution in vivo.In particular,this NIR-Ⅱ dye had the remarkable capability of marking the blood vessels of the hindlimbs,abdomens,and brains of mice.More significantly,this dye involved a typical indolium-like heptamethine skeleton and exhibited two strong absorption bands in the 700–1300 nm NIR range,which endowed it with an intrinsic tumor-targeting capability and a high photothermal conversion efficiency(up to 68.2%),serving for the photothermal therapy of tumors under the guidance of NIR-Ⅱ fluorescence imaging.This work provides an efficient design strategy for achieving indolium-like heptamethine cyanine dyes with further NIR-Ⅱ emission.展开更多
Our research has identified a couple of near-infrared(NIR)heptamethine indocyanine dyes exhibiting preferential tumor accumnulation property for in vriwo imaging.On the basis of our foregoing work,we describe here a p...Our research has identified a couple of near-infrared(NIR)heptamethine indocyanine dyes exhibiting preferential tumor accumnulation property for in vriwo imaging.On the basis of our foregoing work,we describe here a preliminary structure-activity relationship(SAR)study of 11 related heptamethine indocyanine dyes and several essential requirements of these structures for in vivo tumor-targeted imaging.展开更多
基金supported by National Natural Science Foundation of China (Nos. 22277070, 22274091, 22007061)Youth Talent Support Program of Shanxi Province+1 种基金Program for the Top Young Academic Leaders of Higher Learning Institutions of ShanxiFundamental Research Program of Shanxi Province (No. 20210302123445)。
文摘In this work, we put forward a new and universal approach, i.e., cyanine ketone method, for fabricating meso–aryl heptamethine indocyanines, which is so simple that the treatment of the easy-to-get cyanine ketones with various aromatic lithium(Ar Li), followed by acidification, could straightforwardly give rise to the products in one-pot way. Importantly, due to the strong nucleophilicity of Ar Li, a series of bulky hydrophilic aromatic groups can be facilely integrated into the meso–position of heptamethine indocyanines, not only effectively inhibiting the undesired dye self-aggregation but also largely improving the water-solubility. Using one of anti-aggregation meso–aryl heptamethine indocyanines, we fabricated a dye-antibody conjugate for in vivo imaging tumor in a mouse model and achieved a high tumor-tonormal tissue ratio. The work laid a chemical foundation for constructing various meso–aryl heptamethine indocyanines, facilitating the advanced imaging and therapeutic applications in future.
基金supported by the National Key R&D Program of China(No.2022YFA1207400)National Natural Science Foundation of China(No.22274061)+1 种基金the 111 Project(No.B17019)Fundamental Research Funds for the Central Universities(No.CCNU22QN007).
文摘Due to their excellent fluorescence properties and biological function,cyanine dyes have been widely applied in biological imaging.Heptamethine cyanine(Cy7)dyes,as a type of classic near-infrared(NIR)fluorescent dyes,are considered as one of the effective fluorescent tools in the living organisms due to their good biocompatibility and very low background interference.Bioorthogonal reactions performed in living cells and tissues have developed by leaps and bounds in recent years.The NIR fluorescent labeling technique involving cyanine has attracted widespread attention.This review summarizes their recent application in the field of bioorthogonal imaging,mainly concluding Cy7-type dyes,labeling strategy,bioimaging application,etc.We expect this work can provide some helps for the studies of NIR bioorthogonal reaction in vivo.
基金supported by the National Basic Research Program of China(973 Program,2013CB932500)the National Natural Science Foundation of China(Nos 81371624,81571741)+1 种基金the Nanotechnology Program of Shanghai Science and Technology Committee(13NM1400400,15140901300)The innovation and entrepreneurship training program for college students in Huazhong University of Science&Technology(14A215).Yunfei Zhang and Danqi Li contributed equivalently to this work.
文摘Surface enhanced resonance Raman scattering(SERRS)is a physical phenomenon that occurs when the energy of incident light is dose to that of electronic excitation of reporter molecules(RMs)attached on substrates.SERRS has showed great promise in healthcare applications such as tumor diagnosis,image guided tumor surgery and real-time evaluation of therapeutic response due to its ultra-sensitivity,manipulating convenience and easy acessibility.As the most widely used organic near-infrared(NIR)fuorophore,heptamethine cyanines possess the electronic ex-citation energy that is close to the plasmon absorption energy of the gold nano scafolds,which results in the extraordinary enhancement of the SERRS signal.However,the effect of hepta-methine cyanine structure and the gold nanoparticle morphology to the SERRS intensity are barely investigated.This work developed a series of SERRS nanoprobes in which two hepta-methine cyanine derivatives(IR783 and IR780)were used as the RM and three gold nanoparticles(nanorod,nanosphere and nanostar)were used as the substrates.Interestingly,even though IR780 and IR783 possess very similar chemical structure,SERRS signal produced by IR780 was determined as 14 times higher than that of IR783 when the RM concentration was6.5 × 10^(-6) M.In contrast,less than 4.0 fold SERRS signal intensity increase was measured by changing the substrate morphologies.Above experimental results indicate that finely tuning the chemical structure of the heptamethine cyanine could be a feasible way to develop robust SERRS probes to visualize tumor or guide tumor resection with high sensitivity and target to background ratio.
基金supported by the National Natural Science Foundation of China(grant nos.22225806,22078314,22278394,and 22378385)the Dalian Institute of Chemical Physics,China(grant no.DICPI202142 and DICPI202436)+1 种基金the Ministry of Education,Singapore(grant no.MOE-T2EP10222-0001)Jiangsu Specially Appointed Professorship and the Startup Funding from Nanjing Normal University,China.
文摘Fluorophores that exhibit superior photostability have vast applications,ranging from long-term in vivo tracking to cellular super-resolution imaging.Herein,we showcased a promising buffering strategy that significantly enhanced the photostability of the near-infrared(NIR)emissive heptamethine cyanine(Cy7)by simply employing a water-responsive oxazolidine(Ox)switch to cage the Cy7 scaffold.This switch established an equilibrium between nonfluorescent closed form(CF)and fluorescent open form(OF)isomers that effectively compensated for the loss of OF due to photobleaching.Proven effective in both in vitro and in vivo contexts,this strategy markedly improved the durability and utility of Cy7 for sophisticated imaging techniques,including stable NIR tumor imaging in live mice and mitochondrial super-resolution imaging,thereby paving the way for enhanced bioimaging capabilities even under intense laser irradiation.
基金funded by the National Natural Science Foundation of China(NSFC 82071979).
文摘Current phototherapeutic agents based on heptamethine cyanine dyes often rely on symmetric structures,limiting their photodynamic therapy(PDT)efficiency.Herein,we report a novel asymmetric heptamethine cyanine dye(Cyp-TPE)that features a twisted tetraphenylethylene moiety.This design facilitates the formation of stable aggregate nanoparticles(NPs)with a cross-arranged structure,as revealed by molecular dynamics simulations.This specific aggregation mode promotes exciton delocalization and dramatically enhances spin-orbit coupling,leading to an unprecedented ROS quantum yield of 154.54%.Under 808 nmlaser irradiation,the Cyp-TPE NPs demonstrate potent synergistic photodynamic and photothermal activity,concurrently triggering ferroptosis and lysosomal dysfunction,thereby achieving multimodal death of cancer cells.Furthermore,the excellent NIR absorption and photothermal conversion of these aggregates enable precise photothermal imaging(PTI)and photoacoustic imaging(PAI).This work highlights the potential of asymmetric molecular design to overcome the limitations of conventional photosensitizers,offering a robust nanoplatform for imaging-guided cancer therapy.
基金supported by the National Basic Research Foundation of China(no.2017YFA0505202)financial support from the National Natural Science Foundation of China(nos.21676113 and 21772054)+6 种基金the Distinguished Young Scholar of Hubei Province(no.2018CFA079)the 111 Project B17019the Scholar Support Program of CCNU(no.0900-31101090002)financial support from A*STAR under its Advanced Manufacturing and Engineering Program(no.A2083c0051)the Ministry of Education,Singapore(no.MOE-MOET2EP10120-0007)supported by grants from the 619 National Creative Research Initiative programs of the 620 National Research Foundation of Koreafunded by 621 the Korean government(no.2021R1A6A1A10039823).
文摘Heptamethine cyanine dyes,typified by indocyanine green,have been extensively employed as bioimaging indicators and theranostic agents.Significant efforts have been made to develop functional heptamethine cyanine dyes with outstanding bioimaging and theranostic utilities.In this work,we rationally designed and successfully developed a novel indolium-like heptamethine cyanine dye by installing indolium-derived polycyclic aromatic hydrocarbons on the terminal ends of a conjugated polyene backbone.This dye showed excellent photostability and showed bright fluorescent emission in the second near-infrared(NIR-Ⅱ)window with a peak at approximately 1120 nm.Such long wavelength emission prompted a superior bioimaging resolution in vivo.In particular,this NIR-Ⅱ dye had the remarkable capability of marking the blood vessels of the hindlimbs,abdomens,and brains of mice.More significantly,this dye involved a typical indolium-like heptamethine skeleton and exhibited two strong absorption bands in the 700–1300 nm NIR range,which endowed it with an intrinsic tumor-targeting capability and a high photothermal conversion efficiency(up to 68.2%),serving for the photothermal therapy of tumors under the guidance of NIR-Ⅱ fluorescence imaging.This work provides an efficient design strategy for achieving indolium-like heptamethine cyanine dyes with further NIR-Ⅱ emission.
基金supported by State Key Basic Research Development Program(2012CB518103)Natural Science Foundation Programs(81072523 and 81130026)+1 种基金Chongqing Municipal Natural Sci-ence Foundation Program(CSTC2009BA5043)a program of New Century Excellent Talents in University(NCET)from Ministry of Education to C.S.
文摘Our research has identified a couple of near-infrared(NIR)heptamethine indocyanine dyes exhibiting preferential tumor accumnulation property for in vriwo imaging.On the basis of our foregoing work,we describe here a preliminary structure-activity relationship(SAR)study of 11 related heptamethine indocyanine dyes and several essential requirements of these structures for in vivo tumor-targeted imaging.
