Using 2-dicyanomethylene-3-cyano-4,5,5-trimethyl-2,5-dihydrofuran(TCF)as a near-infrared fluorescent chromophore,we designed and synthesized a TCF-based fluorescent probe TCF-NS by introducing 2,4-dinitrophenyl ether ...Using 2-dicyanomethylene-3-cyano-4,5,5-trimethyl-2,5-dihydrofuran(TCF)as a near-infrared fluorescent chromophore,we designed and synthesized a TCF-based fluorescent probe TCF-NS by introducing 2,4-dinitrophenyl ether as the recognized site for H_(2)S.The probe TCF-NS displayed a rapid-response fluorescent against H_(2)S with high sensitivity and selection but had no significant fluorescence response to other biothiols.Furthermore,TCF-NS was applied to sense H_(2)S in living cells successfully with minimized cytotoxicity and a large Stokes shift.展开更多
Rheumatoid arthritis(RA)is a systemic autoimmune disease that is primarily manifested as synovitis and polyarticular opacity and typically leads to serious joint damage and irreversible disability,thus adversely affec...Rheumatoid arthritis(RA)is a systemic autoimmune disease that is primarily manifested as synovitis and polyarticular opacity and typically leads to serious joint damage and irreversible disability,thus adversely affecting locomotion ability and life quality.Consequently,good prognosis heavily relies on the early diagnosis and effective therapeutic monitoring of RA.Activatable fluorescent probes play vital roles in the detection and imaging of biomarkers for disease diagnosis and in vivo imaging.Herein,we review the fluorescent probes developed for the detection and imaging of RA biomarkers,namely reactive oxygen/nitrogen species(hypochlorous acid,peroxynitrite,hydroxyl radical,nitroxyl),pH,and cysteine,and address the related challenges and prospects to inspire the design of novel fluorescent probes and the improvement of their performance in RA studies.展开更多
In situ precise detection of bioactive molecules with high sensitivity and spatiotemporal resolution is essential for studying physiological events and disease diagnosis.The utilization of versatile fluorescent probes...In situ precise detection of bioactive molecules with high sensitivity and spatiotemporal resolution is essential for studying physiological events and disease diagnosis.The utilization of versatile fluorescent probes in fluorescence imaging offers a powerful tool for in vivo imaging of biomarkers closely associated with pathological conditions.However,the dynamic behavior leading to rapid clearance of small molecule probes from regions of interest severely compromises their potential for precise imaging.Notably,self-immobilizing fluorescent probes that selectively recognize diseased tissues while improving in situ retention and enrichment enable accurate high-fidelity fluorescence imaging.In this review,we aim to summarize the strategies employed for recent advances in the performance and precision of in vivo fluorescence imaging using self-immobilizing techniques.Lastly,we discuss the prospects and potential challenges associated with selfimmobilizing fluorescent probes to promote further development and application of more delicate fluorescent probes.展开更多
BACKGROUND The functional lumen imaging probe(FLIP)is a Food and Drug Administration approved tool to aid the diagnosis and management of esophageal disorders.However,widespread adoption of FLIP remains limited and it...BACKGROUND The functional lumen imaging probe(FLIP)is a Food and Drug Administration approved tool to aid the diagnosis and management of esophageal disorders.However,widespread adoption of FLIP remains limited and its utility in highvolume practices remains unclear.AIM To analyze large sample data on clinical use of FLIP and provide insight on several technical aspects when performing FLIP.METHODS We conducted a retrospective comparative and descriptive analysis of FLIP procedures performed by a single provider at an academic medical center.There was a total of 398 FLIP procedures identified.Patient medical records were reviewed and data regarding demographics and procedural details were collected.Statistical tests,including chi-squared,t-test,and multivariable logistic and linear regression,were performed.RESULTS There was an increase in FLIP cases with each successive time period of 13 months(n=68,146,184,respectively)with notable rises specifically for indications of dysphagia and gastroesophageal reflux disease.There was a shift toward use of the longer FLIP balloon catheter for diagnostic purposes(overall 70.4%vs 29.6%,P<0.01).Many cases(42.8%)were performed in conjunction with other diagnostics/interventions,such as dilation and wireless pH probe placement.Procedures were nearly equally performed with anesthesia vs moderate sedation(51.4%anesthesia),with no major complications.Patients who had anesthesia were less likely to have recurrent antegrade contractions[odds ratio(OR)=0.4,95%CI:0.3-0.8]and were also more likely to have absent contractility(OR=2.4,95%CI:1.3-CONCLUSION FLIP cases have increased in our practice with expanding indications for its use.Given limited normative data,providers should be aware of several potential technical issues,including the possible impact of sedation choice when assessing esophageal motility patterns.展开更多
Fluorescence imaging can provide valuable information on the expression,distribution,and activity of drug target proteins.Chemical probes are useful small-molecule tools for fluorescence imaging with high structural f...Fluorescence imaging can provide valuable information on the expression,distribution,and activity of drug target proteins.Chemical probes are useful small-molecule tools for fluorescence imaging with high structural flexibility and biocompatibility.In this review,we briefly introduce two classes of fluorescent probes for the visualization of drug target proteins.Enzymatically activatable probes make use of the specific enzymatic transformations that generally produce a fluorogenic response upon reacting with target enzymes.Alternatively,specific imaging can be conferred with a ligand that drives the probes to target proteins,where the labeling relies on noncovalent binding,covalent inhibition,or traceless labeling by ligand-directed chemistry.展开更多
Recent years have seen the design and implementation of many optical activatable smart probes.These probes are activatable because they change their optical properties and are smart because they can identify specific ...Recent years have seen the design and implementation of many optical activatable smart probes.These probes are activatable because they change their optical properties and are smart because they can identify specific targets.This broad class of detection agents has allowed previously unperformed visualizations,facilitating the study of diverse biomolecules including enzymes,nucleic acids,ions and reactive oxygen species.Designed to be robust in an in vivo environment,these probes have been used in tissue culture cells and in live small animals.An emerging class of smart probes has been designed to harness the potency of singlet oxygen generating photosensitizers.Combining the discrimination of activatable agents with the toxicity of photosensitizers represents a new and powerful approach to disease treatment.This review highlights some applications of activatable smart probes with a focus on developments of the past decade.展开更多
Tumor vaccination using tumor-associated antigenprimed dendritic cells(DCs)is in clinical trials.Investigators are using patients’own immune systems to activate T-cells against recurrent or metastatic tumors.Followin...Tumor vaccination using tumor-associated antigenprimed dendritic cells(DCs)is in clinical trials.Investigators are using patients’own immune systems to activate T-cells against recurrent or metastatic tumors.Following vaccination of DCs or attenuated tumor cells,clinical as well as radiological improvements have been noted due to migration and accumulation of cytotoxic T-cells(CTLs).CTLs mediated tumor cell killing resulted in extended survival in clinical trails and in preclinical models.Besides administration of primed DCs or attenuated or killed tumors cells to initiate the generation of CTLs,investigators have started making genetically altered T-cells(CTLs)to target specific tumors and showed in vivo migration and accumulation in the implanted or recurrent tumors using different imaging modalities.Our groups have also showed the utilization of both in vivo and in vitro techniques to make CTLs against glioma and used them as imaging probes to determine the sites of tumors.In this short review,the current status of vaccination therapy against glioma and utilization of CTLs as in vivo imaging probes to determine the sites of tumors and differentiate recurrent glioma from radiation necrosis will be discussed.展开更多
We report on tests of combined positron emission tomography(PET)andfluorescence molecular tomography(FMT)imaging system for in vivo investigation on small animals.A nude mouse was inoculated with MD-MB-231 breast canc...We report on tests of combined positron emission tomography(PET)andfluorescence molecular tomography(FMT)imaging system for in vivo investigation on small animals.A nude mouse was inoculated with MD-MB-231 breast cancer cells which expressed redfluorescent protein(RFP).For FMT system,reflective illumination mode was adopted with full-angle data acquisition.[18F]-Fluorodeoxyglucose([18F]-FDG)was used as radioactive tracer for PET.Both data were acquired simultaneously and then reconstructed separately before fusion.Fluorescent tomography results showed exactly where the tumor was located while PET results offered more metabolic information.Results confirmed feasibility for tumor detection and showed superiority to single modality imaging.展开更多
The diagnosis of bacterial infections remains a major challenge in medicine.Optical imaging of bacterial infection in living animals is usually conducted with genetic reporters such as lightemitting encymes or fluores...The diagnosis of bacterial infections remains a major challenge in medicine.Optical imaging of bacterial infection in living animals is usually conducted with genetic reporters such as lightemitting encymes or fluorescent proteins.However,there are many circumstances where genetic reporters are not applicable,and there is an urgent need for exogenous synthetic probes that can selectively target bacteria.Optical imaging of bacteria in vivo is much less developed than methods such as ndioimaging and MRI.Furthermore near infrared(NIR)dyes with emision wavelengths in the region of 650-900 rm can propagate through two or more centimeters of tissue and may enable deeper tisue imaging if sensitive detection techniques are employed.Here we constructed an antimicrobial peptide fragment UBI29-41-based near infrared fuorescent imaging probe.The probe is composed of UBI2941 conjugated to a near infraured dye ICG Der-02.UBI29-41 is a cationic antimicrobial peptide that targets the anionic surfaces of bacterial cells.The probe allows detection of Staphylococcus aureus infection(5×10^(7)cells)in a mouse local infection model using whole animal nearinfrared fuorescence imaging.Furthermore,we demonstrate that the UBI29-41-based imaging probe can selectively accumulate within bacteria.The significantly higher accumulation in bacterial infection suggests that UBI29-41-based imaging probe may be a promising imaging agent to detect bacterial infections.展开更多
The study designed a polyacrylic acid(PAA)modified Fe3O4@MnO2 nanoparticles(Fe3O4@MnO2@PAA)for T1/T2 dualmode imaging.In addition,this nano-drug has pH response and anti-tumor photothermal therapy.First,using Fe3O4 as...The study designed a polyacrylic acid(PAA)modified Fe3O4@MnO2 nanoparticles(Fe3O4@MnO2@PAA)for T1/T2 dualmode imaging.In addition,this nano-drug has pH response and anti-tumor photothermal therapy.First,using Fe3O4 as the core can significantly reduce the signal of Fe3O4@MnO2@PAA nanoparticles.MnO2 nanoshells can be decomposed into paramagnetic Mn2+under the acidic environment in the tumor,which enhanced the T1 signal.The pH-responsive T1/T2 dual-mode magnetic resonance imaging(MRI)contrast agent had good sensitivity and specificity,providing more comprehensive and detailed information for tumor diagnosis.In addition,Fe3O4@MnO2@PAA nanoparticles showed excellent absorption capacity in the near-infrared region(NIR),which could be used as a good photothermal conversion material to mediate photothermal treatment of tumors.Therefore,the pHresponsive dual-mode MRI nanoparticle-mediated photothermal therapy showed good application potential in tumor treatment and diagnosis.展开更多
A facile strategy to fabricate gold nanorod@polyacrylic acid/calcium phosphate(Au NR@-PAA/Ca P) yolk–shell nanoparticles(NPs) composed with a PAA/Ca P shell and an Au NR yolk is reported. The asobtained Au NR@PAA/Ca ...A facile strategy to fabricate gold nanorod@polyacrylic acid/calcium phosphate(Au NR@-PAA/Ca P) yolk–shell nanoparticles(NPs) composed with a PAA/Ca P shell and an Au NR yolk is reported. The asobtained Au NR@PAA/Ca P yolk–shell NPs possess ultrahigh doxorubicin(DOX) loading capability(1 mg DOX/mg NPs), superior photothermal conversion property(26%)and p H/near-infrared(NIR) dual-responsive drug delivery performance. The released DOX continuously increased due to the damage of the Ca P shell at low p H values. When the DOX-loaded Au NR@PAA/Ca P yolk–shell NPs wereexposed to NIR irradiation, a burst-like drug release occurs owing to the heat produced by the Au NRs. Furthermore,Au NR@PAA/Ca P yolk–shell NPs are successfully employed for synergic dual-mode X-ray computed tomography/photoacoustic imaging and chemo-photothermal cancer therapy. Therefore, this work brings new insights for the synthesis of multifunctional nanomaterials and extends theranostic applications.展开更多
AIM: To experimentally investigate the acoustical behavior of different dual-mode nanosized contrast agents(NPCAs) for echographic medical imaging at low ultrasound(US) frequency. METHODS: We synthesized three differe...AIM: To experimentally investigate the acoustical behavior of different dual-mode nanosized contrast agents(NPCAs) for echographic medical imaging at low ultrasound(US) frequency. METHODS: We synthesized three different nanosized structures:(1) Pure silica nanospheres(SiNSs);(2) FePt-iron oxide(FePt-IO)-coated SiNSs; and(3) IOcoated SiNSs, employing three different diameter of SiNS-core(160, 330 and 660 nm). Tissue mimicking phantoms made of agarose gel solution containing 5 mg of different NPCAs in 2 mL-Eppendorf tubes, were insonified by a commercial echographic system at three different low US pulse values(2.5, 3.5 and 4.5 MHz). The raw radiofrequency signal, backscattered from each considered NPCA containing sample, has been processed in order to calculate the US average backscatter intensity and compare the acoustic behavior of the different NPCA types. RESULTS: The highest US contrast was exhibited by pure SiNSs; FePt-IO-coated SiNSs acoustical behavior followed a similar trend of pure SiNSs with a slight difference in terms of brightness values. The acoustic response of the examined NPCAs resulted function of both SiNS diameter and US frequency. Specifically, higher US frequencies determined higher value of the backscatter for a given SiNS diameter. Frequencydependent enhancement was marked for pure SiNSs and became less remarkable for FePt-IO-coated SiNSs, whereas IO-coated SiNSs resulted almost unaffected by such frequency variations. Pure and FePt-IO-coated SiNSs evidenced an image backscatter increasing with the diameter up to 330 nm. Conversely, among the types of NPCA tested, IO-coated SiNSs showed the lowest acoustical response for each synthesized diameter and employed US frequency, although a diameter-dependent raising trend was evidenced. CONCLUSION: The US characterization of magnetically covered SiNS shows that FePt-IO, rather than IO, was the best magnetic coating for realizing NPCAs suitable for dual mode imaging of deep organs, combining US and magnetic resonance imaging.展开更多
A fluorescence ratiometric probe 1 for cysteine (Cys) and homocysteine (Hcy) has been rationally constructed based on intramolecular charge transfer (ICT) mechanism. Upon treatment with Cys/Hcy, probe 1 exhibited a fl...A fluorescence ratiometric probe 1 for cysteine (Cys) and homocysteine (Hcy) has been rationally constructed based on intramolecular charge transfer (ICT) mechanism. Upon treatment with Cys/Hcy, probe 1 exhibited a fluorescence ratiometric response, with the emission wavelength displaying a large shift (from 526 nm to 446 nm). When 90 μM Cys were added, the emission ratios (I446/I526) of the probe changed dramatically from 0.01797 to 4.65472. The detection limit was also measured to be 0.18 μM (S/N = 3). The theoretical calculations have confirmed that the ratiometric response of probe 1 to Cys/Hcy is due to the inhibition of ICT process upon the reaction of probe 1 with Cys/Hcy. Furthermore, the fluorescence imaging experiments in living cell demonstrated that probe 1 was favourable for intracellular Cys/Hcy imaging.展开更多
The detection of biothiols such as cysteine(Cys),homocysteine(Hcy),and glutathione(GSH)are critical for understanding their roles in biology and their involvement in various physiological and pathological processes.Re...The detection of biothiols such as cysteine(Cys),homocysteine(Hcy),and glutathione(GSH)are critical for understanding their roles in biology and their involvement in various physiological and pathological processes.Recently,significant progress has been made in constructing fluorescent probes capable of detecting and visualizing biothiols.This review provides an in-depth look at the latest advancements in simultaneous and selective molecular probes,focusing on developments over the last 5 years.We examine design techniques,sensing mechanisms,and imaging methods to assess their effectiveness and responsiveness to thiols.Additionally,we discuss the prevailing challenges and offer recommendations to address them.展开更多
Investigating gastrointestinal(GI)motility disorders relies on diagnostic tools to assess muscular contractions,peristalsis propagation and the integrity and coordination of various sphincters.Manometries are the gold...Investigating gastrointestinal(GI)motility disorders relies on diagnostic tools to assess muscular contractions,peristalsis propagation and the integrity and coordination of various sphincters.Manometries are the gold standard to study the GI motor function but it is increasingly acknowledged that manometries do not provide a complete picture in relation to sphincters competencies and muscle fibrosis.Endolumenal functional lumen imaging probe(EndoFLIP)an emerging technology,uses impedance planimetry to measure hollow organs cross sectional area,distensibility and compliance.It has been successfully used as a complementary tool in the assessment of the upper and lower oesophageal sphincters,oesophageal body,the pylorus and the anal canal.In this article,we aim to review the uses of EndoFLIP as a tool to investigate GI motility disorders with a special focus on paediatric practice.The majority of EndoFLIP studies were conducted in adult patients but the uptake of the technology in paediatrics is increasing.EndoFLIP can provide a useful complementary data to the existing GI motility investigation in both children and adults.展开更多
It is extremely important for bacteria detection in many fields,such as medical diagnosis and food safety.In this paper,streptavidin functionalized quantum dots(SA-QDs),as a nano-fluorescent probe,were used to attach ...It is extremely important for bacteria detection in many fields,such as medical diagnosis and food safety.In this paper,streptavidin functionalized quantum dots(SA-QDs),as a nano-fluorescent probe,were used to attach with Escherichia coli(E.coli) for the detection and identification of bacteria with immunoreactions and biotin-streptavidin affinity.Fluorescent images of the bacteria and the fluorescence intensity were used to evaluate the conjugation effect with different incubation time.Our results showed that 20 min is a reasonable incubation time for the SA-QDs coupling to E.coli cells.The fluorescent images,which produce a greatly amplified and enhanced signal of E.coli cells,were obtained through the immunological amplification and fluorescent probe enrichment steps.In addition,the bleaching process of SA-QDs without any encapsulation at room temperature was clearly observed during 10 min of being excited.Our work provided a modularized sample treatment method using SA-QDs as a nano-fluorescent probe in cellular imaging and bio-labeling.展开更多
Fluorescent probe is an important tool for investigation of biological events in plant tissues.However,the research on small-molecule based fluorescent probe for plant imaging still stays at the initial stage.In order...Fluorescent probe is an important tool for investigation of biological events in plant tissues.However,the research on small-molecule based fluorescent probe for plant imaging still stays at the initial stage.In order to noninvasively achieve the subcellular information of Arabidopsis thaliana,a two-photon and fluorene based fluorophore with a bi-oligo(ethylene glycol)functional group was synthesized.Under the laser's irradiation at 750 nm,the subcellular structures of Arabidopsis thaliana including stomata and root tips were clearly observed without slicing,which displayed significant superiorities over traditional single-photon excitation microscopy.Subsequently,the above functionalized fluorophore was further modified with a recognition group(dipicolylamine)to form a smart fluorescent probe(LJTP1).As results,LJTP1 not only can sensitively detect Cu^(2+)/S^(2-)with fluorescence“on-off-on”response in vitro and in vivo,but also can achieve noninvasive imaging in Arabidopsis thaliana tissues under two-photon microscopy.We believe this study will open up a new mind for noninvasive imaging in plant tissues.展开更多
Mesoporous structured MnSiO3@Fe3O4@C nanoparticles(NPs)were prepared via a facile and efficient strategy,with negligible cytotoxicity and minor side efforts.The as-prepared MnSiO3@Fe3O4@C NPs hold great potential in s...Mesoporous structured MnSiO3@Fe3O4@C nanoparticles(NPs)were prepared via a facile and efficient strategy,with negligible cytotoxicity and minor side efforts.The as-prepared MnSiO3@Fe3O4@C NPs hold great potential in serving as pH-responsive T1-T2^*dual-modal magnetic resonance(MR)imaging contrast agents.The released Mn^2+shortened T1 relaxation time,meanwhile the superparamagnetic Fe3O4 enhanced T2 contrast imaging.The release rate of Mn ions reaches 31.66%under the condition of pH=5.0,which is similar to tumor microenvironment and organelles.Cytotoxicity assays show that MnSiO3@Fe3O4@C NPs have minor toxicity,even at high concentrations.After intravenous injection of MnSiO3@Fe3O4@C NPs,a rapid contrast enhancement in tumors was achieved with a significant enhancement of 132%after 24 h of the administration.Moreover,a significant decreasement of 53.8%was witnessed in T2 MR imaging signal.It demonstrated that MnSiO3@Fe3O4@C NPs can act as both positive and negative MR imaging contrast agents.Besides,owing to the pH-responsive degradation of mesoporous MnSiO3,MnSiO3@Fe3O4@C NPs can also be used as potential drug systems for cancer theranostics.展开更多
Hepatocellular carcinoma(HCC)is a highly aggressive liver malignancy and the main form of liver cancer.Early diagnosis and treatment of HCC can effectively reduce mortality.Carboxylesterase(CE)-specific detection and ...Hepatocellular carcinoma(HCC)is a highly aggressive liver malignancy and the main form of liver cancer.Early diagnosis and treatment of HCC can effectively reduce mortality.Carboxylesterase(CE)-specific detection and imaging can be used for early diagnosis and image-guided surgical of HCC.However,traditional optical probes suffer from poor selectivity and low imaging signal-to-noise ratio.Here,we have constructed a series of chemiluminescent probes for carboxylesterase detection based on the strategy of enzymatic pocket-oriented steric tailoring techniques.The probes with different unique and excellent properties have been obtained through the structure-based steric hindrance adjustment on the recognition site.Here,CE-2 has been successfully used for high-throughput screening of rapid carboxylesterase inhibitors due to its extremely low detection limit(2.5×10^(-4)U mL^(-1))and fast recognition ability.CE-3 has been successfully used for image-guided surgery of orthotopic hepatocellular carcinoma due to its ultra-long chemiluminescence imaging(over 12 h)of hepatocellular carcinoma.This study may promote advances in the rapid detection and screening of inhibitory drugs for CE and the field of surgical navigation in HCC.展开更多
基金financially supported by the Natural Science Foundation of Jiangsu Province(Grant No.BK20241181)the State Key Laboratory of AnalyticalChemistry for Life Science,School of Chemistry and Chemical Engineering,Nanjing University(Grant No.SKLACLS2419)。
文摘Using 2-dicyanomethylene-3-cyano-4,5,5-trimethyl-2,5-dihydrofuran(TCF)as a near-infrared fluorescent chromophore,we designed and synthesized a TCF-based fluorescent probe TCF-NS by introducing 2,4-dinitrophenyl ether as the recognized site for H_(2)S.The probe TCF-NS displayed a rapid-response fluorescent against H_(2)S with high sensitivity and selection but had no significant fluorescence response to other biothiols.Furthermore,TCF-NS was applied to sense H_(2)S in living cells successfully with minimized cytotoxicity and a large Stokes shift.
基金supported by the National Natural Science Foundation of China(82072432)the China-Japan Friendship Hospital Horizontal Project/Spontaneous Research Funding(2022-HX-JC-7)+1 种基金the National High Level Hospital Clinical Research Funding(2022-NHLHCRF-PY-20)the Elite Medical Professionals project of China-Japan Friendship Hospital(ZRJY2021-GG12).
文摘Rheumatoid arthritis(RA)is a systemic autoimmune disease that is primarily manifested as synovitis and polyarticular opacity and typically leads to serious joint damage and irreversible disability,thus adversely affecting locomotion ability and life quality.Consequently,good prognosis heavily relies on the early diagnosis and effective therapeutic monitoring of RA.Activatable fluorescent probes play vital roles in the detection and imaging of biomarkers for disease diagnosis and in vivo imaging.Herein,we review the fluorescent probes developed for the detection and imaging of RA biomarkers,namely reactive oxygen/nitrogen species(hypochlorous acid,peroxynitrite,hydroxyl radical,nitroxyl),pH,and cysteine,and address the related challenges and prospects to inspire the design of novel fluorescent probes and the improvement of their performance in RA studies.
基金The financial supports provided, in whole or in part, by the National Natural Science Foundation of China （81071257, 81201192, 81 lO1147, 11272083 ）, Postdoctal Program of China （2011M501297, 2012T50715 ） , and the Fundamental Research Funds for Central Uni- versities （ ZYGX2010X019, ZYGX201OJ101, ZYGX2011 J099） , are greatly appreciated.
基金support from the National Natural Science Foundation of China(No.22274005,U2167222)the Science Fund for Creative Research Groups of Nature Science Foundation of Hebei Province(B2021201038)+4 种基金Natural Science Foundation of Hebei Province(B2023201108)Hebei Province Higher Education Science and Technology Research Project(JZX2023001)Research and Innovation Team of Hebei University(IT2023A01)Hebei Province Innovation Capability Enhancement Plan Project(22567632H)Open Research Fund of School of Chemistry and Chemical Engineering,Henan Normal University.
文摘In situ precise detection of bioactive molecules with high sensitivity and spatiotemporal resolution is essential for studying physiological events and disease diagnosis.The utilization of versatile fluorescent probes in fluorescence imaging offers a powerful tool for in vivo imaging of biomarkers closely associated with pathological conditions.However,the dynamic behavior leading to rapid clearance of small molecule probes from regions of interest severely compromises their potential for precise imaging.Notably,self-immobilizing fluorescent probes that selectively recognize diseased tissues while improving in situ retention and enrichment enable accurate high-fidelity fluorescence imaging.In this review,we aim to summarize the strategies employed for recent advances in the performance and precision of in vivo fluorescence imaging using self-immobilizing techniques.Lastly,we discuss the prospects and potential challenges associated with selfimmobilizing fluorescent probes to promote further development and application of more delicate fluorescent probes.
基金The study was approved by the Stanford University IRB:53329.
文摘BACKGROUND The functional lumen imaging probe(FLIP)is a Food and Drug Administration approved tool to aid the diagnosis and management of esophageal disorders.However,widespread adoption of FLIP remains limited and its utility in highvolume practices remains unclear.AIM To analyze large sample data on clinical use of FLIP and provide insight on several technical aspects when performing FLIP.METHODS We conducted a retrospective comparative and descriptive analysis of FLIP procedures performed by a single provider at an academic medical center.There was a total of 398 FLIP procedures identified.Patient medical records were reviewed and data regarding demographics and procedural details were collected.Statistical tests,including chi-squared,t-test,and multivariable logistic and linear regression,were performed.RESULTS There was an increase in FLIP cases with each successive time period of 13 months(n=68,146,184,respectively)with notable rises specifically for indications of dysphagia and gastroesophageal reflux disease.There was a shift toward use of the longer FLIP balloon catheter for diagnostic purposes(overall 70.4%vs 29.6%,P<0.01).Many cases(42.8%)were performed in conjunction with other diagnostics/interventions,such as dilation and wireless pH probe placement.Procedures were nearly equally performed with anesthesia vs moderate sedation(51.4%anesthesia),with no major complications.Patients who had anesthesia were less likely to have recurrent antegrade contractions[odds ratio(OR)=0.4,95%CI:0.3-0.8]and were also more likely to have absent contractility(OR=2.4,95%CI:1.3-CONCLUSION FLIP cases have increased in our practice with expanding indications for its use.Given limited normative data,providers should be aware of several potential technical issues,including the possible impact of sedation choice when assessing esophageal motility patterns.
基金This work was funded by Japan Science and Technology Agency(JST)ERATO Grant JPMJER1802 and a Grant-in-Aid for Scientific Research on Innovative Areas“Chemistry for Multimolecular Crowding Biosystems”(17H06348).
文摘Fluorescence imaging can provide valuable information on the expression,distribution,and activity of drug target proteins.Chemical probes are useful small-molecule tools for fluorescence imaging with high structural flexibility and biocompatibility.In this review,we briefly introduce two classes of fluorescent probes for the visualization of drug target proteins.Enzymatically activatable probes make use of the specific enzymatic transformations that generally produce a fluorogenic response upon reacting with target enzymes.Alternatively,specific imaging can be conferred with a ligand that drives the probes to target proteins,where the labeling relies on noncovalent binding,covalent inhibition,or traceless labeling by ligand-directed chemistry.
基金supported by Canadian Cancer Society Grant#018510 through the National Cancer Institute of Canada.
文摘Recent years have seen the design and implementation of many optical activatable smart probes.These probes are activatable because they change their optical properties and are smart because they can identify specific targets.This broad class of detection agents has allowed previously unperformed visualizations,facilitating the study of diverse biomolecules including enzymes,nucleic acids,ions and reactive oxygen species.Designed to be robust in an in vivo environment,these probes have been used in tissue culture cells and in live small animals.An emerging class of smart probes has been designed to harness the potency of singlet oxygen generating photosensitizers.Combining the discrimination of activatable agents with the toxicity of photosensitizers represents a new and powerful approach to disease treatment.This review highlights some applications of activatable smart probes with a focus on developments of the past decade.
文摘Tumor vaccination using tumor-associated antigenprimed dendritic cells(DCs)is in clinical trials.Investigators are using patients’own immune systems to activate T-cells against recurrent or metastatic tumors.Following vaccination of DCs or attenuated tumor cells,clinical as well as radiological improvements have been noted due to migration and accumulation of cytotoxic T-cells(CTLs).CTLs mediated tumor cell killing resulted in extended survival in clinical trails and in preclinical models.Besides administration of primed DCs or attenuated or killed tumors cells to initiate the generation of CTLs,investigators have started making genetically altered T-cells(CTLs)to target specific tumors and showed in vivo migration and accumulation in the implanted or recurrent tumors using different imaging modalities.Our groups have also showed the utilization of both in vivo and in vitro techniques to make CTLs against glioma and used them as imaging probes to determine the sites of tumors.In this short review,the current status of vaccination therapy against glioma and utilization of CTLs as in vivo imaging probes to determine the sites of tumors and differentiate recurrent glioma from radiation necrosis will be discussed.
基金The authors would like to thank X.Zhang,faculty of XinAoMDT Technology Co.,Ltd.,for the work of system software development.This work is supported by the National Natural Science Foundation of China under Grant Nos.81071191,60831003,30930092,30872633the Tsinghua-Yue-Yuen Medical Science Foundationthe National Basic Research Program of China(973)under Grant No.2011CB707701.
文摘We report on tests of combined positron emission tomography(PET)andfluorescence molecular tomography(FMT)imaging system for in vivo investigation on small animals.A nude mouse was inoculated with MD-MB-231 breast cancer cells which expressed redfluorescent protein(RFP).For FMT system,reflective illumination mode was adopted with full-angle data acquisition.[18F]-Fluorodeoxyglucose([18F]-FDG)was used as radioactive tracer for PET.Both data were acquired simultaneously and then reconstructed separately before fusion.Fluorescent tomography results showed exactly where the tumor was located while PET results offered more metabolic information.Results confirmed feasibility for tumor detection and showed superiority to single modality imaging.
基金The authors are grateful to Natural Science Foun-dation Committee of China(NSFC 81220108012,81171395,81071194,81000666,30970776,30672015,30800257 and 31050110123)the Ministry of Science and Technology(2009ZX09310-004)the Pri-ority Academic Program Development of Jiangsu Higher Education Institutions for their financial support.
文摘The diagnosis of bacterial infections remains a major challenge in medicine.Optical imaging of bacterial infection in living animals is usually conducted with genetic reporters such as lightemitting encymes or fluorescent proteins.However,there are many circumstances where genetic reporters are not applicable,and there is an urgent need for exogenous synthetic probes that can selectively target bacteria.Optical imaging of bacteria in vivo is much less developed than methods such as ndioimaging and MRI.Furthermore near infrared(NIR)dyes with emision wavelengths in the region of 650-900 rm can propagate through two or more centimeters of tissue and may enable deeper tisue imaging if sensitive detection techniques are employed.Here we constructed an antimicrobial peptide fragment UBI29-41-based near infrared fuorescent imaging probe.The probe is composed of UBI2941 conjugated to a near infraured dye ICG Der-02.UBI29-41 is a cationic antimicrobial peptide that targets the anionic surfaces of bacterial cells.The probe allows detection of Staphylococcus aureus infection(5×10^(7)cells)in a mouse local infection model using whole animal nearinfrared fuorescence imaging.Furthermore,we demonstrate that the UBI29-41-based imaging probe can selectively accumulate within bacteria.The significantly higher accumulation in bacterial infection suggests that UBI29-41-based imaging probe may be a promising imaging agent to detect bacterial infections.
文摘The study designed a polyacrylic acid(PAA)modified Fe3O4@MnO2 nanoparticles(Fe3O4@MnO2@PAA)for T1/T2 dualmode imaging.In addition,this nano-drug has pH response and anti-tumor photothermal therapy.First,using Fe3O4 as the core can significantly reduce the signal of Fe3O4@MnO2@PAA nanoparticles.MnO2 nanoshells can be decomposed into paramagnetic Mn2+under the acidic environment in the tumor,which enhanced the T1 signal.The pH-responsive T1/T2 dual-mode magnetic resonance imaging(MRI)contrast agent had good sensitivity and specificity,providing more comprehensive and detailed information for tumor diagnosis.In addition,Fe3O4@MnO2@PAA nanoparticles showed excellent absorption capacity in the near-infrared region(NIR),which could be used as a good photothermal conversion material to mediate photothermal treatment of tumors.Therefore,the pHresponsive dual-mode MRI nanoparticle-mediated photothermal therapy showed good application potential in tumor treatment and diagnosis.
基金the National Natural Science Foundation of China(Grant Nos.21573040 and 21603029)the Natural Science Foundation and Science and Technology Development Planning of Jilin Province(20150204086GX and20170520148JH)+3 种基金the Fundamental Research Funds for the Central Universities(2412016KJ007 and 2412016KJ020)the China Postdoctoral Science Foundation(2016M600224)the Jilin Provincial Research Foundation for Basic Research(20160519012JH)Jilin Provincial Key Laboratory of Advanced Energy Materials(Northeast Normal University)
文摘A facile strategy to fabricate gold nanorod@polyacrylic acid/calcium phosphate(Au NR@-PAA/Ca P) yolk–shell nanoparticles(NPs) composed with a PAA/Ca P shell and an Au NR yolk is reported. The asobtained Au NR@PAA/Ca P yolk–shell NPs possess ultrahigh doxorubicin(DOX) loading capability(1 mg DOX/mg NPs), superior photothermal conversion property(26%)and p H/near-infrared(NIR) dual-responsive drug delivery performance. The released DOX continuously increased due to the damage of the Ca P shell at low p H values. When the DOX-loaded Au NR@PAA/Ca P yolk–shell NPs wereexposed to NIR irradiation, a burst-like drug release occurs owing to the heat produced by the Au NRs. Furthermore,Au NR@PAA/Ca P yolk–shell NPs are successfully employed for synergic dual-mode X-ray computed tomography/photoacoustic imaging and chemo-photothermal cancer therapy. Therefore, this work brings new insights for the synthesis of multifunctional nanomaterials and extends theranostic applications.
基金Supported by Italian Ministry of Instruction and Research,No.DM18604-Bando Laboratori-DD MIUR 14.5.2005 n.602/Ric/2005FESR PO Apulia Region 2007-2013-Action 1.2.4,No.3Q5AX31the Progetto Bandiera NANOMAX ENCODER
文摘AIM: To experimentally investigate the acoustical behavior of different dual-mode nanosized contrast agents(NPCAs) for echographic medical imaging at low ultrasound(US) frequency. METHODS: We synthesized three different nanosized structures:(1) Pure silica nanospheres(SiNSs);(2) FePt-iron oxide(FePt-IO)-coated SiNSs; and(3) IOcoated SiNSs, employing three different diameter of SiNS-core(160, 330 and 660 nm). Tissue mimicking phantoms made of agarose gel solution containing 5 mg of different NPCAs in 2 mL-Eppendorf tubes, were insonified by a commercial echographic system at three different low US pulse values(2.5, 3.5 and 4.5 MHz). The raw radiofrequency signal, backscattered from each considered NPCA containing sample, has been processed in order to calculate the US average backscatter intensity and compare the acoustic behavior of the different NPCA types. RESULTS: The highest US contrast was exhibited by pure SiNSs; FePt-IO-coated SiNSs acoustical behavior followed a similar trend of pure SiNSs with a slight difference in terms of brightness values. The acoustic response of the examined NPCAs resulted function of both SiNS diameter and US frequency. Specifically, higher US frequencies determined higher value of the backscatter for a given SiNS diameter. Frequencydependent enhancement was marked for pure SiNSs and became less remarkable for FePt-IO-coated SiNSs, whereas IO-coated SiNSs resulted almost unaffected by such frequency variations. Pure and FePt-IO-coated SiNSs evidenced an image backscatter increasing with the diameter up to 330 nm. Conversely, among the types of NPCA tested, IO-coated SiNSs showed the lowest acoustical response for each synthesized diameter and employed US frequency, although a diameter-dependent raising trend was evidenced. CONCLUSION: The US characterization of magnetically covered SiNS shows that FePt-IO, rather than IO, was the best magnetic coating for realizing NPCAs suitable for dual mode imaging of deep organs, combining US and magnetic resonance imaging.
文摘A fluorescence ratiometric probe 1 for cysteine (Cys) and homocysteine (Hcy) has been rationally constructed based on intramolecular charge transfer (ICT) mechanism. Upon treatment with Cys/Hcy, probe 1 exhibited a fluorescence ratiometric response, with the emission wavelength displaying a large shift (from 526 nm to 446 nm). When 90 μM Cys were added, the emission ratios (I446/I526) of the probe changed dramatically from 0.01797 to 4.65472. The detection limit was also measured to be 0.18 μM (S/N = 3). The theoretical calculations have confirmed that the ratiometric response of probe 1 to Cys/Hcy is due to the inhibition of ICT process upon the reaction of probe 1 with Cys/Hcy. Furthermore, the fluorescence imaging experiments in living cell demonstrated that probe 1 was favourable for intracellular Cys/Hcy imaging.
基金XLS thanks the National Natural Science Foundation of China(No.21907080,22278330)the Youth Innovative Team(No.xtr052022012)from Xi'an Jiaotong Universitysupported by the Natural Science Basic Research Program of Shaanxi(Program No.2023-JC-QN-0246).
文摘The detection of biothiols such as cysteine(Cys),homocysteine(Hcy),and glutathione(GSH)are critical for understanding their roles in biology and their involvement in various physiological and pathological processes.Recently,significant progress has been made in constructing fluorescent probes capable of detecting and visualizing biothiols.This review provides an in-depth look at the latest advancements in simultaneous and selective molecular probes,focusing on developments over the last 5 years.We examine design techniques,sensing mechanisms,and imaging methods to assess their effectiveness and responsiveness to thiols.Additionally,we discuss the prevailing challenges and offer recommendations to address them.
文摘Investigating gastrointestinal(GI)motility disorders relies on diagnostic tools to assess muscular contractions,peristalsis propagation and the integrity and coordination of various sphincters.Manometries are the gold standard to study the GI motor function but it is increasingly acknowledged that manometries do not provide a complete picture in relation to sphincters competencies and muscle fibrosis.Endolumenal functional lumen imaging probe(EndoFLIP)an emerging technology,uses impedance planimetry to measure hollow organs cross sectional area,distensibility and compliance.It has been successfully used as a complementary tool in the assessment of the upper and lower oesophageal sphincters,oesophageal body,the pylorus and the anal canal.In this article,we aim to review the uses of EndoFLIP as a tool to investigate GI motility disorders with a special focus on paediatric practice.The majority of EndoFLIP studies were conducted in adult patients but the uptake of the technology in paediatrics is increasing.EndoFLIP can provide a useful complementary data to the existing GI motility investigation in both children and adults.
基金Sponsored by the Knowledge Innovation Program of the Chinese Academy of Sciences (KGCX2-YW-111-2)the National Hi-Tech Research and Development Program of China (Grant No. 2007AA03Z428)National Natural Science Foundation of China (Grant No. 60801032)
文摘It is extremely important for bacteria detection in many fields,such as medical diagnosis and food safety.In this paper,streptavidin functionalized quantum dots(SA-QDs),as a nano-fluorescent probe,were used to attach with Escherichia coli(E.coli) for the detection and identification of bacteria with immunoreactions and biotin-streptavidin affinity.Fluorescent images of the bacteria and the fluorescence intensity were used to evaluate the conjugation effect with different incubation time.Our results showed that 20 min is a reasonable incubation time for the SA-QDs coupling to E.coli cells.The fluorescent images,which produce a greatly amplified and enhanced signal of E.coli cells,were obtained through the immunological amplification and fluorescent probe enrichment steps.In addition,the bleaching process of SA-QDs without any encapsulation at room temperature was clearly observed during 10 min of being excited.Our work provided a modularized sample treatment method using SA-QDs as a nano-fluorescent probe in cellular imaging and bio-labeling.
基金supported by the National Natural Science Foundation of China(21806048,21801086 and 22071072).
文摘Fluorescent probe is an important tool for investigation of biological events in plant tissues.However,the research on small-molecule based fluorescent probe for plant imaging still stays at the initial stage.In order to noninvasively achieve the subcellular information of Arabidopsis thaliana,a two-photon and fluorene based fluorophore with a bi-oligo(ethylene glycol)functional group was synthesized.Under the laser's irradiation at 750 nm,the subcellular structures of Arabidopsis thaliana including stomata and root tips were clearly observed without slicing,which displayed significant superiorities over traditional single-photon excitation microscopy.Subsequently,the above functionalized fluorophore was further modified with a recognition group(dipicolylamine)to form a smart fluorescent probe(LJTP1).As results,LJTP1 not only can sensitively detect Cu^(2+)/S^(2-)with fluorescence“on-off-on”response in vitro and in vivo,but also can achieve noninvasive imaging in Arabidopsis thaliana tissues under two-photon microscopy.We believe this study will open up a new mind for noninvasive imaging in plant tissues.
基金supported by the National Natural Science Foundation of China(No.21571168)
文摘Mesoporous structured MnSiO3@Fe3O4@C nanoparticles(NPs)were prepared via a facile and efficient strategy,with negligible cytotoxicity and minor side efforts.The as-prepared MnSiO3@Fe3O4@C NPs hold great potential in serving as pH-responsive T1-T2^*dual-modal magnetic resonance(MR)imaging contrast agents.The released Mn^2+shortened T1 relaxation time,meanwhile the superparamagnetic Fe3O4 enhanced T2 contrast imaging.The release rate of Mn ions reaches 31.66%under the condition of pH=5.0,which is similar to tumor microenvironment and organelles.Cytotoxicity assays show that MnSiO3@Fe3O4@C NPs have minor toxicity,even at high concentrations.After intravenous injection of MnSiO3@Fe3O4@C NPs,a rapid contrast enhancement in tumors was achieved with a significant enhancement of 132%after 24 h of the administration.Moreover,a significant decreasement of 53.8%was witnessed in T2 MR imaging signal.It demonstrated that MnSiO3@Fe3O4@C NPs can act as both positive and negative MR imaging contrast agents.Besides,owing to the pH-responsive degradation of mesoporous MnSiO3,MnSiO3@Fe3O4@C NPs can also be used as potential drug systems for cancer theranostics.
基金supported by the National Natural Science Foundation of China (82272067,22107123,and M-0696)the Natural Science Foundation of Hunan Province (2022JJ80052)。
文摘Hepatocellular carcinoma(HCC)is a highly aggressive liver malignancy and the main form of liver cancer.Early diagnosis and treatment of HCC can effectively reduce mortality.Carboxylesterase(CE)-specific detection and imaging can be used for early diagnosis and image-guided surgical of HCC.However,traditional optical probes suffer from poor selectivity and low imaging signal-to-noise ratio.Here,we have constructed a series of chemiluminescent probes for carboxylesterase detection based on the strategy of enzymatic pocket-oriented steric tailoring techniques.The probes with different unique and excellent properties have been obtained through the structure-based steric hindrance adjustment on the recognition site.Here,CE-2 has been successfully used for high-throughput screening of rapid carboxylesterase inhibitors due to its extremely low detection limit(2.5×10^(-4)U mL^(-1))and fast recognition ability.CE-3 has been successfully used for image-guided surgery of orthotopic hepatocellular carcinoma due to its ultra-long chemiluminescence imaging(over 12 h)of hepatocellular carcinoma.This study may promote advances in the rapid detection and screening of inhibitory drugs for CE and the field of surgical navigation in HCC.
