Plants play a crucial role in maintaining ecological balance and biodiversity.However,plant health is easily affected by environmental stresses.Hence,the rapid and precise monitoring of plant health is crucial for glo...Plants play a crucial role in maintaining ecological balance and biodiversity.However,plant health is easily affected by environmental stresses.Hence,the rapid and precise monitoring of plant health is crucial for global food security and ecological balance.Currently,traditional detection strategies for monitoring plant health mainly rely on expensive equipment and complex operational procedures,which limit their widespread application.Fortunately,near-infrared(NIR)fluorescence and surface-enhanced Raman scattering(SERS)techniques have been recently highlighted in plants.NIR fluorescence imaging holds the advantages of being non-invasive,high-resolution and real-time,which is suitable for rapid screening in large-scale scenarios.While SERS enables highly sensitive and specific detection of trace chemical substances within plant tissues.Therefore,the complementarity of NIR fluorescence and SERS modalities can provide more comprehensive and accurate information for plant disease diagnosis and growth status monitoring.This article summarizes these two modalities in plant applications,and discusses the advantages of multimodal NIR fluorescence/SERS for a better understanding of a plant’s response to stress,thereby improving the accuracy and sensitivity of detection.展开更多
Cancer is a serious global health issue,and exploring effective treatment methods is of great significance for cancer prevention and control.Carbon monoxide(CO),as an important gas signaling molecule in the life syste...Cancer is a serious global health issue,and exploring effective treatment methods is of great significance for cancer prevention and control.Carbon monoxide(CO),as an important gas signaling molecule in the life system,has been proven to have good anti-cancer effects.However,how to controllably,safely,and effectively deliver CO to the tumor site for clinical treatment remains a challenge.Herein,a new metal-free CO-releasing molecule COR-XAC was developed for controlling CO release and cancer therapy.COR-XAC is based on the hybrid of 3-hydroxyl flavone and oxanthracene fluorophores,showing visible light-controlled CO-releasing properties and near-infrared(NIR)ratiometric fluorescence changes at 690 and 760 nm.COR-XAC shows low cytotoxicity and can be successfully applied to release CO in cells and tumors,and the CO-releasing and delivery process could be monitored by its own NIR ratiometric fluorescence changes.More importantly,the anti-cancer performance of COR-XAC was evaluated in 4T1 tumor mice,and it was found that COR-XAC plus light illumination showed excellent tumor inhibition effect,which provided a promising new effective method for cancer treatment.展开更多
A series of near-infrared(NIR)fluorescent substrates(NDRO-1∼8)derived from fluorophore NDRH with different volumes of ester bond as the recognition group were designed and synthesized for the detection of acetylcholi...A series of near-infrared(NIR)fluorescent substrates(NDRO-1∼8)derived from fluorophore NDRH with different volumes of ester bond as the recognition group were designed and synthesized for the detection of acetylcholinesterase(AChE),among which NDRO-1 with the smallest acetate group displayed the highest activity toward AChE.The detection limit of NDRO-1 for sensing AChE was 0.32μg/mL,and K_(m )was 6.40μmol/L,indicating ultra-sensitivity and good affinity of NDRO-1 toward AChE.NDRO-1 was used to detect the inhibitory of four kinds of pesticides including methamidophos,dichlorvos,and the detection limit was lower than 50μg/L,which was further used in pesticide residues detection.展开更多
The role of point-of-care(POC)diagnostics is important in public health.With the support of smartphones,POC diagnostic technologies can be greatly improved.This opportunity has arisen from not only the large number an...The role of point-of-care(POC)diagnostics is important in public health.With the support of smartphones,POC diagnostic technologies can be greatly improved.This opportunity has arisen from not only the large number and fast spread of cell-phones across the world but also their improved imaging/diagnostic functions.As a tool,the smartphone is regarded as part of a compact,portable,and low-cost system for real-time POC,even in areas with few resources.By combining near-infrared(NIR)imaging,measurement,and spectroscopy techniques,pathogens can be detected with high sensitivity.The whole process is rapid,accurate,and low-cost,and will set the future trend for POC diagnostics.In this review,the development of smartphone-based NIR fluorescent imaging technology was described,and the quality and potential of POC applications were discussed.展开更多
Semiconducting polymer nanoparticles(SPNs)have shown great promise in second near-infrared window(NIR-II)phototheranostics.However,the issue of long metabolic time significantly restricts the clinical application of S...Semiconducting polymer nanoparticles(SPNs)have shown great promise in second near-infrared window(NIR-II)phototheranostics.However,the issue of long metabolic time significantly restricts the clinical application of SPNs.In this study,we rationally designed a biodegradable SPN(BSPN50)for NIR-II fluorescence imaging-guided photodynamic therapy(PDT).BSPN50 is prepared by encapsulating a biodegradable SP(BSP50)with an amphiphilic copolymer F-127.BSP50 is composed of NIR-II fluorescent diketopyrrolopyrrole(DPP)segment and degradable poly(phenylenevinylene)(PPV)segment with the ratio of 50/50.BSPN50 has both satisfactory degradability under myeloperoxidase(MPO)/hydrogen peroxide(H_(2)O_(2))and NIR-II fluorescence emission upon 808 nm laser excitation.Furthermore,BSPN50 shows good photodynamic efficacy under 808 nm laser irradiation.BSPN50 shows a faster degradation rate than BSPN100 which has no PPV segment both in vitro and in vivo.In addition,BSPN50 can effectively diagnose tumor via NIR-II fluorescence imaging and inhibit the tumor growth by PDT.Thus,our study provides a rational approach to construct biodegradable nanoplatforms for efficient tumor NIR-II phototheranostics.展开更多
Tuberculosis(TB)is a chronic infectious disease,which is caused by the pathogen Mycobacterium tuberculosis(Mtb)and reemerged as a global health risk with a significant proportion of multi-drug resistant and extensivel...Tuberculosis(TB)is a chronic infectious disease,which is caused by the pathogen Mycobacterium tuberculosis(Mtb)and reemerged as a global health risk with a significant proportion of multi-drug resistant and extensively drug resistant TB cases.It is very urgent to find some novel high-confidence drug targets in Mtb for discovering the effective anti-TB agents.Thioredoxin reductase(TrxR)has been identified to be a highly viable target for anti-TB drugs for its important role in protecting the pathogen from thiol-specific oxidizing stress,regulating intracellular dithiol/disulfide homeostasis and DNA replication and repair.In the present work,a near-infrared(NIR)fluorescent probe DDAT was developed for the detection of TrxR activity and used to high-throughput screen the TrxR inhibitors from natural products.Two screened TrxR inhibitors from Sappan Lignum and microbial metabolites that were further used to inhibit Mycobacterium tuberculosis.All the results indicate that DDAT is a practical fluorescent molecular tool for the discovery of potential anti-TB drugs.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
A novel D–π –A structure and near–infrared fluorescent probe(DCITT) with high polarity sensitivity and membrane targeting was reported. The fluorescent spectra of DCITT were polarity dependent and Stokes shift was...A novel D–π –A structure and near–infrared fluorescent probe(DCITT) with high polarity sensitivity and membrane targeting was reported. The fluorescent spectra of DCITT were polarity dependent and Stokes shift was greater than 300 nm. Due to its high fluorescence quantum yield, low cytotoxicity and photostability, DCITT could be used as a labeling probe in multicellular organisms. In particular, DCITT effectively distinguished tumor cells from normal cells because it could specifically light up the cancer cells membrane based on strong red fluorescence for a long time. On this basis, a polar–sensitive cell membrane probe is developed to differentiate tumor cells from normal cells, which provides an idea and method for the early diagnosis of tumor at cellular level.展开更多
Endoplasmic reticulum(ER)viscosity has emerged as a new potential biomarker for hepatic fibrosis(HF).Herein,we report the first ER-targeting viscosity-responsive near-infrared(NIR)fluorescent probe HBT-PP for investig...Endoplasmic reticulum(ER)viscosity has emerged as a new potential biomarker for hepatic fibrosis(HF).Herein,we report the first ER-targeting viscosity-responsive near-infrared(NIR)fluorescent probe HBT-PP for investigations of HF pathogenesis.The twisted intramolecular charge transfer(TICT)and the excited state intramolecular proton transfer(ESIPT)are combined to endow HBT-PP with the selective response towards viscosity(~62-fold)and a super large stokes shift(~320 nm).HBT-PP mainly targets organelle ER and is able to image the drug-or alcohol-induced viscosity elevation in living cells.Significantly,HBT-PP was successfully applied to visualize the gender difference in HF and the protective role of estrogen in restraining HF progression.Of note,after 10 min of stain with HBT-PP,HF lesions showed a stage-based response,indicating the potential of this probe in fast and early diagnosis of HF.These results clearly demonstrated the promising application of HBT-PP as a new tool for exploring ER viscosity-involved physiological and pathological processes.展开更多
Importance:Fluorescence-guided surgery(FGS)is a potentially powerful tool for hepatobiliary(HPB)surgery.The high sensitivity of fluorescence navigation is especially useful in settings where tactile feedback is limite...Importance:Fluorescence-guided surgery(FGS)is a potentially powerful tool for hepatobiliary(HPB)surgery.The high sensitivity of fluorescence navigation is especially useful in settings where tactile feedback is limited.Objective:The present narrative review evaluates literature on the use of FDA-approved fluorophores such as methylene blue(MB),5-aminolevulinic acid(5-ALA),and indocyanine green(ICG)for clinical intra-operative image-guidance during HPB surgery.Evidence Review:Approaches such as dosing,timing,imaging devices and comparative endpoints are summarized.The feasibility and safety of fluorophores in visualizing the biliary tree,identify biliary leaks,outline anatomic hepatic segments,identify tumors,and evaluate perfusion and graft function in liver transplants are discussed.Findings:Tumor-specific probes are a promising advancement in FGS with a greater degree of specificity.The current status of tumor-specific probes being evaluated in clinical trials are summarized.Conclusions and Relevance for Reviews:Relevant discussion of promising tumor-specific probes in pre-clinical development are discussed.Fluorescence-guidance in HPB surgery is relatively new,but current literature shows that the dyes are reliably able to outline desired structures with a variety of dosing,timing,and imaging devices to provide real-time intra-operative anatomic information to surgeons.Development of tumor-specific probes will further advance the field of HPB surgery especially during oncologic resections.展开更多
One of the thorny problems currently impeding the applications of the fluorescence imaging technique is the poor spatial resolution in deep tissue.Ultrasound-switchable fluorescence(USF)imaging is a novel imaging tool...One of the thorny problems currently impeding the applications of the fluorescence imaging technique is the poor spatial resolution in deep tissue.Ultrasound-switchable fluorescence(USF)imaging is a novel imaging tool that has recently been explored to possibly surmount the above-mentioned bottleneck.Herein,αβ-cyclodextrin/indocyanine green(ICG)complex-encapsulated poly(N-isopropylacrylamide)(PNIPAM)nanogel was synthesized and studied for ex vivo/in vivo deep tissue/high-resolution near infrared USF(NIR-USF)imaging.To be specific,our results revealed that the average diameter of the as-prepared nanogels was significantly decreased to-32 nm from-335 nm compared to the reported ICG-PNIPAM nanoparticles.Additionally,the excitation/emission characteristics of the ICG itself in present nanogels were almost completely retained,and the resultant nanogel exhibited high physiological stability and positive biocompatibility.In particular,the signal-to-noise ratio of the USF image for the PNIPAM/P-cyclodextrin/ICG nanogel(33.01±2.42 dB)was prominently higher than that of the ICG-PNIPAM nanoparticles(18.73±0.33 dB)in 1.5-cm-thick chicken breast tissues.The NIR-USF imaging in 3.5-cm-thick chicken breast tissues was achieved using this new probe.The e x v iv o NIR-USF imaging of the mouse liver was also successfully obtained.Animal experiments showed that the present nanogels were able to be effectively accumulated into U87 tumor-bearing mice via enhanced permeability and retention effects,and the high-resolution NIR-USF imaging of in v ivo tumor was efficiently acquired.The metabolism and in vivo biodistribution of the nanogels were evaluated.Overall,the results suggest that the current nanogel is a highly promising NIR-USF probe for deep tissue and high-resolution USF imaging.展开更多
Biothiols, such as cysteine(Cys) and homocysteine(Hcy), play vital roles in biological homeostasis and are closely related to various pathological and physiological processes in the living systems. Therefore, the in v...Biothiols, such as cysteine(Cys) and homocysteine(Hcy), play vital roles in biological homeostasis and are closely related to various pathological and physiological processes in the living systems. Therefore, the in vivo detection of biothiols is of great importance for early diagnosis of diseases and assessment of disease progression. In this work, we developed a near-infrared(NIR) fluorescence and photoacoustic dual-modal molecular probe(NIR-S) that can be specifically activated by Cys or Hcy. The aryl-thioether substituted cyanine probe can undergo nucleophilic substitution and Smiles rearrangement reaction, resulting in specific turn-on NIR fluorescence and ratiometric photoacoustic responses for Hcy/Cys. Thus, NIR-S not only realizes the specific NIR fluorescence and photoacoustic dual mode imaging to detect Hcy/Cys in solution, but also can be applied to living cells and mice to detect Hcy/Cys. This work provided a practical tool to detect Hcy/Cys levels in vivo, which would be beneficial for the early diagnosis and progress of diseases.展开更多
Identification of fluorescent biomarkers with peptide ligand-directed receptors for diagnosis or theranostic of pancreatic ductal adenocarcinoma (PDAC) is still challenging. As potential prognostic/predictive bioimagi...Identification of fluorescent biomarkers with peptide ligand-directed receptors for diagnosis or theranostic of pancreatic ductal adenocarcinoma (PDAC) is still challenging. As potential prognostic/predictive bioimaging targets, both aminopeptidase N(APN, known as CD13) and Caveolin-1 are found as upregulation on the cell membrane surface of PDAC, in which APN is the principal receptor of the cyclic peptide cNGR (Asn-Gly-Arg, NGR) and Caveolin-1 can synergistically mediate endocytosis in this receptor-targeted process. Herein, we conjugate cNGR to dicyanomethylene-4H-pyran (DCM) chromophore to develop a synergistic-targeted near-infrared (NIR) fluorescent probe DCM-cNGR with strongly intrinsic NIR fluorescence, stable optical performance, low cytotoxicity, and rapid accumulation in PANC-1 cells with the synergistic overexpressed APN receptor-targeted and Caveolin-1-mediated endocytosis. As demonstrated, DCM-cNGR can realize noninvasive NIR imaging for targeting PANC-1 tumor in vivo after intravenous injection into PANC-1 xenograft tumor of nude mice, making a great promise to improve the precision diagnosis and therapy of pancreatic cancer with real time tracing and bioimaging of PDAC in vitro and in vivo.展开更多
Vanin-1 is an amidohydrolase that catalyses the conversion of pantetheine into the aminothiol cysteamine and pantothenic acid(coenzyme A precursor), which plays a vital role in multiple physiological and pathological ...Vanin-1 is an amidohydrolase that catalyses the conversion of pantetheine into the aminothiol cysteamine and pantothenic acid(coenzyme A precursor), which plays a vital role in multiple physiological and pathological processes. In this study, an enzyme-activated near-infrared(NIR) fluorescent probe(DDAV) has been constructed for sensitively detecting Vanin-1 activity in complicated biosamples on the basis of its catalytic characteristics. DDAV exhibited a high selectivity and sensitivity toward Vanin-1 and was successfully applied to the early diagnosis of kidney injury in cisplatin-induced kidney injury model. In addition, DDAV could serve as a visual tool for in situ imaging endogenous Vanin-1 in vivo. More importantly, Enterococcus faecalis 20247 which possessed high expression of Vanin-1 was screened out from intestinal bacteria using DDAV, provided useful guidance for the rational use of NSAIDs in clinic. Finally, oleuropein as a potent natural inhibitor for Vanin-1 was discovered fromherbal medicines library using a high-throughput screening method using DDAV, which held great promise for clinical therapy of inflammatory bowel disease.展开更多
Detection and imaging of α-L-fucosidase(AFU)is of great value to understand its roles in hepatocellular carcinoma(HCC)and tumor early diagnosis,but ideal assays are still lacking.Herein,a near-infrared(NIR)fluorescen...Detection and imaging of α-L-fucosidase(AFU)is of great value to understand its roles in hepatocellular carcinoma(HCC)and tumor early diagnosis,but ideal assays are still lacking.Herein,a near-infrared(NIR)fluorescent biosensor(α-Fuc-DCM)was elaborately designed and synthesized for rapid and ratiometric detection of AFU activity in cells and HCC tumor mouse models.In the presence of AFU,this biosensor shows an enhancement in NIR emission in a ratiometric manner,which significantly improves the detection accuracy with the limit of detection as low as 4.8 mU/mL.Taking advantage of these merits,the activity of AFU in lysosomes could be visualized using ratiometric and NIR dual modality in living cells.Furthermore,its remarkable application for monitoring of endogenous AFU activity in HCC tumor-bearing mouse model is also demonstrated with bright fluorescence signal,which indicated that the biosensor could clearly monitor the liver tumor in the early stage.Importantly,the α-Fuc-DCM probe can be utilized to detect the AFU in serum from HCC patients.This strategy offers a promising biosensor system for early diagnosis of HCC and studying the roles of AFU in cancers.展开更多
Hydrogen peroxide and polarity are closely related to many physiological activities and pathological processes.However,near-infrared fluorescent probes that are sensitive to both H_(2)O_(2)and polarity are still scarc...Hydrogen peroxide and polarity are closely related to many physiological activities and pathological processes.However,near-infrared fluorescent probes that are sensitive to both H_(2)O_(2)and polarity are still scarce.Herein,we developed the first dual-channel near-infrared fluorescent probe NBO,with an AIE effect,enabling simultaneous monitoring of H_(2)O_(2)and polarity.The probe presented high sensitivity,high selectivity,and low detection limit for H_(2)O_(2).It also had high sensitivity to polarity,independent of pH and viscosity,with large Stokes shifts,good photostability,and low cytotoxicity.Moreover,NBO was able to detect both endogenous and exogenous H_(2)O_(2)as well as polarity fluctuations in vivo as a method to effectively differentiate between cancer cells and normal cells.Importantly,it also could monitor the therapeutic effects of drugs in inflammation and iron-dead cells and mice.Based on NIR emission,NBO could be used as an imaging tool and a way to evaluate the therapeutic effect of drugs for inflammation and ferroptosis.展开更多
Fluorescence imaging is a non-invasive and highly sensitive bioimaging technique that has shown remarkable strides in plant science. It enables real-time monitoring and analysis of biological and pathological processe...Fluorescence imaging is a non-invasive and highly sensitive bioimaging technique that has shown remarkable strides in plant science. It enables real-time monitoring and analysis of biological and pathological processes in plants by labeling specific molecular or cellular structures with fluorescent probes. However, tissue scattering and phytochrome interference have been obstacles for conventional fluorescence imaging of plants in the ultraviolet and visible spectrum, resulting in unsatisfactory imaging quality. Fortunately, advances in near-infrared(NIR) fluorescence imaging technology(650-900 nm) offer superior spatial-temporal resolution and reduced tissue scattering, which is sure to improve plant imaging quality. In this review, we summarize recent progress in the development of NIR fluorescence imaging probes and their applications for in vivo plant imaging and the identification of plant-related biomolecules. We hope this review provides a new perspective for plant science research and highlights NIR fluorescence imaging as a powerful tool for analyzing plant physiology, adaptive mechanisms, and coping with environmental stress in the near future.展开更多
Multiple signaling molecules work together in mitochondria to mediate complex physiological processes.However,most current fluorescent probes lack of ability to clarify the function of these actives in mitochondria du...Multiple signaling molecules work together in mitochondria to mediate complex physiological processes.However,most current fluorescent probes lack of ability to clarify the function of these actives in mitochondria due to their non-specific binding with analytes outside mitochondria.In this study,we designed an on-demand light-activated mitochondria-targeted fluorescent probe to observe in situ fluctuations in mitochondrial esterase.The designed probe has a natural yellow fluorescence that monitors entry into the mitochondria and maintains nonfluorescent responsiveness to esterase during cellular delivery.Following the enrichment of the probe in mitochondria,on-demand photoactivation only at the required mitochondrial location resulted in a remarkable emission response to the esterase with red fluorescence at 700 nm.Precise spatiotemporal recognition of esterase in mitochondria is successfully achieved by activating the in situ fluorescence response of esterase by light irradiation.This work provides a new strategy for the study of esterase-related diseases.展开更多
Precise and early detection ofβ-amyloid(Aβ)deposits in situ and in real time is pivotal to the diagnosis and early intervention of Alzheimer’s disease(AD).Optical imaging stands out to be a promising technique for ...Precise and early detection ofβ-amyloid(Aβ)deposits in situ and in real time is pivotal to the diagnosis and early intervention of Alzheimer’s disease(AD).Optical imaging stands out to be a promising technique for such a task;however,it still remains a big challenge,due to the lack of high-performance imaging contrast agent.Restricted by poor blood-brain barrier(BBB)penetrability,short-wavelength excitation and emission,as well as the aggregation-caused quenching effect,the widely used goldstandard probes cannot be used for early in-vivo imaging of Aβdeposits.Herein,we integrate the Aβdeposits-favored geometry,amphiphilic and zwitterionic molecular structure,extended D-π-A electronic structure,and 3 D conformation into one molecule,facilely establishing a simple and economic imaging contrast agent that enjoys high specificity and affinity to Aβdeposits,good BBB penetrability,bright red/near-infrared fluorescence,low interference from autofluorescence,aggregation-induced emission(AIE)feature,high signal-to-noise ratio(SNR),and high contrast.In-vitro,ex-vivo,and in-vivo experiments with different strains of mice indicate that AIE-CNPy-AD holds the universality to Aβdeposits identification.Noteworthily,AIE-CNPy-AD is even able to precisely trace the small and sparsely-distributed Aβdeposits in AD model mice as young as 4-month-old APP/PS1 mice,the youngest having Aβdeposits.Moreover,the present probe could clearly reveal the increase and enlargement of Aβdeposits as the mice grow.Therefore,AIE-CNPy-AD might be an ideal alternative for early AD diagnosis and highly reliable monitoring of AD progression.展开更多
Milk-derived exosomes are widely used for diagnosis,delivery,imaging,and theranostic applications.Near-Infrared(NIR)based fluorescence bioimaging is an attractive and safer technique that is used for clinical applicat...Milk-derived exosomes are widely used for diagnosis,delivery,imaging,and theranostic applications.Near-Infrared(NIR)based fluorescence bioimaging is an attractive and safer technique that is used for clinical applications.However,almost all NIR imaging agents tend to have poor photostability,short half-life,nonspecific protein binding,and concentrationdependent aggregation(s).Therefore,there is an unmet clinical need to develop newer and safer modalities to package and deliver NIR imaging agents.Bovine milk exosomes are natural,biocompatible,safe,and efficient nanocarriers that facilitate the delivery of micro-and macromolecules.Herein,we developed an exosome-based NIR dye loaded nanoimaging formulation that offers improved solubility and photostability of NIR dye.Following the acetic acid based extracellular vesicle(EV)treatment method,we extracted the bovine milk exosomes from a variety of pasteurized grade milk.The EVs were screened for their physicochemical properties such as particle size and concentration and zeta potential.The stability of these exosomes was also determined under different conditions,including storage temperatures,pH,and salt concentrations.Next,indocyanine green,a model NIR dye was loaded into these exosomes(Exo-Glow)via a sonication method and further assessed for their improved fluorescence intensity and photostability using an IVIS imaging system.Initial screening suggested that size of the selected bovine milk exosomes was∼100−135 nm with an average particle concentration of 5.8×10^(2)particles/mL.Exo-Glow further demonstrated higher fluorescence intensity in cancer cells and tissues when compared to free dye.These results showed that Exo-Glow has the potential to serve as a safer NIR imaging tool for cancer cells/tissues.展开更多
基金funded by the National Natural Science Foundation of China(Nos.22374055,22022404,22074050,82172055)the National Natural Science Foundation of Hubei Province(No.22022CFA033)the Fundamental Research Funds for the Central Universities(Nos.CCNU24JCPT001,CCNU24JCPT020)。
文摘Plants play a crucial role in maintaining ecological balance and biodiversity.However,plant health is easily affected by environmental stresses.Hence,the rapid and precise monitoring of plant health is crucial for global food security and ecological balance.Currently,traditional detection strategies for monitoring plant health mainly rely on expensive equipment and complex operational procedures,which limit their widespread application.Fortunately,near-infrared(NIR)fluorescence and surface-enhanced Raman scattering(SERS)techniques have been recently highlighted in plants.NIR fluorescence imaging holds the advantages of being non-invasive,high-resolution and real-time,which is suitable for rapid screening in large-scale scenarios.While SERS enables highly sensitive and specific detection of trace chemical substances within plant tissues.Therefore,the complementarity of NIR fluorescence and SERS modalities can provide more comprehensive and accurate information for plant disease diagnosis and growth status monitoring.This article summarizes these two modalities in plant applications,and discusses the advantages of multimodal NIR fluorescence/SERS for a better understanding of a plant’s response to stress,thereby improving the accuracy and sensitivity of detection.
基金supported by the National Natural Science Foundation of China(Nos.22077044 and 21672080)the Natural Science Foundation of Hubei Province(No.2022CFA033)the funding from Wuhan Institute of Photochemistry and Technology(No.GHY2023KF008).
文摘Cancer is a serious global health issue,and exploring effective treatment methods is of great significance for cancer prevention and control.Carbon monoxide(CO),as an important gas signaling molecule in the life system,has been proven to have good anti-cancer effects.However,how to controllably,safely,and effectively deliver CO to the tumor site for clinical treatment remains a challenge.Herein,a new metal-free CO-releasing molecule COR-XAC was developed for controlling CO release and cancer therapy.COR-XAC is based on the hybrid of 3-hydroxyl flavone and oxanthracene fluorophores,showing visible light-controlled CO-releasing properties and near-infrared(NIR)ratiometric fluorescence changes at 690 and 760 nm.COR-XAC shows low cytotoxicity and can be successfully applied to release CO in cells and tumors,and the CO-releasing and delivery process could be monitored by its own NIR ratiometric fluorescence changes.More importantly,the anti-cancer performance of COR-XAC was evaluated in 4T1 tumor mice,and it was found that COR-XAC plus light illumination showed excellent tumor inhibition effect,which provided a promising new effective method for cancer treatment.
基金supported financially by National Key R&D Program of China (No. 2018YFC1603001)
文摘A series of near-infrared(NIR)fluorescent substrates(NDRO-1∼8)derived from fluorophore NDRH with different volumes of ester bond as the recognition group were designed and synthesized for the detection of acetylcholinesterase(AChE),among which NDRO-1 with the smallest acetate group displayed the highest activity toward AChE.The detection limit of NDRO-1 for sensing AChE was 0.32μg/mL,and K_(m )was 6.40μmol/L,indicating ultra-sensitivity and good affinity of NDRO-1 toward AChE.NDRO-1 was used to detect the inhibitory of four kinds of pesticides including methamidophos,dichlorvos,and the detection limit was lower than 50μg/L,which was further used in pesticide residues detection.
基金supported by the National Natural Science Foundation of China(No.81773352)the China Scholarship Council(No.201703170071)。
文摘The role of point-of-care(POC)diagnostics is important in public health.With the support of smartphones,POC diagnostic technologies can be greatly improved.This opportunity has arisen from not only the large number and fast spread of cell-phones across the world but also their improved imaging/diagnostic functions.As a tool,the smartphone is regarded as part of a compact,portable,and low-cost system for real-time POC,even in areas with few resources.By combining near-infrared(NIR)imaging,measurement,and spectroscopy techniques,pathogens can be detected with high sensitivity.The whole process is rapid,accurate,and low-cost,and will set the future trend for POC diagnostics.In this review,the development of smartphone-based NIR fluorescent imaging technology was described,and the quality and potential of POC applications were discussed.
基金the National Natural Science Foundation of China(Nos.22174070 and 22205115)Natural Science Foundation of Jiangsu Province(No.BK20230060)+4 种基金Natural Science Foundation of Jiangsu University(No.21KJB150022)the Research startup fund of NJUPT(No.NY220149)Natural Science Foundation of NJUPT(No.NY221088)the Project of State Key Laboratory of Organic Electronics and Information Displays,Nanjing University of Posts and Telecommunications(Nos.GZR2022010012 and GZR2023010022)the Synergetic Innovation Center for Organic Electronics and Information Displays for the financial support.
文摘Semiconducting polymer nanoparticles(SPNs)have shown great promise in second near-infrared window(NIR-II)phototheranostics.However,the issue of long metabolic time significantly restricts the clinical application of SPNs.In this study,we rationally designed a biodegradable SPN(BSPN50)for NIR-II fluorescence imaging-guided photodynamic therapy(PDT).BSPN50 is prepared by encapsulating a biodegradable SP(BSP50)with an amphiphilic copolymer F-127.BSP50 is composed of NIR-II fluorescent diketopyrrolopyrrole(DPP)segment and degradable poly(phenylenevinylene)(PPV)segment with the ratio of 50/50.BSPN50 has both satisfactory degradability under myeloperoxidase(MPO)/hydrogen peroxide(H_(2)O_(2))and NIR-II fluorescence emission upon 808 nm laser excitation.Furthermore,BSPN50 shows good photodynamic efficacy under 808 nm laser irradiation.BSPN50 shows a faster degradation rate than BSPN100 which has no PPV segment both in vitro and in vivo.In addition,BSPN50 can effectively diagnose tumor via NIR-II fluorescence imaging and inhibit the tumor growth by PDT.Thus,our study provides a rational approach to construct biodegradable nanoplatforms for efficient tumor NIR-II phototheranostics.
基金the National Natural Science Foundation of China(Nos.81930112 and 82225048)Open Research Fund of the School of Chemistry and Chemical Engineering,Henan Normal University for support(No.2021YB07)Research on National Reference Material and Product Development of Natural Products(No.SG030801,Beijing Polytechnic)。
文摘Tuberculosis(TB)is a chronic infectious disease,which is caused by the pathogen Mycobacterium tuberculosis(Mtb)and reemerged as a global health risk with a significant proportion of multi-drug resistant and extensively drug resistant TB cases.It is very urgent to find some novel high-confidence drug targets in Mtb for discovering the effective anti-TB agents.Thioredoxin reductase(TrxR)has been identified to be a highly viable target for anti-TB drugs for its important role in protecting the pathogen from thiol-specific oxidizing stress,regulating intracellular dithiol/disulfide homeostasis and DNA replication and repair.In the present work,a near-infrared(NIR)fluorescent probe DDAT was developed for the detection of TrxR activity and used to high-throughput screen the TrxR inhibitors from natural products.Two screened TrxR inhibitors from Sappan Lignum and microbial metabolites that were further used to inhibit Mycobacterium tuberculosis.All the results indicate that DDAT is a practical fluorescent molecular tool for the discovery of potential anti-TB drugs.
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Henan Provincial Science and Technology Research Project (No.232102310369) for financial support。
文摘A novel D–π –A structure and near–infrared fluorescent probe(DCITT) with high polarity sensitivity and membrane targeting was reported. The fluorescent spectra of DCITT were polarity dependent and Stokes shift was greater than 300 nm. Due to its high fluorescence quantum yield, low cytotoxicity and photostability, DCITT could be used as a labeling probe in multicellular organisms. In particular, DCITT effectively distinguished tumor cells from normal cells because it could specifically light up the cancer cells membrane based on strong red fluorescence for a long time. On this basis, a polar–sensitive cell membrane probe is developed to differentiate tumor cells from normal cells, which provides an idea and method for the early diagnosis of tumor at cellular level.
基金supported by the National Natural Science Foundation of China(22338005,22208045,2192580,U23A20489)the Liaoning Binhai Laboratory(LBLB-2023-03)+2 种基金the Fundamental Research Funds for the Central Universities(DUT22LAB60)the Zhejiang Provincial Natural Science Foundation(TGY24B060002)the Ningbo Natural Science Foundation(2022J012,2023S115)。
文摘Endoplasmic reticulum(ER)viscosity has emerged as a new potential biomarker for hepatic fibrosis(HF).Herein,we report the first ER-targeting viscosity-responsive near-infrared(NIR)fluorescent probe HBT-PP for investigations of HF pathogenesis.The twisted intramolecular charge transfer(TICT)and the excited state intramolecular proton transfer(ESIPT)are combined to endow HBT-PP with the selective response towards viscosity(~62-fold)and a super large stokes shift(~320 nm).HBT-PP mainly targets organelle ER and is able to image the drug-or alcohol-induced viscosity elevation in living cells.Significantly,HBT-PP was successfully applied to visualize the gender difference in HF and the protective role of estrogen in restraining HF progression.Of note,after 10 min of stain with HBT-PP,HF lesions showed a stage-based response,indicating the potential of this probe in fast and early diagnosis of HF.These results clearly demonstrated the promising application of HBT-PP as a new tool for exploring ER viscosity-involved physiological and pathological processes.
基金This work was supported by US National Cancer Institute grant numbers CA126023,CA142669(MB and AntiCancer,Inc.)VA Merit Review grant number 1 I01 BX003856-01A1(MB)NIH/NCI T32CA121938(TM Lwin).
文摘Importance:Fluorescence-guided surgery(FGS)is a potentially powerful tool for hepatobiliary(HPB)surgery.The high sensitivity of fluorescence navigation is especially useful in settings where tactile feedback is limited.Objective:The present narrative review evaluates literature on the use of FDA-approved fluorophores such as methylene blue(MB),5-aminolevulinic acid(5-ALA),and indocyanine green(ICG)for clinical intra-operative image-guidance during HPB surgery.Evidence Review:Approaches such as dosing,timing,imaging devices and comparative endpoints are summarized.The feasibility and safety of fluorophores in visualizing the biliary tree,identify biliary leaks,outline anatomic hepatic segments,identify tumors,and evaluate perfusion and graft function in liver transplants are discussed.Findings:Tumor-specific probes are a promising advancement in FGS with a greater degree of specificity.The current status of tumor-specific probes being evaluated in clinical trials are summarized.Conclusions and Relevance for Reviews:Relevant discussion of promising tumor-specific probes in pre-clinical development are discussed.Fluorescence-guidance in HPB surgery is relatively new,but current literature shows that the dyes are reliably able to outline desired structures with a variety of dosing,timing,and imaging devices to provide real-time intra-operative anatomic information to surgeons.Development of tumor-specific probes will further advance the field of HPB surgery especially during oncologic resections.
基金This work was supported in part by funding from the CPRIT RP170564(Baohong Yuan)and the NSF CBET-1253199(Baohong Yuan).
文摘One of the thorny problems currently impeding the applications of the fluorescence imaging technique is the poor spatial resolution in deep tissue.Ultrasound-switchable fluorescence(USF)imaging is a novel imaging tool that has recently been explored to possibly surmount the above-mentioned bottleneck.Herein,αβ-cyclodextrin/indocyanine green(ICG)complex-encapsulated poly(N-isopropylacrylamide)(PNIPAM)nanogel was synthesized and studied for ex vivo/in vivo deep tissue/high-resolution near infrared USF(NIR-USF)imaging.To be specific,our results revealed that the average diameter of the as-prepared nanogels was significantly decreased to-32 nm from-335 nm compared to the reported ICG-PNIPAM nanoparticles.Additionally,the excitation/emission characteristics of the ICG itself in present nanogels were almost completely retained,and the resultant nanogel exhibited high physiological stability and positive biocompatibility.In particular,the signal-to-noise ratio of the USF image for the PNIPAM/P-cyclodextrin/ICG nanogel(33.01±2.42 dB)was prominently higher than that of the ICG-PNIPAM nanoparticles(18.73±0.33 dB)in 1.5-cm-thick chicken breast tissues.The NIR-USF imaging in 3.5-cm-thick chicken breast tissues was achieved using this new probe.The e x v iv o NIR-USF imaging of the mouse liver was also successfully obtained.Animal experiments showed that the present nanogels were able to be effectively accumulated into U87 tumor-bearing mice via enhanced permeability and retention effects,and the high-resolution NIR-USF imaging of in v ivo tumor was efficiently acquired.The metabolism and in vivo biodistribution of the nanogels were evaluated.Overall,the results suggest that the current nanogel is a highly promising NIR-USF probe for deep tissue and high-resolution USF imaging.
基金supported by the National Natural Science Foundation of China(21907050,21977044,21571099,21731004)the Fundamental Research Funds for the Central Universities(020514380172)+1 种基金the Natural Science Foundation of Jiangsu Province(BK20190282)the National Basic Research Program of China(2015CB856300)。
文摘Biothiols, such as cysteine(Cys) and homocysteine(Hcy), play vital roles in biological homeostasis and are closely related to various pathological and physiological processes in the living systems. Therefore, the in vivo detection of biothiols is of great importance for early diagnosis of diseases and assessment of disease progression. In this work, we developed a near-infrared(NIR) fluorescence and photoacoustic dual-modal molecular probe(NIR-S) that can be specifically activated by Cys or Hcy. The aryl-thioether substituted cyanine probe can undergo nucleophilic substitution and Smiles rearrangement reaction, resulting in specific turn-on NIR fluorescence and ratiometric photoacoustic responses for Hcy/Cys. Thus, NIR-S not only realizes the specific NIR fluorescence and photoacoustic dual mode imaging to detect Hcy/Cys in solution, but also can be applied to living cells and mice to detect Hcy/Cys. This work provided a practical tool to detect Hcy/Cys levels in vivo, which would be beneficial for the early diagnosis and progress of diseases.
基金supported by the National Basic Research Program of China (2013CB733700)the National Natural Science Foundation of China for Creative Research Groups (21421004)+6 种基金Key Project (21636002)Distinguished Young Scholars (21325625)NSFC/Chinathe Oriental ScholarshipScience and Technology Commission of Shanghai Municipality (15XD1501400)the Fundamental Research Funds for the Central Universities (222201717003)Program of Introducing Talents of Discipline to Universities (B16017)
文摘Identification of fluorescent biomarkers with peptide ligand-directed receptors for diagnosis or theranostic of pancreatic ductal adenocarcinoma (PDAC) is still challenging. As potential prognostic/predictive bioimaging targets, both aminopeptidase N(APN, known as CD13) and Caveolin-1 are found as upregulation on the cell membrane surface of PDAC, in which APN is the principal receptor of the cyclic peptide cNGR (Asn-Gly-Arg, NGR) and Caveolin-1 can synergistically mediate endocytosis in this receptor-targeted process. Herein, we conjugate cNGR to dicyanomethylene-4H-pyran (DCM) chromophore to develop a synergistic-targeted near-infrared (NIR) fluorescent probe DCM-cNGR with strongly intrinsic NIR fluorescence, stable optical performance, low cytotoxicity, and rapid accumulation in PANC-1 cells with the synergistic overexpressed APN receptor-targeted and Caveolin-1-mediated endocytosis. As demonstrated, DCM-cNGR can realize noninvasive NIR imaging for targeting PANC-1 tumor in vivo after intravenous injection into PANC-1 xenograft tumor of nude mice, making a great promise to improve the precision diagnosis and therapy of pancreatic cancer with real time tracing and bioimaging of PDAC in vitro and in vivo.
基金financially supported by National Natural Science Foundation of China(Nos.81930112 and 82004211)State Key Laboratory of Fine Chemicals KF1912,Distinguished professor of Liaoning Province,Dalian Science and Technology Leading Talents Project(2019RD15,China)the Open Research Fund of the School of Chemistry and Chemical Engineering,Henan Normal University(2021YB07)。
文摘Vanin-1 is an amidohydrolase that catalyses the conversion of pantetheine into the aminothiol cysteamine and pantothenic acid(coenzyme A precursor), which plays a vital role in multiple physiological and pathological processes. In this study, an enzyme-activated near-infrared(NIR) fluorescent probe(DDAV) has been constructed for sensitively detecting Vanin-1 activity in complicated biosamples on the basis of its catalytic characteristics. DDAV exhibited a high selectivity and sensitivity toward Vanin-1 and was successfully applied to the early diagnosis of kidney injury in cisplatin-induced kidney injury model. In addition, DDAV could serve as a visual tool for in situ imaging endogenous Vanin-1 in vivo. More importantly, Enterococcus faecalis 20247 which possessed high expression of Vanin-1 was screened out from intestinal bacteria using DDAV, provided useful guidance for the rational use of NSAIDs in clinic. Finally, oleuropein as a potent natural inhibitor for Vanin-1 was discovered fromherbal medicines library using a high-throughput screening method using DDAV, which held great promise for clinical therapy of inflammatory bowel disease.
基金National Key R&D Program of China,Grant/Award Number:2017YFE0132200National Natural Science Foundation of China,Grant/Award Numbers:5191160730,51873092,81921004,81802116+3 种基金Natural Science Foundation of Guangdong Province,Grant/Award Number:2021A1515011633Science and Technology Program of Guangzhou,Grant/Award Number:202102020705Outstanding Youths Development Scheme of Nanfang Hospital,Southern Medical University,Grant/Award Number:2018J002Tianjin Science Fund for Distinguished Young Scholars,Grant/Award Number:19JCQJC61200。
文摘Detection and imaging of α-L-fucosidase(AFU)is of great value to understand its roles in hepatocellular carcinoma(HCC)and tumor early diagnosis,but ideal assays are still lacking.Herein,a near-infrared(NIR)fluorescent biosensor(α-Fuc-DCM)was elaborately designed and synthesized for rapid and ratiometric detection of AFU activity in cells and HCC tumor mouse models.In the presence of AFU,this biosensor shows an enhancement in NIR emission in a ratiometric manner,which significantly improves the detection accuracy with the limit of detection as low as 4.8 mU/mL.Taking advantage of these merits,the activity of AFU in lysosomes could be visualized using ratiometric and NIR dual modality in living cells.Furthermore,its remarkable application for monitoring of endogenous AFU activity in HCC tumor-bearing mouse model is also demonstrated with bright fluorescence signal,which indicated that the biosensor could clearly monitor the liver tumor in the early stage.Importantly,the α-Fuc-DCM probe can be utilized to detect the AFU in serum from HCC patients.This strategy offers a promising biosensor system for early diagnosis of HCC and studying the roles of AFU in cancers.
基金support from Scientific and Technological Key Project in Henan Province(22170015)National Natural Science Foundation of China(U1704161,22106061)+1 种基金Zhengzhou University(32211807)Henan Provincial Science and Technology Research Project(JC21253010)。
文摘Hydrogen peroxide and polarity are closely related to many physiological activities and pathological processes.However,near-infrared fluorescent probes that are sensitive to both H_(2)O_(2)and polarity are still scarce.Herein,we developed the first dual-channel near-infrared fluorescent probe NBO,with an AIE effect,enabling simultaneous monitoring of H_(2)O_(2)and polarity.The probe presented high sensitivity,high selectivity,and low detection limit for H_(2)O_(2).It also had high sensitivity to polarity,independent of pH and viscosity,with large Stokes shifts,good photostability,and low cytotoxicity.Moreover,NBO was able to detect both endogenous and exogenous H_(2)O_(2)as well as polarity fluctuations in vivo as a method to effectively differentiate between cancer cells and normal cells.Importantly,it also could monitor the therapeutic effects of drugs in inflammation and iron-dead cells and mice.Based on NIR emission,NBO could be used as an imaging tool and a way to evaluate the therapeutic effect of drugs for inflammation and ferroptosis.
基金supported by the National Natural Science Foundation of China(U20A2038,22022404,21977036,22074050)the CRI Project of National Research Foundation of Republic of Korea(2018R1A3B1052702)+1 种基金Department of Biotechnology,New Delhi,India,for prestigious DBT-Ramalingaswami fellowship(BT/RLF/Re-entry/59/2018)Science&Engineering Research Board,New Delhi(CRG/2021/002476)。
文摘Fluorescence imaging is a non-invasive and highly sensitive bioimaging technique that has shown remarkable strides in plant science. It enables real-time monitoring and analysis of biological and pathological processes in plants by labeling specific molecular or cellular structures with fluorescent probes. However, tissue scattering and phytochrome interference have been obstacles for conventional fluorescence imaging of plants in the ultraviolet and visible spectrum, resulting in unsatisfactory imaging quality. Fortunately, advances in near-infrared(NIR) fluorescence imaging technology(650-900 nm) offer superior spatial-temporal resolution and reduced tissue scattering, which is sure to improve plant imaging quality. In this review, we summarize recent progress in the development of NIR fluorescence imaging probes and their applications for in vivo plant imaging and the identification of plant-related biomolecules. We hope this review provides a new perspective for plant science research and highlights NIR fluorescence imaging as a powerful tool for analyzing plant physiology, adaptive mechanisms, and coping with environmental stress in the near future.
基金supported by the National Natural Science Foundation of China(82173657,22077030,22271092)the support from the Institute of Fudan University-Quzhou。
文摘Multiple signaling molecules work together in mitochondria to mediate complex physiological processes.However,most current fluorescent probes lack of ability to clarify the function of these actives in mitochondria due to their non-specific binding with analytes outside mitochondria.In this study,we designed an on-demand light-activated mitochondria-targeted fluorescent probe to observe in situ fluctuations in mitochondrial esterase.The designed probe has a natural yellow fluorescence that monitors entry into the mitochondria and maintains nonfluorescent responsiveness to esterase during cellular delivery.Following the enrichment of the probe in mitochondria,on-demand photoactivation only at the required mitochondrial location resulted in a remarkable emission response to the esterase with red fluorescence at 700 nm.Precise spatiotemporal recognition of esterase in mitochondria is successfully achieved by activating the in situ fluorescence response of esterase by light irradiation.This work provides a new strategy for the study of esterase-related diseases.
基金supported by the National Natural Science Foundation of China(21788102,21875064,81903545,21604023,21790361)Shanghai Science and Technology Commission Basic Project-Shanghai Natural Science Foundation(21ZR1417600)+5 种基金Shanghai Municipal Science and Technology Major Project(2018SHZDZX03)Programme of Introducing Talents of Discipline to Universities(B16017)Shanghai Science and Technology Committee(17520750100)Beijing New-Star Plan of Science and Technology(Z201100006820009)Shanghai Sailing Program(16YF1402200)the Fundamental Research Funds for the Central Universities。
文摘Precise and early detection ofβ-amyloid(Aβ)deposits in situ and in real time is pivotal to the diagnosis and early intervention of Alzheimer’s disease(AD).Optical imaging stands out to be a promising technique for such a task;however,it still remains a big challenge,due to the lack of high-performance imaging contrast agent.Restricted by poor blood-brain barrier(BBB)penetrability,short-wavelength excitation and emission,as well as the aggregation-caused quenching effect,the widely used goldstandard probes cannot be used for early in-vivo imaging of Aβdeposits.Herein,we integrate the Aβdeposits-favored geometry,amphiphilic and zwitterionic molecular structure,extended D-π-A electronic structure,and 3 D conformation into one molecule,facilely establishing a simple and economic imaging contrast agent that enjoys high specificity and affinity to Aβdeposits,good BBB penetrability,bright red/near-infrared fluorescence,low interference from autofluorescence,aggregation-induced emission(AIE)feature,high signal-to-noise ratio(SNR),and high contrast.In-vitro,ex-vivo,and in-vivo experiments with different strains of mice indicate that AIE-CNPy-AD holds the universality to Aβdeposits identification.Noteworthily,AIE-CNPy-AD is even able to precisely trace the small and sparsely-distributed Aβdeposits in AD model mice as young as 4-month-old APP/PS1 mice,the youngest having Aβdeposits.Moreover,the present probe could clearly reveal the increase and enlargement of Aβdeposits as the mice grow.Therefore,AIE-CNPy-AD might be an ideal alternative for early AD diagnosis and highly reliable monitoring of AD progression.
基金supported by Start-up from Division of Immunology and Microbiology,Medicine and Oncology ISU,School of Medicine,University of Texas Rio Grande Valley and NIH grants(SC1GM139727,R01 CA210192,and R01 CA206069)This research work utilized equipment and services of Integrated Cancer Research Center funded by CPRIT(RP210180 and RP230419)and UT System Star Award.
文摘Milk-derived exosomes are widely used for diagnosis,delivery,imaging,and theranostic applications.Near-Infrared(NIR)based fluorescence bioimaging is an attractive and safer technique that is used for clinical applications.However,almost all NIR imaging agents tend to have poor photostability,short half-life,nonspecific protein binding,and concentrationdependent aggregation(s).Therefore,there is an unmet clinical need to develop newer and safer modalities to package and deliver NIR imaging agents.Bovine milk exosomes are natural,biocompatible,safe,and efficient nanocarriers that facilitate the delivery of micro-and macromolecules.Herein,we developed an exosome-based NIR dye loaded nanoimaging formulation that offers improved solubility and photostability of NIR dye.Following the acetic acid based extracellular vesicle(EV)treatment method,we extracted the bovine milk exosomes from a variety of pasteurized grade milk.The EVs were screened for their physicochemical properties such as particle size and concentration and zeta potential.The stability of these exosomes was also determined under different conditions,including storage temperatures,pH,and salt concentrations.Next,indocyanine green,a model NIR dye was loaded into these exosomes(Exo-Glow)via a sonication method and further assessed for their improved fluorescence intensity and photostability using an IVIS imaging system.Initial screening suggested that size of the selected bovine milk exosomes was∼100−135 nm with an average particle concentration of 5.8×10^(2)particles/mL.Exo-Glow further demonstrated higher fluorescence intensity in cancer cells and tissues when compared to free dye.These results showed that Exo-Glow has the potential to serve as a safer NIR imaging tool for cancer cells/tissues.
