Enhanced permeation and retention（EPR） targeting effect of rhodamine B labeled PEG-b-P（LA-co-DHP） [PEG：poly（ethylene glycol）;LA：L-lactide;DHP：2,2-dihydroxylmethyl-propylene carbonate] micelles（RhB-micelles）...Enhanced permeation and retention（EPR） targeting effect of rhodamine B labeled PEG-b-P（LA-co-DHP） [PEG：poly（ethylene glycol）;LA：L-lactide;DHP：2,2-dihydroxylmethyl-propylene carbonate] micelles（RhB-micelles） was observed in H22 liver cancer bearing mice.The RhB-micelles were prepared by conjugating rhodamine B with the DHP units of amphiphilic block copolymer PEG-b-P（LA-co-DHP） followed by subsequent self-assembling of the conjugate.The parent copolymer PEG-b-P（LA-co-DHP） was synthesized by ring-opening copolymerization of LA and DHP with PEG as macroinitiator and diethyl zinc（ZnEt2） as catalyst.The micelles have a spherical shape and the average diameter is ca.50 nm by TEM（transmission electron microscope） or 80 nm by DLS（dynamic light scattering）.Their in vitro cell uptake experiment by CLSM（confocal laser scanning microscopy） and flow cytometry showed preferential internalization of micelles by MCF-7 human breast cancer cells to free RhB.The in vivo tests by live animal imaging and ex vivo excised organ imaging showed that after vena tail injection,free RhB molecules were distributed in the whole body through the circulation system and then gradually metabolized and excreted and there was no preferential partition in tumor bed from the beginning to the end.But the RhB-micelles were preferentially distributed to the tumor bed so that their concentration（fluorescent intensity） in tumor bed got the level of the liver at a certain time point between 1 and 6 h and reached a maximum relative intensity at around 12 h,indicating an obvious EPR effect of RhB-micelles in H22 liver cancer.展开更多
Due to their inherent tunable spectrum,high brightness,excellent biostability and biocompatibility,and functionalization of surfaces,semiconducting polymer dots(Pdots)are now playing an essential role in fluorescent(F...Due to their inherent tunable spectrum,high brightness,excellent biostability and biocompatibility,and functionalization of surfaces,semiconducting polymer dots(Pdots)are now playing an essential role in fluorescent(FL)imaging and disease treatment through bioconjugation with peptides or biomimetic materials.In particular,biomimetic Pdots exhibit their capability in targeted imaging of lesion and increased efficacy for targeting disease treatment.This review will inspect the recent advances in the design and functionalization strategies of biomodified and biomimetic Pdots for enhanced disease detection and therapy.More importantly,the application of these two modifications in targeted FL imaging and cancer treatment is to be addressed in detail.Meanwhile,the main challenges and prospects of biomimetic and biomodified Pdots are to be discussed,which will pave a new avenue for improved disease detection and imaging-guided treatment.展开更多
Objective:Liver cancer is very common in China,with cumulative five-year tumor recurrence rate after a microscopically margin-negative resection of hepatocellular carcinoma up to 70%.Postoperative recurrent hepatocell...Objective:Liver cancer is very common in China,with cumulative five-year tumor recurrence rate after a microscopically margin-negative resection of hepatocellular carcinoma up to 70%.Postoperative recurrent hepatocellular carcinoma presents a challenge for surgeons because of the complexity of postoperative adhesion and the difficulty in of recognizing recurrent lesions.This study aims to introduce a method using an indocyanine green(ICG)fluorescent imaging technique to do repeated laparoscopic liver resection.Method:Patients received repeated laparoscopic liver resection using ICG fluorescent imaging between January 2017 and December 2019 in the Department of General Surgery of Sir Run Run Shaw Hospital were analyzed retrospectively.Basic information,intraoperative information,complications,and followup time were collected and analyzed.Results:Totally,35 patients with a median age of 59 years(ranged 38-82 years)were included.All of the patients received minimally invasive surgery.One case was performed robotically,and only two cases were converted to open surgery due to severe adhesion.The median operating time was 174 minutes,and the median blood loss during surgery was 100 mL.The median hospital stay after surgery was 5 days,with a range of 3e55 days.In total,32(91.4%)patients showed staining by ICG fluorescent imaging,and lesions were visible on fluorescent camera.The median follow-up time was 19.7 months,with a range of 1e40.2 months.The median relapse-free survival time was 18.5 months.Conclusion:Repeated laparoscopic liver resection using ICG fluorescent imaging is a safe and promising approach in the treatment of recurrent liver tumors in selected patients.展开更多
Sulfur dioxide(SO_(2)) and its derivatives have been recognized as harmful environmental pollutants.However,they are often produced during the processing of traditional Chinese medicines,potentially compromising the q...Sulfur dioxide(SO_(2)) and its derivatives have been recognized as harmful environmental pollutants.However,they are often produced during the processing of traditional Chinese medicines,potentially compromising the quality of these medicinal materials and contributing to various health issues.Due to a lack of effective monitoring and imaging tools,the physiological effects of excessive SO_(2) residues in traditional Chinese medicine remain unclear.Therefore,developing a rapid and effective tool for detecting SO_(2) is crucial for understanding its metabolic pathways and effects in vivo.In this study,we developed a near infrared(NIR) and ratiometric fluorescent probe,NIR-RS,which exhibits high sensitivity,selectivity,and rapid response for SO_(2) detection.Notably,NIR-RS accurately quantifies SO_(2) contents in Pinelliae rhizoma(P.rhizoma) samples,with recovery rates from 98.46 % to 102.40 %,and relative standard deviations(RSDs)< 5.0 %.For bioimaging applications,NIR-RS has low cytotoxicity and good mitochondrial-targeting ability,making it suitable for imaging exogenous and endogenous SO_(2) in mitochondria.Additionally,NIR-RS was successfully applied to image SO_(2) content of P.rhizoma samples within cells,revealing that high SO_(2) residue elevated mitochondria adenosine triphosphate(ATP) content,these findings reveal that P.rhizoma with excessive SO_(2) can affect the organism's growth mechanisms through alterations in ATP pathways.In vivo,SO_(2) was found to predominantly accumulate in the liver following gavage with P.rhizoma solution,with accumulation levels increasing in proportion to SO_(2) residue concentration.High SO_(2) concentrations in P.rhizoma can cause pulmonary fibrosis and gastric mucosal damage.This work provides a valuable tool for regulating SO_(2) content in P.rhizoma and may help researcher better understand the metabolism of SO_(2) derivatives and explore their physiological roles in biological systems.展开更多
The fluorophores Xan-OH and Xan-OH/FBS,based on xanthene structure,possess an effective nearinfrared absorption,near-infraredⅡ(NIR-Ⅱ)fluorescent imaging ability,and excellent photothermal property.Xan-OH/FBS also ha...The fluorophores Xan-OH and Xan-OH/FBS,based on xanthene structure,possess an effective nearinfrared absorption,near-infraredⅡ(NIR-Ⅱ)fluorescent imaging ability,and excellent photothermal property.Xan-OH/FBS also has good viscosity-sensitivity,enabling the real-time in vivo visualization of acute liver injury induced by CCl_(4).Moreover,the photothermal conversion coefficient of Xan-OH and Xan-OH/FBS under 808 nm laser irradiation are significant(27.53%and 26.77%,respectively),which could realize NIR-Ⅱfluorescence imaging-guided photothermal therapy for He La xenograft tumor.Given these promising characteristics,Xan-OH/FBS is an efficient NIR-Ⅱfluorescent imaging agent for acute liver injury and a potential photothermal therapeutic agent for tumor.展开更多
The fluorescence imaging (FLI) in the second near-infrared window (NIR-II, 1000–1700nm) has attracted considerable attention in the past decade. In contrast to conventional NIR-I window excitation (808nm/980nm), FLI ...The fluorescence imaging (FLI) in the second near-infrared window (NIR-II, 1000–1700nm) has attracted considerable attention in the past decade. In contrast to conventional NIR-I window excitation (808nm/980nm), FLI with NIR-II window excitation (1064nm/other wavelength beyond 1000nm) can afford deeper tissue penetration depth with high clarity due to the merits of suppressed photon scattering and diminished autofluorescence. In this review, we have summarized NIR-II window excitable/emissive organic/polymeric fluorophores recently developed. The characteristics of these fluorophores such as chemical structures and photophysical properties have also been critically discussed. Furthermore, the latest development of noninvasive in vivo FLI with NIR-II excitation was highlighted. The ideal imaging results emphasized the importance of NIR-II excitation of these fluorophores in enabling deep tissue penetration and high-resolution imaging. Finally, a perspective on the challenges and prospects of NIR-II excitable/emissive organic/polymeric fluorophores was also discussed. We expected this review will be served as a source of inspiration for researchers, stimulating the creation of novel NIR-II excitable fluorophores and fostering the development of bioimaging applications.展开更多
The intricate pathological mechanisms of ischemia-reperfusion injury(IRI)are intimately associated with the imbalance of metabolic substance supply and demand.Investigation of the fluctuated molecules reveals the prog...The intricate pathological mechanisms of ischemia-reperfusion injury(IRI)are intimately associated with the imbalance of metabolic substance supply and demand.Investigation of the fluctuated molecules reveals the progression of reperfusion injury,facilitating earlier diagnosis and treatments.Fluorescence imaging is a powerful technique in fluorescent optical diagnosis,essential for detecting biomarker levels both in vitro and in vivo.By integrating multifunctional scaffolds with specific recognition groups,smallmolecule fluorescent probes(SMFPs)effectively monitor biomarkers related to IRI,providing valuable insights into pathological mechanisms and enhancing early diagnostic capabilities.This review systemically summarizes the recent developments of SMFPs,focusing on design strategies and their applications in the main types of IRI.Furthermore,we discuss the challenges and propose prospects based on existing SMFP applications in this area.We aim to provide a comprehensive analysis of SMFPs for disease diagnosis and inspire researchers to further innovate and develop effective tools for clinical applications.展开更多
The level of glutathione(GSH)is significantly associated with numerous pathological processes,thus,real-time detection of the GSH level is of significance for early diagnosis of GSH-related diseases.Herein,we develope...The level of glutathione(GSH)is significantly associated with numerous pathological processes,thus,real-time detection of the GSH level is of significance for early diagnosis of GSH-related diseases.Herein,we developed in vivo second near-infrared(NIR-II)window fluorescence(FL)and ratiometric photoacoustic(RPA)dual-modality imaging of GSH using a GSH-activatable probe(LET-14).LET-14 was synthesized based on a rhodamine hybrid xanthene skeleton with a FL shielding 2,4-dinitrobenzene sulfonyl group that can be specifically cleaved by GSH,thus resulting in a markedly bathochromic-shift absorption,a 6.5-fold increase in NIR-II FL intensity(FL920)and a 13-fold increase in RPA signal(PA880/PA705)in vitro.Intriguingly,LET-14 exhibits good selectivity and sensitivity for NIR-II FL and RPA dual-modality imaging of GSH in 4T1 tumor-bearing mouse model.Our findings develop an in vivo detection tool of GSH,which has great potential in the field of cancer diagnosis.展开更多
Wide-field mesoscopy provides the capabilities of cortex-wide field of view(FOV),cellular resolution and high frame rate for neuronal imaging in the mouse brain.However,inherent background fluorescence degrades the im...Wide-field mesoscopy provides the capabilities of cortex-wide field of view(FOV),cellular resolution and high frame rate for neuronal imaging in the mouse brain.However,inherent background fluorescence degrades the image quality and hinders neuronal signal extraction.To address this problem,we first introduce a cortex-wide,high-resolution lineillumination mesoscope with a moving slit designed for in vivo mouse brain imaging.This system achieves a 6.6×6.6 mm FOV,microscale cellular resolution,a high frame rate of 10 Hz,as well as the background rejection ability.Furthermore,we integrated patterned illumination into the system to enhance the background suppression.Experimental results show that the proposed system successfully captures neurodynamics in the living mouse brain.Compared with conventional wide-field mesoscopes,the cortex-wide patterned line-illumination mesoscope(PLIM)achieves a threefold increase in the signal-to-background ratio(SBR).With patterned illumination integrated,the SBR enhancement further reaches four-anda-half-fold.展开更多
A simple, water-soluble, Fe3＋-selective fluorescent probe, derived from rhodamine B, was synthesized and characterized. The probe exhibits a fluorescence response toward Fe3＋ with acceptable sensitivity and selectiv...A simple, water-soluble, Fe3＋-selective fluorescent probe, derived from rhodamine B, was synthesized and characterized. The probe exhibits a fluorescence response toward Fe3＋ with acceptable sensitivity and selectivity and even facilitates visual or naked-eye detection of Fe3＋. The experiment results show that the response of the probe to Fe3＋ is pH-independent over a wide range of 4.0-10.0. In addition, fluorescence microscopic imaging experiments have proven that the probe is cell permeable and can be used for monitoring intracellular Fe3＋ in living cells.展开更多
Cysteine(Cys)plays a pivotal role in many physiological and pathological processes,including detoxification and protein synthesis.The abnormal levels of Cys are linked to many diseases.In this study,a novel red-emitti...Cysteine(Cys)plays a pivotal role in many physiological and pathological processes,including detoxification and protein synthesis.The abnormal levels of Cys are linked to many diseases.In this study,a novel red-emitting off-on fluorescent probe Cys-TCF was masterly constructed for discriminative detection of Cys.After a series of experimental assessment,Cys-TCF displayed higher selectivity and sensitivity for Cys over other biothilols with a low detection limit(0.04μmol/L).More notably,the probe was also successfully applied to image Cys in live cells and live zebrafishes with low cytotoxicity.展开更多
Background and Aims:Hepatocellular carcinoma(HCC)is the fourth most common cause of cancer-related death and ranks sixth in terms of incident cases worldwide.The purpose of this study was to develop an effective and s...Background and Aims:Hepatocellular carcinoma(HCC)is the fourth most common cause of cancer-related death and ranks sixth in terms of incident cases worldwide.The purpose of this study was to develop an effective and sensitive method to distinguish liver cancer tissues from normal tissues in HCC patients.Integrinα6 is a promising cell surface target for molecular imaging of HCC,where it is overexpressed and is a prognostic biomarker.We previously identified an integrinα6-targeted peptide CRWYDENAC(RWY)that has been used for positron emission tomography(PET)imaging of HCC in mouse models.Methods:We labeled the integrinα6-targeted RWY peptide with cyanine 7(Cy7)to form an optical probe(Cy7-RWY)for near infrared fluorescent(NIRF)and photoacoustic(PA)imaging in HCC.Mice transplanted with subcutaneous HCC-LM3 or orthotopic HCC-H22 cells that overexpressed integrinα6 were intravenously injected with Cy7-RWY and its corresponding Cy7-control.NIRF and PA images of mice were collected from 0 to 48 h after injection.Results:Both NIRF and PA signals started to accumulate in the tumor 2 h after injection of Cy7-RWY and peaked at 24 h.Conclusions:Cy7-RWY is a promising optical probe for NIRF and PA imaging of HCC in mice,and has potential clinical application for HCC detection.展开更多
A new fluorescent probe（Rhod-Sec） for selenol detection with ultralow background fluorescence have been developed in this paper, which showed a 380-fold off-on fluorescence response, and the nontoxic Rhod-Sec is wel...A new fluorescent probe（Rhod-Sec） for selenol detection with ultralow background fluorescence have been developed in this paper, which showed a 380-fold off-on fluorescence response, and the nontoxic Rhod-Sec is well suitable for detecting and imaging both exogenous and endogenous selenol in living cells. It also can be applied to visualize the fluctuation of selenol in HepG2 cells through LPS-induced cells oxidation resistance.展开更多
A magnetic resonance(MR)-fluorescent dual-mode imaging probe was prepared by conjugating guaiazulene to Gd-DOTA,and used to label human mesenchymal stem cells(hMSCs)via electroporation.The probe self-assembled into na...A magnetic resonance(MR)-fluorescent dual-mode imaging probe was prepared by conjugating guaiazulene to Gd-DOTA,and used to label human mesenchymal stem cells(hMSCs)via electroporation.The probe self-assembled into nanoclusters in the cytoplasm,resulting in a significant reduction in T2-weighted signal intensity that persisted up to 7 days.The fluorescence signal of the probe was observed at 498 nm,and the labelled hMSCs emitted a green fluorescence.The MR-fluorescent dual-mode imaging probe can potentially be used for stem cell tracking in vivo.展开更多
Au or other metal nanostructures have the ability to strongly quench the fluorescence of fluorophores.This feature has made AuNP-conjugates attractive for the construction of platforms for various bioanalytes to overc...Au or other metal nanostructures have the ability to strongly quench the fluorescence of fluorophores.This feature has made AuNP-conjugates attractive for the construction of platforms for various bioanalytes to overcome the limitations of small molecule fluorophores(poor solubility,long reaction time).In this paper,an ultrafast"Turn-On"fluo rescent sensor for biothiols was constructed.The sensor is based on the fluorescent resonance energy transfer(FRET)effect between the fluorophore(PN)and AuNPs,which effectively quenches the fluorescence of the fluorophore.In the presence of thiols,PN is displaced and released from AuNP surfaces,and thus,the fluorescence is rapidly restored.The sensor features appreciable water solubility and ultrafast response time(a few seconds for Cys).In addition,it exhibits high selectivity and a detection limit as low as 12 nmol/L for Hcy.Moreover,the sensor presents good biocompatibility and has been successfully applied for imaging biothiols in living cells.展开更多
A two-photon fluorescent probe TPZn was developed for specific ratiometric imaging Zn2＋ in living cells and tissues. Significant ratiometric fluorescence change was based on photoinduced electron transfer and intramo...A two-photon fluorescent probe TPZn was developed for specific ratiometric imaging Zn2＋ in living cells and tissues. Significant ratiometric fluorescence change was based on photoinduced electron transfer and intramolecular charge transfer. The synthetic method of TPZn was simple. It was successfully used to selectively image Zn2＋ based on the higher binding affinity for Zn2＋ than for Cd2＋. TPZn was easily loaded into the living cell and tissues with high membrane permeability in a complex biological environment. TPZn could clearly visualize endogenous Zn2＋ by TP ratiometric imaging in hippocampal slices at a depth of 120 μm. Thus, TPZn is a useful tool to image of Zn2＋ in living cells and tissues without interference from Cd2＋.展开更多
Combining phototherapy and chemotherapy has been considered a promising modality for cancer therapy due to their synergistic effect.Herein,we developed three D-π-A-structured boron dipyrromethenes(BODIPYs)(named as B...Combining phototherapy and chemotherapy has been considered a promising modality for cancer therapy due to their synergistic effect.Herein,we developed three D-π-A-structured boron dipyrromethenes(BODIPYs)(named as B-B,B-C,and B-C-Pt).Due to their enlargedπ-conjugated structure and high intramolecular charge transfer effect,the synthesized BODIPYs had photothermal conversion capability,and their absorption and fluorescence spectra were red-shifted.The cisplatin-appended BODIPY(B-C-Pt)exhibited good singlet oxygen(^1O_(2))generation ability and near infrared(NIR)absorption and fluorescence(λ_(Abs)=748 nm,λ_(Em)=947 nm).After being encapsulated by distearoyl phosphoethanolamine polyethyleneglycol 2000(DSPE-PEG-2000),which could inhibit the H-aggregation of B-C-Pt,the absorption and fluorescence of the obtained B-C-Pt nanoparticles(NPs)were red-shifted to 762 and 985 nm,respectively.The^1O_(2)quantum yield and photothermal conversion efficiency of the B-C-Pt NPs were 4.0%and 40.6%,respectively.Moreover,B-C-Pt NPs had chemotherapeutic efficacy due to the presence of cisplatin.In vitro and in vivo studies further demonstrated that B-C-Pt NPs had synergistic therapeutic efficacy.Together,B-C-Pt NPs could be employed in NIRⅡfluorescent and photoacoustic imaging-guided synergistic phototherapy and chemotherapy for cancer treatment.展开更多
Fluorescence-based imaging applications have been benefiting greatly from donor-acceptor(D-A)/donor-π-acceptor(D-π-A)fluorescent probes owing to their intramolecular charge transfer(ICT)nature and self-assembly beha...Fluorescence-based imaging applications have been benefiting greatly from donor-acceptor(D-A)/donor-π-acceptor(D-π-A)fluorescent probes owing to their intramolecular charge transfer(ICT)nature and self-assembly behavior.In this study,we design and synthesize a hydrophilic D-A fluorescent probe,namely CHBA,which would self-assemble into interlaced textures down to nanoscale but disassemble by trace amount of water in fingertip area.Upon finger-pressing,it enables fingerprint imaging and covers level-1/2/3 fingerprint information,wherein the sweat pores can be mapped in both bright field model and fluorescence mode,capable of naked-eye-based similarity analysis for personal identity verification(PIV).Spectroscopic analysis and morphology study show that the working mechanism can be attributed to the selective water-erosion effect on the solid-liquid interphase under physical contact.The sweat pore information can be digitized by polar coordinate conversion,further allowing machine-learning-based analysis for PIV application.The final PIV accuracy reaches 100%for all the involved machine-learning models,with no erroneous judgements.A prototype of PIV system is constructed by integrating CHBA with artificial intelligence hardware,wherein the sweat pore imaging,data processing and the decisionmaking could be run in parallel,suggesting high feasibility in real-world application.展开更多
Fluorescent probes have been widely employed in biological imaging and sensing.However,it is always a challenge to design probes with high sensitivity.In this work,based on rhodamine skeleton,we developed a general st...Fluorescent probes have been widely employed in biological imaging and sensing.However,it is always a challenge to design probes with high sensitivity.In this work,based on rhodamine skeleton,we developed a general strategy to construct sensitivity-enhanced fluorescent probe with the help of theoretical calculation for the first time.As a proof of concept,we synthesized a series of HOCl probes.Experiment results showed that with the C-9 of pyronin moiety of rhodamine stabilized by an electron donor group,probe DQF-S exhibited an importantly enhanced sensitivity(LOD:0.2 nmol/L)towards HOCl together with fast response time(<10 s).Moreover,due to the breaking symmetrical electron distribution by another electron donor group,the novel rhodamine probe DQF-S displayed a far red to near-infrared emission(>650 nm)and large Stokes shift.Bioimaging studies indicated that DQF-S can not only effectively detect basal HOCl in various types of cells,but also be successfully applied to image tumor tissue in vivo.These results demonstrate the potential of our design as a useful strategy to develop excellent fluorescent probes for bioimaging.展开更多
Fluorescence litime imaging(FLIM)is an effective noninvasive bioanalytical tol based onmeasuring fuorescent lifetime of fuorophores.A growing number of FLIM studies utilizes ge-netically engineered fluorescent protein...Fluorescence litime imaging(FLIM)is an effective noninvasive bioanalytical tol based onmeasuring fuorescent lifetime of fuorophores.A growing number of FLIM studies utilizes ge-netically engineered fluorescent proteins targeted to specific subcellular structures to probe localmolecular environment,which opens new directions in cell science.This paper highlights theunconventional applications of FLIM for studies of molecular processes in diverse organelles oflive cultured cells.展开更多
基金Supported by the National Basic Research Program of China(No.2009CB930102)the National High Technology Research and Development Program of China(No.2007AA03Z535)+3 种基金the National Natural Science Foundation of China(No.21004062)the China-Japan-Korea Foresight Program(No.20621140369)"100 Talents Program" of the Chinese Academy of Sciences(No.KGCX2- YW-802) the Project of Jilin Provincial Science & Technology Department,China(No.200705110)
文摘Enhanced permeation and retention（EPR） targeting effect of rhodamine B labeled PEG-b-P（LA-co-DHP） [PEG：poly（ethylene glycol）;LA：L-lactide;DHP：2,2-dihydroxylmethyl-propylene carbonate] micelles（RhB-micelles） was observed in H22 liver cancer bearing mice.The RhB-micelles were prepared by conjugating rhodamine B with the DHP units of amphiphilic block copolymer PEG-b-P（LA-co-DHP） followed by subsequent self-assembling of the conjugate.The parent copolymer PEG-b-P（LA-co-DHP） was synthesized by ring-opening copolymerization of LA and DHP with PEG as macroinitiator and diethyl zinc（ZnEt2） as catalyst.The micelles have a spherical shape and the average diameter is ca.50 nm by TEM（transmission electron microscope） or 80 nm by DLS（dynamic light scattering）.Their in vitro cell uptake experiment by CLSM（confocal laser scanning microscopy） and flow cytometry showed preferential internalization of micelles by MCF-7 human breast cancer cells to free RhB.The in vivo tests by live animal imaging and ex vivo excised organ imaging showed that after vena tail injection,free RhB molecules were distributed in the whole body through the circulation system and then gradually metabolized and excreted and there was no preferential partition in tumor bed from the beginning to the end.But the RhB-micelles were preferentially distributed to the tumor bed so that their concentration（fluorescent intensity） in tumor bed got the level of the liver at a certain time point between 1 and 6 h and reached a maximum relative intensity at around 12 h,indicating an obvious EPR effect of RhB-micelles in H22 liver cancer.
基金University of Macao,Grant/Award Numbers:MYRG 2020-00067-FHS,MYRG2019-00082-FHS,MYRG2022-00081-FHSMacao Science and Technology Development Fund,Grant/Award Numbers:FDCT 0011/2018/A1,FDCT 0020/2019/AMJ,FDCT 0048/2021/AGJ+2 种基金Natural Science Foundation of Guangdong ProvinceNational Key R&D Program of China,Grant/Award Number:2019YFE0110400Higher Education Fund of Macao SAR Government,Grant/Award Number:CP-UMAC-2020-01。
文摘Due to their inherent tunable spectrum,high brightness,excellent biostability and biocompatibility,and functionalization of surfaces,semiconducting polymer dots(Pdots)are now playing an essential role in fluorescent(FL)imaging and disease treatment through bioconjugation with peptides or biomimetic materials.In particular,biomimetic Pdots exhibit their capability in targeted imaging of lesion and increased efficacy for targeting disease treatment.This review will inspect the recent advances in the design and functionalization strategies of biomodified and biomimetic Pdots for enhanced disease detection and therapy.More importantly,the application of these two modifications in targeted FL imaging and cancer treatment is to be addressed in detail.Meanwhile,the main challenges and prospects of biomimetic and biomodified Pdots are to be discussed,which will pave a new avenue for improved disease detection and imaging-guided treatment.
基金supported by the National Natural Science Foundation of China(Grant 82072625)Zhejiang Major Medical Science and Technology Plan(Grant WKJ-ZJ-203).
文摘Objective:Liver cancer is very common in China,with cumulative five-year tumor recurrence rate after a microscopically margin-negative resection of hepatocellular carcinoma up to 70%.Postoperative recurrent hepatocellular carcinoma presents a challenge for surgeons because of the complexity of postoperative adhesion and the difficulty in of recognizing recurrent lesions.This study aims to introduce a method using an indocyanine green(ICG)fluorescent imaging technique to do repeated laparoscopic liver resection.Method:Patients received repeated laparoscopic liver resection using ICG fluorescent imaging between January 2017 and December 2019 in the Department of General Surgery of Sir Run Run Shaw Hospital were analyzed retrospectively.Basic information,intraoperative information,complications,and followup time were collected and analyzed.Results:Totally,35 patients with a median age of 59 years(ranged 38-82 years)were included.All of the patients received minimally invasive surgery.One case was performed robotically,and only two cases were converted to open surgery due to severe adhesion.The median operating time was 174 minutes,and the median blood loss during surgery was 100 mL.The median hospital stay after surgery was 5 days,with a range of 3e55 days.In total,32(91.4%)patients showed staining by ICG fluorescent imaging,and lesions were visible on fluorescent camera.The median follow-up time was 19.7 months,with a range of 1e40.2 months.The median relapse-free survival time was 18.5 months.Conclusion:Repeated laparoscopic liver resection using ICG fluorescent imaging is a safe and promising approach in the treatment of recurrent liver tumors in selected patients.
基金supported by the Natural Science Foundation of Hubei Province (Nos.2023AFB376 and 2024AFD287)National Key Research and Development Program (No.2023YFC3503804)the National Natural Science Foundation of China (No.22077044)。
文摘Sulfur dioxide(SO_(2)) and its derivatives have been recognized as harmful environmental pollutants.However,they are often produced during the processing of traditional Chinese medicines,potentially compromising the quality of these medicinal materials and contributing to various health issues.Due to a lack of effective monitoring and imaging tools,the physiological effects of excessive SO_(2) residues in traditional Chinese medicine remain unclear.Therefore,developing a rapid and effective tool for detecting SO_(2) is crucial for understanding its metabolic pathways and effects in vivo.In this study,we developed a near infrared(NIR) and ratiometric fluorescent probe,NIR-RS,which exhibits high sensitivity,selectivity,and rapid response for SO_(2) detection.Notably,NIR-RS accurately quantifies SO_(2) contents in Pinelliae rhizoma(P.rhizoma) samples,with recovery rates from 98.46 % to 102.40 %,and relative standard deviations(RSDs)< 5.0 %.For bioimaging applications,NIR-RS has low cytotoxicity and good mitochondrial-targeting ability,making it suitable for imaging exogenous and endogenous SO_(2) in mitochondria.Additionally,NIR-RS was successfully applied to image SO_(2) content of P.rhizoma samples within cells,revealing that high SO_(2) residue elevated mitochondria adenosine triphosphate(ATP) content,these findings reveal that P.rhizoma with excessive SO_(2) can affect the organism's growth mechanisms through alterations in ATP pathways.In vivo,SO_(2) was found to predominantly accumulate in the liver following gavage with P.rhizoma solution,with accumulation levels increasing in proportion to SO_(2) residue concentration.High SO_(2) concentrations in P.rhizoma can cause pulmonary fibrosis and gastric mucosal damage.This work provides a valuable tool for regulating SO_(2) content in P.rhizoma and may help researcher better understand the metabolism of SO_(2) derivatives and explore their physiological roles in biological systems.
基金supported by the National Natural Science Foundation of China(Nos.22067021,22367024,and 22267023)Innovation Team of Yunnan Education Department+1 种基金the“Youth Talent of Wan Ren Project”the Sichuan Science and Technology Program(No.2022YFS0633)。
文摘The fluorophores Xan-OH and Xan-OH/FBS,based on xanthene structure,possess an effective nearinfrared absorption,near-infraredⅡ(NIR-Ⅱ)fluorescent imaging ability,and excellent photothermal property.Xan-OH/FBS also has good viscosity-sensitivity,enabling the real-time in vivo visualization of acute liver injury induced by CCl_(4).Moreover,the photothermal conversion coefficient of Xan-OH and Xan-OH/FBS under 808 nm laser irradiation are significant(27.53%and 26.77%,respectively),which could realize NIR-Ⅱfluorescence imaging-guided photothermal therapy for He La xenograft tumor.Given these promising characteristics,Xan-OH/FBS is an efficient NIR-Ⅱfluorescent imaging agent for acute liver injury and a potential photothermal therapeutic agent for tumor.
基金supported by the National Nature Science Foundation of China(Nos.62075079,62305127,61975200)the Natural Science Foundation of Jilin Province(20230508135RC)the Science and Technology Development Foundation of Changchun City(23GZZ15).
文摘The fluorescence imaging (FLI) in the second near-infrared window (NIR-II, 1000–1700nm) has attracted considerable attention in the past decade. In contrast to conventional NIR-I window excitation (808nm/980nm), FLI with NIR-II window excitation (1064nm/other wavelength beyond 1000nm) can afford deeper tissue penetration depth with high clarity due to the merits of suppressed photon scattering and diminished autofluorescence. In this review, we have summarized NIR-II window excitable/emissive organic/polymeric fluorophores recently developed. The characteristics of these fluorophores such as chemical structures and photophysical properties have also been critically discussed. Furthermore, the latest development of noninvasive in vivo FLI with NIR-II excitation was highlighted. The ideal imaging results emphasized the importance of NIR-II excitation of these fluorophores in enabling deep tissue penetration and high-resolution imaging. Finally, a perspective on the challenges and prospects of NIR-II excitable/emissive organic/polymeric fluorophores was also discussed. We expected this review will be served as a source of inspiration for researchers, stimulating the creation of novel NIR-II excitable fluorophores and fostering the development of bioimaging applications.
基金financially supported by the National Natural Science Foundation of China(Nos.62288102 and 62475216)Natural Science Foundation of Shaanxi Province(No.2022JM-130)+7 种基金Key Research and Development Program of Shaanxi(No.2024GHZDXM-37)Innovation Capability Support Program of Shaanxi(No.2023-CX-PT-23)Natural Science Basic Research Program of Shaanxi(No.2024JC-YBQN-0919)Fujian Provincial Natural Science Foundation of China(No.2024J01060)National High Level Hospital Clinical Research Funding(No.2023-NHLHCRF-YSPY-01)the Postdoctoral Fellowship Program of CPSF(No.GZC20240889)Innovation Foundation for Doctor Dissertation of Northwestern Polytechnical University(No.CX2023098)Fundamental Research Funds for the Central Universities。
文摘The intricate pathological mechanisms of ischemia-reperfusion injury(IRI)are intimately associated with the imbalance of metabolic substance supply and demand.Investigation of the fluctuated molecules reveals the progression of reperfusion injury,facilitating earlier diagnosis and treatments.Fluorescence imaging is a powerful technique in fluorescent optical diagnosis,essential for detecting biomarker levels both in vitro and in vivo.By integrating multifunctional scaffolds with specific recognition groups,smallmolecule fluorescent probes(SMFPs)effectively monitor biomarkers related to IRI,providing valuable insights into pathological mechanisms and enhancing early diagnostic capabilities.This review systemically summarizes the recent developments of SMFPs,focusing on design strategies and their applications in the main types of IRI.Furthermore,we discuss the challenges and propose prospects based on existing SMFP applications in this area.We aim to provide a comprehensive analysis of SMFPs for disease diagnosis and inspire researchers to further innovate and develop effective tools for clinical applications.
基金supported by the National Natural Science Foundation of China(Nos.82372116,U23A2097)Guangdong Basic and Applied Basic Research Foundation(No.2022A1515010620)+2 种基金Shenzhen Medical Research Fund(Nos.B2302047,A2302047)Shenzhen Science and Technology Program(No.JCYJ20220818095806014)Research Team Cultivation Program of Shenzhen University(No.2023QNT019).
文摘The level of glutathione(GSH)is significantly associated with numerous pathological processes,thus,real-time detection of the GSH level is of significance for early diagnosis of GSH-related diseases.Herein,we developed in vivo second near-infrared(NIR-II)window fluorescence(FL)and ratiometric photoacoustic(RPA)dual-modality imaging of GSH using a GSH-activatable probe(LET-14).LET-14 was synthesized based on a rhodamine hybrid xanthene skeleton with a FL shielding 2,4-dinitrobenzene sulfonyl group that can be specifically cleaved by GSH,thus resulting in a markedly bathochromic-shift absorption,a 6.5-fold increase in NIR-II FL intensity(FL920)and a 13-fold increase in RPA signal(PA880/PA705)in vitro.Intriguingly,LET-14 exhibits good selectivity and sensitivity for NIR-II FL and RPA dual-modality imaging of GSH in 4T1 tumor-bearing mouse model.Our findings develop an in vivo detection tool of GSH,which has great potential in the field of cancer diagnosis.
基金support from the National Natural Science Foundation of China(Grant No.61971256)。
文摘Wide-field mesoscopy provides the capabilities of cortex-wide field of view(FOV),cellular resolution and high frame rate for neuronal imaging in the mouse brain.However,inherent background fluorescence degrades the image quality and hinders neuronal signal extraction.To address this problem,we first introduce a cortex-wide,high-resolution lineillumination mesoscope with a moving slit designed for in vivo mouse brain imaging.This system achieves a 6.6×6.6 mm FOV,microscale cellular resolution,a high frame rate of 10 Hz,as well as the background rejection ability.Furthermore,we integrated patterned illumination into the system to enhance the background suppression.Experimental results show that the proposed system successfully captures neurodynamics in the living mouse brain.Compared with conventional wide-field mesoscopes,the cortex-wide patterned line-illumination mesoscope(PLIM)achieves a threefold increase in the signal-to-background ratio(SBR).With patterned illumination integrated,the SBR enhancement further reaches four-anda-half-fold.
基金supported by Natural Science Foundation of Fujian Province(No.2013H0019)the Science Foundation of Education Department of Fujian Province(No.JA11064)+1 种基金the Open Foundation of the State Key Laboratory of Fine Chemicals(No.KF1307)the Open Foundation of Ministry of Education Key Laboratory of Synthetic and Natural Functional Molecular Chemistry
文摘A simple, water-soluble, Fe3＋-selective fluorescent probe, derived from rhodamine B, was synthesized and characterized. The probe exhibits a fluorescence response toward Fe3＋ with acceptable sensitivity and selectivity and even facilitates visual or naked-eye detection of Fe3＋. The experiment results show that the response of the probe to Fe3＋ is pH-independent over a wide range of 4.0-10.0. In addition, fluorescence microscopic imaging experiments have proven that the probe is cell permeable and can be used for monitoring intracellular Fe3＋ in living cells.
基金financial supports from the National Natural Science Foundation of China (Nos.21708017,21572093,21778028)Lanzhou University (the Fundamental Research Funds for the Central Universities,No.lzujbky-2018-64)Natural Science Foundation of Gansu Province (No.17JR5RA193)
文摘Cysteine(Cys)plays a pivotal role in many physiological and pathological processes,including detoxification and protein synthesis.The abnormal levels of Cys are linked to many diseases.In this study,a novel red-emitting off-on fluorescent probe Cys-TCF was masterly constructed for discriminative detection of Cys.After a series of experimental assessment,Cys-TCF displayed higher selectivity and sensitivity for Cys over other biothilols with a low detection limit(0.04μmol/L).More notably,the probe was also successfully applied to image Cys in live cells and live zebrafishes with low cytotoxicity.
基金funded by the National Natural Science Foundation of China (Grant:81972531)Fundamental Research Funds for the Central Universities (Grant:19ykpy174)+1 种基金GuangDong Basic and Applied Basic Research Foundation (Grant:2020A1515011374)GuangDong Basic and Applied Basic Research Foundation (Grant:202102020138).
文摘Background and Aims:Hepatocellular carcinoma(HCC)is the fourth most common cause of cancer-related death and ranks sixth in terms of incident cases worldwide.The purpose of this study was to develop an effective and sensitive method to distinguish liver cancer tissues from normal tissues in HCC patients.Integrinα6 is a promising cell surface target for molecular imaging of HCC,where it is overexpressed and is a prognostic biomarker.We previously identified an integrinα6-targeted peptide CRWYDENAC(RWY)that has been used for positron emission tomography(PET)imaging of HCC in mouse models.Methods:We labeled the integrinα6-targeted RWY peptide with cyanine 7(Cy7)to form an optical probe(Cy7-RWY)for near infrared fluorescent(NIRF)and photoacoustic(PA)imaging in HCC.Mice transplanted with subcutaneous HCC-LM3 or orthotopic HCC-H22 cells that overexpressed integrinα6 were intravenously injected with Cy7-RWY and its corresponding Cy7-control.NIRF and PA images of mice were collected from 0 to 48 h after injection.Results:Both NIRF and PA signals started to accumulate in the tumor 2 h after injection of Cy7-RWY and peaked at 24 h.Conclusions:Cy7-RWY is a promising optical probe for NIRF and PA imaging of HCC in mice,and has potential clinical application for HCC detection.
基金supported by the National Natural Science Foundation of China (Nos. 21622504, 21302050)the Hunan Provincial Natural Science Foundation of China (Nos. 14JJ2047)+1 种基金the Hunan University Fund for Multidisciplinary Developing (Nos. 2015JCA04)Open Funding Project of the State Key Laboratory of Bioreactor Engineering
文摘A new fluorescent probe（Rhod-Sec） for selenol detection with ultralow background fluorescence have been developed in this paper, which showed a 380-fold off-on fluorescence response, and the nontoxic Rhod-Sec is well suitable for detecting and imaging both exogenous and endogenous selenol in living cells. It also can be applied to visualize the fluctuation of selenol in HepG2 cells through LPS-induced cells oxidation resistance.
基金the National Natural Science Foundation of China(31371010,21673281)Youth Innovation Promotion Association of the Chinese Academy of Sciences(2012242)Key Research Project from the Ministry of Science and Technology of China(2017YFA0104300)
文摘A magnetic resonance(MR)-fluorescent dual-mode imaging probe was prepared by conjugating guaiazulene to Gd-DOTA,and used to label human mesenchymal stem cells(hMSCs)via electroporation.The probe self-assembled into nanoclusters in the cytoplasm,resulting in a significant reduction in T2-weighted signal intensity that persisted up to 7 days.The fluorescence signal of the probe was observed at 498 nm,and the labelled hMSCs emitted a green fluorescence.The MR-fluorescent dual-mode imaging probe can potentially be used for stem cell tracking in vivo.
基金the support from the National Natural Science Foundation of China(Nos.81971678 and 81671756)Key Research Project of Science and Technology Foundation of Hunan Province(Nos.2017SK2093,2018GK5004 and 2019SK2211)Projects of Medical and Health Technology Development Program in Shandong Province(No.2018WS471)。
文摘Au or other metal nanostructures have the ability to strongly quench the fluorescence of fluorophores.This feature has made AuNP-conjugates attractive for the construction of platforms for various bioanalytes to overcome the limitations of small molecule fluorophores(poor solubility,long reaction time).In this paper,an ultrafast"Turn-On"fluo rescent sensor for biothiols was constructed.The sensor is based on the fluorescent resonance energy transfer(FRET)effect between the fluorophore(PN)and AuNPs,which effectively quenches the fluorescence of the fluorophore.In the presence of thiols,PN is displaced and released from AuNP surfaces,and thus,the fluorescence is rapidly restored.The sensor features appreciable water solubility and ultrafast response time(a few seconds for Cys).In addition,it exhibits high selectivity and a detection limit as low as 12 nmol/L for Hcy.Moreover,the sensor presents good biocompatibility and has been successfully applied for imaging biothiols in living cells.
基金supported by the Introduction Research Item of Northwest University for Nationalities(No.xbmuyjrc201110)the Fundamental Research Funds for the Central Universities(Nos.zyz2012062 and 31920130024)the Young and Middle-Aged Scientists Research Fund of Northwest University for Nationalities(No.12XB34)
文摘A two-photon fluorescent probe TPZn was developed for specific ratiometric imaging Zn2＋ in living cells and tissues. Significant ratiometric fluorescence change was based on photoinduced electron transfer and intramolecular charge transfer. The synthetic method of TPZn was simple. It was successfully used to selectively image Zn2＋ based on the higher binding affinity for Zn2＋ than for Cd2＋. TPZn was easily loaded into the living cell and tissues with high membrane permeability in a complex biological environment. TPZn could clearly visualize endogenous Zn2＋ by TP ratiometric imaging in hippocampal slices at a depth of 120 μm. Thus, TPZn is a useful tool to image of Zn2＋ in living cells and tissues without interference from Cd2＋.
基金supported by National Natural Science Foundation of China(No.62175262)the Science and Technology Innovation Program of Hunan Province(No.2022RC1201)the Fundamental Research Funds for the Central Universities of Central South University(No.2019zzts849)。
文摘Combining phototherapy and chemotherapy has been considered a promising modality for cancer therapy due to their synergistic effect.Herein,we developed three D-π-A-structured boron dipyrromethenes(BODIPYs)(named as B-B,B-C,and B-C-Pt).Due to their enlargedπ-conjugated structure and high intramolecular charge transfer effect,the synthesized BODIPYs had photothermal conversion capability,and their absorption and fluorescence spectra were red-shifted.The cisplatin-appended BODIPY(B-C-Pt)exhibited good singlet oxygen(^1O_(2))generation ability and near infrared(NIR)absorption and fluorescence(λ_(Abs)=748 nm,λ_(Em)=947 nm).After being encapsulated by distearoyl phosphoethanolamine polyethyleneglycol 2000(DSPE-PEG-2000),which could inhibit the H-aggregation of B-C-Pt,the absorption and fluorescence of the obtained B-C-Pt nanoparticles(NPs)were red-shifted to 762 and 985 nm,respectively.The^1O_(2)quantum yield and photothermal conversion efficiency of the B-C-Pt NPs were 4.0%and 40.6%,respectively.Moreover,B-C-Pt NPs had chemotherapeutic efficacy due to the presence of cisplatin.In vitro and in vivo studies further demonstrated that B-C-Pt NPs had synergistic therapeutic efficacy.Together,B-C-Pt NPs could be employed in NIRⅡfluorescent and photoacoustic imaging-guided synergistic phototherapy and chemotherapy for cancer treatment.
基金the financial support from National Natural Science Foundation of China(No.51703135)the technical support from Beijing Key Laboratory of Optical Materials and Photonic Devices。
文摘Fluorescence-based imaging applications have been benefiting greatly from donor-acceptor(D-A)/donor-π-acceptor(D-π-A)fluorescent probes owing to their intramolecular charge transfer(ICT)nature and self-assembly behavior.In this study,we design and synthesize a hydrophilic D-A fluorescent probe,namely CHBA,which would self-assemble into interlaced textures down to nanoscale but disassemble by trace amount of water in fingertip area.Upon finger-pressing,it enables fingerprint imaging and covers level-1/2/3 fingerprint information,wherein the sweat pores can be mapped in both bright field model and fluorescence mode,capable of naked-eye-based similarity analysis for personal identity verification(PIV).Spectroscopic analysis and morphology study show that the working mechanism can be attributed to the selective water-erosion effect on the solid-liquid interphase under physical contact.The sweat pore information can be digitized by polar coordinate conversion,further allowing machine-learning-based analysis for PIV application.The final PIV accuracy reaches 100%for all the involved machine-learning models,with no erroneous judgements.A prototype of PIV system is constructed by integrating CHBA with artificial intelligence hardware,wherein the sweat pore imaging,data processing and the decisionmaking could be run in parallel,suggesting high feasibility in real-world application.
基金the National Natural Science Foundation of China(Nos.21877029,21735001)the National Key R&D Program of China(No.2019YFA0210103)+1 种基金the National Postdoctoral Program for Innovative Talents(No.BX20190110)the China Postdoctoral Science Foundation(No.2019M662758)。
文摘Fluorescent probes have been widely employed in biological imaging and sensing.However,it is always a challenge to design probes with high sensitivity.In this work,based on rhodamine skeleton,we developed a general strategy to construct sensitivity-enhanced fluorescent probe with the help of theoretical calculation for the first time.As a proof of concept,we synthesized a series of HOCl probes.Experiment results showed that with the C-9 of pyronin moiety of rhodamine stabilized by an electron donor group,probe DQF-S exhibited an importantly enhanced sensitivity(LOD:0.2 nmol/L)towards HOCl together with fast response time(<10 s).Moreover,due to the breaking symmetrical electron distribution by another electron donor group,the novel rhodamine probe DQF-S displayed a far red to near-infrared emission(>650 nm)and large Stokes shift.Bioimaging studies indicated that DQF-S can not only effectively detect basal HOCl in various types of cells,but also be successfully applied to image tumor tissue in vivo.These results demonstrate the potential of our design as a useful strategy to develop excellent fluorescent probes for bioimaging.
基金supported by the National Basic Research Program of China(2015CB352005)the National Natural Science Foundation of China(61525503/61378091/61620106016)+2 种基金Guangdong Natural Science Foundation Innovation Team(2014A030312008)Hong Kong,Macao and Taiwan cooperation innovation platform and major projects of international cooperation in Colleges and Universities in Guangdong Province(2015KGJHZ002)Shenzhen Basic Research Project(JCYJ20150930104948169/JCYJ20160328144746940/GJHZ 20160226202139185).
文摘Fluorescence litime imaging(FLIM)is an effective noninvasive bioanalytical tol based onmeasuring fuorescent lifetime of fuorophores.A growing number of FLIM studies utilizes ge-netically engineered fluorescent proteins targeted to specific subcellular structures to probe localmolecular environment,which opens new directions in cell science.This paper highlights theunconventional applications of FLIM for studies of molecular processes in diverse organelles oflive cultured cells.
