Photodynamic therapy(PDT),with high spatiotemporal selectivity,minimal side effects and less drug resistance,has emerged as a promising approach for the treatment of cancer.However,inadequate penetration depth and poo...Photodynamic therapy(PDT),with high spatiotemporal selectivity,minimal side effects and less drug resistance,has emerged as a promising approach for the treatment of cancer.However,inadequate penetration depth and poor efficacy seriously restrict its practical application.To address these challenges,we developed a combined therapy platform(RENP@C/D-FA)based on rare-earth-doped nanoparticles(RENPs)with a structure of NaErF_(4):Tm(0.5%)@NaYF_(4),on which photosensitizer Ce6(chlorin e6)and chemo-therapeutic drug(DOX)(doxorubicin)were loaded by encapsulating with an amphiphilic polymer distearoyl phosphatidylethanolamine-polyethylene glycol-folic acid(DSPE-PEG-FA).RENPs with NaErF_(4) as the matrix possess multiple excitation/emission peaks,enabling activation of PDT under near-infrared-Ⅱb(NIR-Ⅱb,1500-1700 nm)excitation and luminescence imaging in NIR-Ⅱb region by absorbing 808 nm near-infrared photons.Furthermore,DOX can be selectively released in the acidic microenvironment of tumors.Benefiting from the tumor targeting capability of folic acid,this platform can successfully ablate tumor cells and inhibit tumor growth by combining PDT and chemotherapy.This innovative approach holds great promise as a powerful tool for cancer treatment,showing the potential to revolutionize PDT.展开更多
The second near-infrared window in a 1500-1700 nm region(known as the NIR-IIb region)presents low autofluorescence and a deep penetration depth,enabling a potential technology for effective imaging and anticounterfeit...The second near-infrared window in a 1500-1700 nm region(known as the NIR-IIb region)presents low autofluorescence and a deep penetration depth,enabling a potential technology for effective imaging and anticounterfeiting applications.However,existing NIR-IIb-emitted fluorescence materials remain limited and possess low luminescent properties.In implementing the enhanced~1525 nm emission of the Er(III)complex in a nonorganic solvent,an amphiphilic diblock copolymer(PEG112-PAA12)was initially synthesized to coordinate with Er(III),and then certain Yb(III)was doped to form the PEG-PAA-Er/Yb complex.The complex shows a dramatic fluorescent enhancement of~250-fold at~1525 nm in D_(2)O than that in H_(2)O under 980-nm laser irradiation,which is ascribed to the following factors:(1)The substitution of H_(2)O by D_(2)O can suppress the quenching effect of H_(2)O at~1470 nm to achieve the emission of PEG-PAA-Er;(2)the doping of Yb(III)enables the co-luminescence effect to PEG-PAA-Er to improve NIR-IIb emission.Notably,the PEG-PAA-Er/Yb complex can construct molecular logic gates with logic functions and optical anticounterfeiting by using the abovementioned fluorescence changes.展开更多
It is of great significance to study the brain structure and function in deep-tissue for neuroscience research and bio-medical applications because of the urgent demand for precise theranostics.Three-photon fluorescen...It is of great significance to study the brain structure and function in deep-tissue for neuroscience research and bio-medical applications because of the urgent demand for precise theranostics.Three-photon fluorescence microscopic(3PFM)bioimaging excited by the light in near-infrared IIb(NIR-IIb,1,500–1,700 nm)spectral region is one of the most promising imaging techniques with the advantages of high spatial resolution,large imaging depth,and reduced scattering.Herein,a type of NIR-IIb light excitable deep-red emissive semiconducting polymer dots(P-dots)with bright 3PF and large three-photon absorption cross-section(σ3)at 1,550 nm was prepared.Then the P-dots were functionalized with polystyrene polymer polystyrene graft ethylene oxide functionalized with carboxyl groups(PS-PEG-COOH)and modified with NH2-poly(ethylene glycol)(PEG)to synthesis photochemically stable and biocompatible P-dots nanoparticles(NPs).Further the P-dots NPs were utilized for in vivo 3PFM bioimaging of cerebral vasculature with and without the brain skull under 1,550 nm femtosecond(fs)laser excitation.In vivo 3PFM bioimaging of the mice cerebral vasculature at various vertical depths was obtained.Moreover,a vivid three-dimensional structure of the mice vascular architecture beneath the skull was reconstructed.At the depth of 350μm beneath the brain skull,3.8μm blood vessels could still be clearly recognized.NIR-IIb excitable P-dots assisted 3PFM bioimaging has great potential in accurate deep tissue bioimaging.展开更多
Drug-induced hepatotoxicity is a long-standing concern of modern medicine.The production of peroxynitrite(ONOO^(-))is proposed as an early sign of the progression of drug-induced hepatotoxicity.However,conventional bl...Drug-induced hepatotoxicity is a long-standing concern of modern medicine.The production of peroxynitrite(ONOO^(-))is proposed as an early sign of the progression of drug-induced hepatotoxicity.However,conventional blood tests fail to offer a real-time unambiguous visualization of such hepatotoxicity in vivo.ONOO^(-)probes that are currently reported are mainly located in the visible or the first near-infrared(NIR-I)window,which have limited in vivo biosensing application due to the autofluorescence and photon scattering.Here,we report an ONOO^(-)responsive cyanine dye,IR-1061 J-aggregate(J_(IR-1061)),which exhibits a red shift over 500 nm,with an absorption peak at 1580 nm in the NIR-IIb region.By conjugating J_(IR-1061) with rare earth nanoparticles(RENPs)that have NIR-IIb emission at 1550 nm,a dual-mode imaging probe RENPs-J_(IR-1061) is developed.RENPs-J_(IR-1061) shows a fast and sensitive response to ONOO^(-),with activatable NIR-IIb fluorescence and a change in the photoacoustic signals,which is successfully applied for real-time monitoring of hepatotoxicity in vivo.展开更多
The long-wavelength region of the near-infrared-IIb(NIR-IIb,1,500–1,700 nm)imaging window has become an ideal window for in vivo imaging due to the suppressed photon scattering and near-zero autofluorescence of biolo...The long-wavelength region of the near-infrared-IIb(NIR-IIb,1,500–1,700 nm)imaging window has become an ideal window for in vivo imaging due to the suppressed photon scattering and near-zero autofluorescence of biological tissues.Therefore,it is necessary to develop fluorescent probes with excellent fluorescence performance and stability for NIR-IIb fluorescence imaging.In this work,zinc-doped silver telluride quantum dots(Zn:Ag_(2)Te QDs)with bright fluorescence in the NIR-IIb window were synthesized.The introduction of Zn dopants inhibited crystal defects and reduced non-radiative transitions.Therefore,the quantum yield and fluorescence lifetime of Zn:Ag_(2)Te QDs were significantly improved.In addition,Zn-doping increased the number of ligands on the surface of QDs,thus enhancing the colloidal stability of Zn:Ag_(2)Te QDs.Moreover,the PEGylated Zn:Ag_(2)Te QDs with high absolute quantum yield realized noninvasive imaging of cerebral vascular of mouse with high resolution able to distinguish blood capillary,which could be utilized to monitor the brain condition of mice after traumatic brain injury.展开更多
Accurate and dynamic visualization of vascular diseases can contribute to restraining further deterioration from diseases in a timely manner.However,visualization is still unable to precisely determine whether and to ...Accurate and dynamic visualization of vascular diseases can contribute to restraining further deterioration from diseases in a timely manner.However,visualization is still unable to precisely determine whether and to what extent blood vessels or brain tissues are damaged.Here,we report novel benzobis(1,2,5-thiadiazole)-based second near-infrared region(NIR-II)fluorophores HY1-HY4 with highly twisted structures(55°at the S_(0) state),extremely strong aggregation-induced emission(AIE)characteristics(I/I_(0)>13),and remarkably high fluorescence quantum yields(QYs)(up to 14.45%)in the NIR-II region(>1000 nm)and∼0.27%in the nearinfrared IIb window(NIR-IIb,>1500 nm)in aqueous solution.Using NIR-IIb AIE HY4 dots,high-resolution NIR-IIb fluorescence imaging of revascularization and thrombolysis,and real-time feedback of the therapeutic efficacy of Chinese medicine Dengzhan Xixin injection(DXI)on ischemic stroke,were achieved for the first time.In addition,results showed that DXI conferred neuroprotection against cerebral ischemia injury mediated via the angiogenesis pathway.These attractive results provide a new perspective for designing ultrabright NIR-IIb probes for vascular-related phenomena,disease assessment,and precise intraoperative imageguided therapy with a deeper tissue penetration depth and higher resolution.展开更多
基金financially supported by the National Natural Science Foundation of China(Nos.22004133 and 22174035)Hubei Province Outstanding Youth Foundation(No.2022CFA082)。
文摘Photodynamic therapy(PDT),with high spatiotemporal selectivity,minimal side effects and less drug resistance,has emerged as a promising approach for the treatment of cancer.However,inadequate penetration depth and poor efficacy seriously restrict its practical application.To address these challenges,we developed a combined therapy platform(RENP@C/D-FA)based on rare-earth-doped nanoparticles(RENPs)with a structure of NaErF_(4):Tm(0.5%)@NaYF_(4),on which photosensitizer Ce6(chlorin e6)and chemo-therapeutic drug(DOX)(doxorubicin)were loaded by encapsulating with an amphiphilic polymer distearoyl phosphatidylethanolamine-polyethylene glycol-folic acid(DSPE-PEG-FA).RENPs with NaErF_(4) as the matrix possess multiple excitation/emission peaks,enabling activation of PDT under near-infrared-Ⅱb(NIR-Ⅱb,1500-1700 nm)excitation and luminescence imaging in NIR-Ⅱb region by absorbing 808 nm near-infrared photons.Furthermore,DOX can be selectively released in the acidic microenvironment of tumors.Benefiting from the tumor targeting capability of folic acid,this platform can successfully ablate tumor cells and inhibit tumor growth by combining PDT and chemotherapy.This innovative approach holds great promise as a powerful tool for cancer treatment,showing the potential to revolutionize PDT.
基金supported by the National Natural Science Foundation of China(Nos.22104056,62288102,and 82302356)Natural Science Foundation of Jiangsu Province(No.BK20210176)+3 种基金2021 JiangSu Shuangchuang(Mass Innovation and Entrepreneurship)Talent Program(No.JSSCBS20210040)the Open Research Fund of State Key Laboratory of Digital Medical Engineering of Southeast University(No.5507059002)the Natural Science Foundation of Fujian Province(No.2023J01529)the innovation team of photoelectric functional materials and devices for biomedical theranostics of Fujian Normal University(No.Y07204080K13).
文摘The second near-infrared window in a 1500-1700 nm region(known as the NIR-IIb region)presents low autofluorescence and a deep penetration depth,enabling a potential technology for effective imaging and anticounterfeiting applications.However,existing NIR-IIb-emitted fluorescence materials remain limited and possess low luminescent properties.In implementing the enhanced~1525 nm emission of the Er(III)complex in a nonorganic solvent,an amphiphilic diblock copolymer(PEG112-PAA12)was initially synthesized to coordinate with Er(III),and then certain Yb(III)was doped to form the PEG-PAA-Er/Yb complex.The complex shows a dramatic fluorescent enhancement of~250-fold at~1525 nm in D_(2)O than that in H_(2)O under 980-nm laser irradiation,which is ascribed to the following factors:(1)The substitution of H_(2)O by D_(2)O can suppress the quenching effect of H_(2)O at~1470 nm to achieve the emission of PEG-PAA-Er;(2)the doping of Yb(III)enables the co-luminescence effect to PEG-PAA-Er to improve NIR-IIb emission.Notably,the PEG-PAA-Er/Yb complex can construct molecular logic gates with logic functions and optical anticounterfeiting by using the abovementioned fluorescence changes.
基金This work was supported by the National Natural Science Foundation of China(Nos.61735016,61975172,and 91632105)Zhejiang Provincial Natural Science Foundation of China(Nos.LR17F050001 and LY17C090005)the Fundamental Research Funds for the Central Universities and State Key Laboratory of Pathogenesis,Prevention and Treatment of High Incidence Diseases in Central Asia Fund(No.SKL-HIDCA-2019-3).
文摘It is of great significance to study the brain structure and function in deep-tissue for neuroscience research and bio-medical applications because of the urgent demand for precise theranostics.Three-photon fluorescence microscopic(3PFM)bioimaging excited by the light in near-infrared IIb(NIR-IIb,1,500–1,700 nm)spectral region is one of the most promising imaging techniques with the advantages of high spatial resolution,large imaging depth,and reduced scattering.Herein,a type of NIR-IIb light excitable deep-red emissive semiconducting polymer dots(P-dots)with bright 3PF and large three-photon absorption cross-section(σ3)at 1,550 nm was prepared.Then the P-dots were functionalized with polystyrene polymer polystyrene graft ethylene oxide functionalized with carboxyl groups(PS-PEG-COOH)and modified with NH2-poly(ethylene glycol)(PEG)to synthesis photochemically stable and biocompatible P-dots nanoparticles(NPs).Further the P-dots NPs were utilized for in vivo 3PFM bioimaging of cerebral vasculature with and without the brain skull under 1,550 nm femtosecond(fs)laser excitation.In vivo 3PFM bioimaging of the mice cerebral vasculature at various vertical depths was obtained.Moreover,a vivid three-dimensional structure of the mice vascular architecture beneath the skull was reconstructed.At the depth of 350μm beneath the brain skull,3.8μm blood vessels could still be clearly recognized.NIR-IIb excitable P-dots assisted 3PFM bioimaging has great potential in accurate deep tissue bioimaging.
基金the National Natural Science Foundation of China,grant number 22374073.
文摘Drug-induced hepatotoxicity is a long-standing concern of modern medicine.The production of peroxynitrite(ONOO^(-))is proposed as an early sign of the progression of drug-induced hepatotoxicity.However,conventional blood tests fail to offer a real-time unambiguous visualization of such hepatotoxicity in vivo.ONOO^(-)probes that are currently reported are mainly located in the visible or the first near-infrared(NIR-I)window,which have limited in vivo biosensing application due to the autofluorescence and photon scattering.Here,we report an ONOO^(-)responsive cyanine dye,IR-1061 J-aggregate(J_(IR-1061)),which exhibits a red shift over 500 nm,with an absorption peak at 1580 nm in the NIR-IIb region.By conjugating J_(IR-1061) with rare earth nanoparticles(RENPs)that have NIR-IIb emission at 1550 nm,a dual-mode imaging probe RENPs-J_(IR-1061) is developed.RENPs-J_(IR-1061) shows a fast and sensitive response to ONOO^(-),with activatable NIR-IIb fluorescence and a change in the photoacoustic signals,which is successfully applied for real-time monitoring of hepatotoxicity in vivo.
基金supported by the National Natural Science Foundation of China(Nos.22174105 and 21974104)the National Key Research and Development(R&D)Program of China(No.2020YFA0908800)Large-scale Instrument and Equipment Sharing Foundation of Wuhan University.
文摘The long-wavelength region of the near-infrared-IIb(NIR-IIb,1,500–1,700 nm)imaging window has become an ideal window for in vivo imaging due to the suppressed photon scattering and near-zero autofluorescence of biological tissues.Therefore,it is necessary to develop fluorescent probes with excellent fluorescence performance and stability for NIR-IIb fluorescence imaging.In this work,zinc-doped silver telluride quantum dots(Zn:Ag_(2)Te QDs)with bright fluorescence in the NIR-IIb window were synthesized.The introduction of Zn dopants inhibited crystal defects and reduced non-radiative transitions.Therefore,the quantum yield and fluorescence lifetime of Zn:Ag_(2)Te QDs were significantly improved.In addition,Zn-doping increased the number of ligands on the surface of QDs,thus enhancing the colloidal stability of Zn:Ag_(2)Te QDs.Moreover,the PEGylated Zn:Ag_(2)Te QDs with high absolute quantum yield realized noninvasive imaging of cerebral vascular of mouse with high resolution able to distinguish blood capillary,which could be utilized to monitor the brain condition of mice after traumatic brain injury.
基金This work was partially supported by grants from the National Key R&D Program of China(no.2020YFA09-08800)NSFC(nos.81773674,81573383,21763002,82111530209,and 91959103)+5 种基金Shenzhen Science and Technology Research Grant(no.JCYJ20190808152019182)Hubei Province Scientific and Technical Innovation Key Project(no.2020BAB058),the Applied Basic Research Program of Wuhan Municipal Bureau of Science and Technology(no.2019020701011429)the Major Science and Technology Project of Sichuan Science and Technology Department(no.2019YFSY0046)Project First-Class Disciplines Development Supported by Chengdu University of Traditional Chinese Medicine(no.CZYJC1903)Tibet Autonomous Region Science and Technology Plan Project Key Project(no.XZ201901-GB-11)the Local Development Funds of Science andTechnology Department of Tibet(nos.XZ202102YD0033C and XZ202001YD0028C),and the Fundamental Research Funds for the Central Universities.
文摘Accurate and dynamic visualization of vascular diseases can contribute to restraining further deterioration from diseases in a timely manner.However,visualization is still unable to precisely determine whether and to what extent blood vessels or brain tissues are damaged.Here,we report novel benzobis(1,2,5-thiadiazole)-based second near-infrared region(NIR-II)fluorophores HY1-HY4 with highly twisted structures(55°at the S_(0) state),extremely strong aggregation-induced emission(AIE)characteristics(I/I_(0)>13),and remarkably high fluorescence quantum yields(QYs)(up to 14.45%)in the NIR-II region(>1000 nm)and∼0.27%in the nearinfrared IIb window(NIR-IIb,>1500 nm)in aqueous solution.Using NIR-IIb AIE HY4 dots,high-resolution NIR-IIb fluorescence imaging of revascularization and thrombolysis,and real-time feedback of the therapeutic efficacy of Chinese medicine Dengzhan Xixin injection(DXI)on ischemic stroke,were achieved for the first time.In addition,results showed that DXI conferred neuroprotection against cerebral ischemia injury mediated via the angiogenesis pathway.These attractive results provide a new perspective for designing ultrabright NIR-IIb probes for vascular-related phenomena,disease assessment,and precise intraoperative imageguided therapy with a deeper tissue penetration depth and higher resolution.
基金supported by the National Natural Science Foundation of China(61705228 and 62105333)the Key Research Program of the Chinese Academy of Sciences(ZDRW-CN-2021-3)Fujian Science&Technology Innovation Laboratory for Optoelectronic Information of China(2020ZZ114)。
