The photosensitizer(PS)as photodynamic therapy(PDT)agent,can also serve as the contrast agent for dual-modalffuorescence imaging(FLI)and photoacoustic imaging(PAI)for precise cancer theranostics.In this study,the PAI ...The photosensitizer(PS)as photodynamic therapy(PDT)agent,can also serve as the contrast agent for dual-modalffuorescence imaging(FLI)and photoacoustic imaging(PAI)for precise cancer theranostics.In this study,the PAI capability of commercial PS,benzoporphyrin derivative monoacid ring-A(BPD)were examined and compared with that from the other PSs and dyes such as TPPS_(4),Cy5 dye and ICG.We discovered that BPD exhibited its advantage as contrast agent for PAI.Meanwhile,BPD can also serve as the contrast agent for enhanced FLI.In particular,the PEGylated nanoliposome(PNL)encapsulated BPD(LBPD)was produced for contrast enhanced dual-modal FLI and PAI and imaging-guided high-efficiency PDT.Enhanced FLI and PAI results demonstrated the significant accumulation of LBPD both within and among individual tumor during 24 h monitoring for in vivo experiment tests.In-vitro and in-vivo PDT tests were also performed,which showed that LBPD have higher PDT efficiency and can easily break the blood vessel of tumor tissues as compared to that from BPD.It was discovered that LBPD has great potentials as a diagnosis and treatment agent for dual-modal FLI and PAI-guided PDT of cancer.展开更多
Abnormal accumulation of intracellular and extrac-ellularβ-amyloid(Aβ)aggregates is closely related to the pathogenesis of Alzheimer’s disease(AD).In this work,we use quinolinium derivatives with electron-rich anil...Abnormal accumulation of intracellular and extrac-ellularβ-amyloid(Aβ)aggregates is closely related to the pathogenesis of Alzheimer’s disease(AD).In this work,we use quinolinium derivatives with electron-rich aniline substituents as the skeletons to develop a set of spontaneous blinking ffuorophores by the formation of long-lived radicals.These probes can target Aβ_(1−40) aggregates and exhibit strong deep-red emission upon binding to Aβ_(1−40) aggregates.More importantly,at the single-molecule level,these probes display spontaneous blinking,low duty cycle,and high photon output,which are suitable for the nanoscopic imaging of Aβ aggregates in living cells.The assembly process of the Aβ aggregates was then tracked with nanoscopic imaging.The elongation rate on the cell membrane was noticeably fast over that in the solution.This work provides a feasible strategy for the design of spontaneous blinking ffuorophores for Aβ aggregates.展开更多
The protein Cu/Zn superoxide dismutase (SOD1) isknown to function as a dimer, but its concentration in cells (∼50μM) and the dimerization constant (K_(d) of 500 μM) results suggestthat it exists in a monomer-dimer ...The protein Cu/Zn superoxide dismutase (SOD1) isknown to function as a dimer, but its concentration in cells (∼50μM) and the dimerization constant (K_(d) of 500 μM) results suggestthat it exists in a monomer-dimer equilibrium. It is unclear how theoligomeric state of SOD1 changes when cells are initially exposed tohigh levels of extracellular oxidative stress. To address this problem,we introduced the single-molecule ffuorescence anisotropy (smFA)assay to explore SOD1 oligomeric states in live COS7 cells. smFAspeciffcally probes the ffuorescence polarization changes caused bymolecular rotations where the fast-rotating molecules (either due tosmaller hydrodynamic volume or less viscous environments)deteriorate the emission polarization and thus lower the anisotropy. After validating that smFA is effective in distinguishingmonomeric and dimeric ffuorescence proteins, we overexpressed SOD1 in live COS7 cells and investigated how its oligomeric statechanges under basal, 2 h, and 24 h 100 μM H_(2)O_(2) treatments. We found that treating cells with H_(2)O_(2) promotes SOD1 dimerizationand decreases cellular viscosity in 2 h. Interestingly, prolonged H_(2)O_(2) treatments show similar results as the basal conditions,indicating that cells return to a steady state similar to the basal state after 24 h, despite the presence of H_(2)O_(2). Our resultsdemonstrate that SOD1 changes its oligomeric state equilibrium in response to extracellular oxidative stresses. smFA will open newopportunities to explore the relationship between the SOD1 oligomer state and its H_(2)O_(2)-based signaling and transcription regulationroles.展开更多
基金This work was supported by the National Basic Research Program of China(2015CB352005)the National Natural Science Foundation of China(61705139,61875135,61525503,61620106016,61835009,81727804)+3 种基金Guangdong Natural Science Foundation Innovation Team(2014A030312008,2017A030310136)Shenzhen Basic Research Project(JCYJ20150930104948169,JCYJ20160328144746940,GJHZ20160226202139185,JCYJ20170412105003520,JCYJ20170817094735945,JCYJ20170818090620324)China and Postdoctoral Science Foundation(2017M612724),ChinaThis study was also supported by MYRG2016-00110-FHS and MYRG grants from the University of Macao in Macao,and FDCT 0011/2018/A1 and FDCT 025/2015/A1 grants from Macao government.
文摘The photosensitizer(PS)as photodynamic therapy(PDT)agent,can also serve as the contrast agent for dual-modalffuorescence imaging(FLI)and photoacoustic imaging(PAI)for precise cancer theranostics.In this study,the PAI capability of commercial PS,benzoporphyrin derivative monoacid ring-A(BPD)were examined and compared with that from the other PSs and dyes such as TPPS_(4),Cy5 dye and ICG.We discovered that BPD exhibited its advantage as contrast agent for PAI.Meanwhile,BPD can also serve as the contrast agent for enhanced FLI.In particular,the PEGylated nanoliposome(PNL)encapsulated BPD(LBPD)was produced for contrast enhanced dual-modal FLI and PAI and imaging-guided high-efficiency PDT.Enhanced FLI and PAI results demonstrated the significant accumulation of LBPD both within and among individual tumor during 24 h monitoring for in vivo experiment tests.In-vitro and in-vivo PDT tests were also performed,which showed that LBPD have higher PDT efficiency and can easily break the blood vessel of tumor tissues as compared to that from BPD.It was discovered that LBPD has great potentials as a diagnosis and treatment agent for dual-modal FLI and PAI-guided PDT of cancer.
基金supported by National Natural Science Foundation of China(NSFC,Project No.22174079,21974073)Natural Science Foundation of Hunan Province(2022JJ40266)the Scientific Research Foundation of Hunan Provincial Education Department(20A299).
文摘Abnormal accumulation of intracellular and extrac-ellularβ-amyloid(Aβ)aggregates is closely related to the pathogenesis of Alzheimer’s disease(AD).In this work,we use quinolinium derivatives with electron-rich aniline substituents as the skeletons to develop a set of spontaneous blinking ffuorophores by the formation of long-lived radicals.These probes can target Aβ_(1−40) aggregates and exhibit strong deep-red emission upon binding to Aβ_(1−40) aggregates.More importantly,at the single-molecule level,these probes display spontaneous blinking,low duty cycle,and high photon output,which are suitable for the nanoscopic imaging of Aβ aggregates in living cells.The assembly process of the Aβ aggregates was then tracked with nanoscopic imaging.The elongation rate on the cell membrane was noticeably fast over that in the solution.This work provides a feasible strategy for the design of spontaneous blinking ffuorophores for Aβ aggregates.
基金supported by the National Institutes of Health(Grant No.R35GM133505)and the University of Houston.
文摘The protein Cu/Zn superoxide dismutase (SOD1) isknown to function as a dimer, but its concentration in cells (∼50μM) and the dimerization constant (K_(d) of 500 μM) results suggestthat it exists in a monomer-dimer equilibrium. It is unclear how theoligomeric state of SOD1 changes when cells are initially exposed tohigh levels of extracellular oxidative stress. To address this problem,we introduced the single-molecule ffuorescence anisotropy (smFA)assay to explore SOD1 oligomeric states in live COS7 cells. smFAspeciffcally probes the ffuorescence polarization changes caused bymolecular rotations where the fast-rotating molecules (either due tosmaller hydrodynamic volume or less viscous environments)deteriorate the emission polarization and thus lower the anisotropy. After validating that smFA is effective in distinguishingmonomeric and dimeric ffuorescence proteins, we overexpressed SOD1 in live COS7 cells and investigated how its oligomeric statechanges under basal, 2 h, and 24 h 100 μM H_(2)O_(2) treatments. We found that treating cells with H_(2)O_(2) promotes SOD1 dimerizationand decreases cellular viscosity in 2 h. Interestingly, prolonged H_(2)O_(2) treatments show similar results as the basal conditions,indicating that cells return to a steady state similar to the basal state after 24 h, despite the presence of H_(2)O_(2). Our resultsdemonstrate that SOD1 changes its oligomeric state equilibrium in response to extracellular oxidative stresses. smFA will open newopportunities to explore the relationship between the SOD1 oligomer state and its H_(2)O_(2)-based signaling and transcription regulationroles.
