The five-year survival rate for pancreatic cancer is less than 5%. However, the current clinical multimodal therapy combined with first-line chemotherapy drugs only increases the patient’s median survival from 5.0 mo...The five-year survival rate for pancreatic cancer is less than 5%. However, the current clinical multimodal therapy combined with first-line chemotherapy drugs only increases the patient’s median survival from 5.0 months to 7.2 months. Consequently, a new strategy of cancer treatments is urgently needed to overcome this high-fatality disease. Through a series of biometric analyses, we found that KRAS is highly expressed in the tumor of pancreatic cancer patients, and this high expression is closely related to the poor prognosis of patients. It shows that inhibiting the expression of KRAS has great potential in gene therapy for pancreatic cancer. Given those above, we have exploited the possibility of targeted delivery of KRAS shRNA with the intelligent and bio-responsive nanomedicine to detect the special oxidative stress microenvironment of cancer cells and realize efficient cancer theranostics. Our observations demonstrate that by designing the smart self-assembled nanocapsules of melanin with fluorescent nanoclusters we can readily achieve the bio-recognition and bioimaging of cancer cells in biological solution or serum.The self-assembled nanocapsules can make a significant bio-response to the oxidative stress microenvironment of cancer cells and generate fluorescent zinc oxide Nanoclusters in situ for targeted cell bioimaging. Moreover, it can also readily facilitate cancer cell suppression through the targeted delivery of KRAS shRNA and low-temperature hyperthermia. This raises the possibility to provide a promising theranostics platform and self-assembled nanomedicine for targeted cancer diagnostics and treatments through special oxidative stress-responsive effects of cancer cells.展开更多
Subcellular localization of proteins can provide key hints to infer their functions and structures in cells. With the breakthrough of recent molecule imaging techniques, the usage of 2D bioimages has become increasing...Subcellular localization of proteins can provide key hints to infer their functions and structures in cells. With the breakthrough of recent molecule imaging techniques, the usage of 2D bioimages has become increasingly popular in automatically analyzing the protein subcellular location pat- terns. Compared with the widely used protein 1D amino acid sequence data, the images of protein distribution are more intuitive and interpretable, making the images a better choice at many applications for revealing the dynamic char- acteristics of proteins, such as detecting protein translocation and quantification of proteins. In this paper, we systemati- cally reviewed the recent progresses in the field of automated image-based protein subcellular location prediction, and clas- sified them into four categories including growing of bioim- age databases, description of subcellular location distribution patterns, classification methods, and applications of the pre- diction systems. Besides, we also discussed some potential directions in this field.展开更多
Colorectal cancer(CRC)is one of the most prevalent malignant tumors worldwide,exhibiting high morbidity and mortality.Lack of efficient tools for early diagnosis and surgical resection guidance of CRC have been a seri...Colorectal cancer(CRC)is one of the most prevalent malignant tumors worldwide,exhibiting high morbidity and mortality.Lack of efficient tools for early diagnosis and surgical resection guidance of CRC have been a serious threat to the long-term survival rate of the CRC patients.Recent studies have shown that relative higher viscosity was presented in tumor cells compared to that in normal cells,leading to viscosity as a potential biomarker for CRC.Herein,we reported the development of a series of novel viscosity-sensitive and mitochondria-specific fluorescent probes(HTB,HTI,and HTP)for CRC detection.Among them,HTB showed high sensitivity,minimal background interference,low cytotoxicity,and significant viscous response capability,making it an ideal tool for distinguishing colorectal tumor cells from normal cells.Importantly,we have successfully utilized HTB to visualize in a CRC-cells-derived xenograft(CDX)model,enriching its medical imaging capacity,which laid a foundation for further clinical translational application.展开更多
Carbon dots(CDs)are fluorescent carbon-based nanomaterials with sizes smal-ler than 10 nm,that are renowned for their exceptional properties,including superior anti-photobleaching,excellent biocompatibility,and minima...Carbon dots(CDs)are fluorescent carbon-based nanomaterials with sizes smal-ler than 10 nm,that are renowned for their exceptional properties,including superior anti-photobleaching,excellent biocompatibility,and minimal toxicity,which have received sig-nificant interest.Near-infrared(NIR)light has emerged as an ideal light source in the biolo-gical field due to its advantages of minimal scattering and absorption,long wavelength emission,increased tissue penetration,and reduced interference from biological back-grounds.CDs with efficient absorption and/or emission characteristics in the NIR spectrum have shown remarkable promise in the biomedical uses.This study provides a comprehens-ive overview of the preparation methods and wavelength modulation strategies for near-in-frared CDs and reviews research progress in their use in the areas of biosensing,bioimaging,and therapy.It also discusses current challenges and clinical prospects,aimed at deepening our understanding of the subject and promoting further advances in this field.展开更多
Optical imaging in vivo holds significant implications for disease diagnosis, and nanoprobes with near-infrared (NIR) emission leverage the deep tissue penetration and high spatiotemporal resolution provided by NIR li...Optical imaging in vivo holds significant implications for disease diagnosis, and nanoprobes with near-infrared (NIR) emission leverage the deep tissue penetration and high spatiotemporal resolution provided by NIR light, demonstrating considerable application potential. This study presents the design and synthesis of three nitrogen-doped boron–dipyrrin (Aza-BODIPY) molecules: Aza–BDP–OCH_(3), Aza–BDP–OH, and Aza–BDP-I. Leveraging the strong electron-accepting properties of the Aza-BODIPY core, we developed a donor–acceptor–donor (D-A-D) structure for Aza–BDP–OCH_(3) through modifications with triphenylamine and methoxy groups, resulting in NIR fluorescence. Aza–BDP–OH was obtained via demethylation using boron tribromide, whereas Aza–BDP-I was synthesized by introducing iodine into Aza–BDP–OCH_(3). These three molecules self-assemble with the amphiphilic polymer PMHC18-mPEG to form nanoparticles (NPs), yielding optical nanoprobes. The resulting NPs exhibit NIR emission, good water solubility, and biocompatibility. At a concentration of 100 μg·mL^(-1), these NPs demonstrate low biological toxicity, highlighting their potential for biological applications. Following tail vein injection, Aza–BDP-I NPs accumulate in tumors and effectively illuminate them via the enhanced permeability and retention (EPR) effect. Furthermore, these organic NPs were metabolized by the liver. Therefore, Aza-BODIPY-based NIR fluorescent NPs offer a promising platform for the development of in vivo optical nanoprobes.展开更多
The application of aggregation-induced emission(AIE)materials in biological imaging holds multiple significances,including improving detection sensitivity and specificity,optimizing the imaging process,expanding the s...The application of aggregation-induced emission(AIE)materials in biological imaging holds multiple significances,including improving detection sensitivity and specificity,optimizing the imaging process,expanding the scope of application,and promoting advancements in biomedical research.In this work,the propeller ligand was constructed through McMurry coupling reaction and Suzuki coupling reaction by using dimethoxybenzophenone as the starting material.Then,an imine condensation reaction was carried out in chloroform solution,using a 3:2 molar ratio of precursor to tri(2-aminoethyl)amine to synthesize C3 symmetric porous organic cage CB.The structures of the compounds were determined by nuclear magnetic resonance spectroscopy(NMR),electrospray ionization mass spectrometry(ESI-MS)and Fourier transform infrared spectroscopy(FT-IR).The optical investigation results reveal that ligand L-B and the porous organic cage C_(B) demonstrate remarkable aggregation-induced emission(AIE)properties in a tetrahydrofuran/water mixed solvent system,along with a pronounced response to tetrahydrofuran vapor stimuli.Consequently,Furthermore,given its unique cage-like structure,high quantum yield,and outstanding AIE behavior,the porous organic cage C_(B) holds promise for applications in cell imaging.展开更多
Excited-state intramolecular proton-transfer(ESIPT)based fluorescence probes are particularly attractive due to their unique properties including environmental sensitivity,a large Stokes shift,and potential for ratiom...Excited-state intramolecular proton-transfer(ESIPT)based fluorescence probes are particularly attractive due to their unique properties including environmental sensitivity,a large Stokes shift,and potential for ratiometric sensing.In general,ESIPT-based fluorophore incorporates an intramolecular hydrogen bonding interaction between a hydrogen bond donor(-OH and NH_(2)are common)and a hydrogen bond acceptor(C=N and C=O).More,protection-deprotection of hydroxyl group as hydrogen bond donor could induce an off-on switch of ESIPT-based emission.Therefore,protection-deprotection of hydroxyl group has been the widely used strategy to design fluorescent probes,where the potential key issue is selecting a protective group that can specifically leave in the presence of the target analyte.In this review,we mainly summarize the specific protecting groups(sites)and deprotection mechanisms for biologically important species(including reactive sulfur species(RSS),reactive oxygen species(ROS),enzymes,etc.),and analyze the advantages and disadvantages of different protection mechanisms from some aspects including probe stability,selectivity,response rate and assay system,etc.Based on the aforementioned,we further point out the current challenges and the potential future direction for developing ESIPT-based probes.展开更多
Fluorogenic probes with"off-on"fluorescence signals have emerged as powerful tools for biosensing and bioimaging of biomolecules in living systems.Conventional single-target probes,however,often suffer from ...Fluorogenic probes with"off-on"fluorescence signals have emerged as powerful tools for biosensing and bioimaging of biomolecules in living systems.Conventional single-target probes,however,often suffer from false-positive signals due to non-specific activation in non-target tissues or the diffusion of activated fluorescent products.To address these limitations,dual-targeted fluorogenic probes(DTFPs)have been developed,which simultaneously target two biomarkers to enhance detection specificity and minimize false-positive outcomes.DTFPs are designed to activate or retain fluorescence only when both biomarkers are present within a targeted region,enabling precise in vivo imaging of pathological conditions such as tumors and inflammation.This review highlights recent advances in DTFP development,focusing on their design principles,activation mechanisms,and applications in biosensing and bioimaging.We also discuss current challenges and future directions for DTFP research,aiming to inspire the design of next-generation probes with improved accuracy and specificity.By providing a comprehensive overview of DTFPs,this review seeks to advance their potential for transformative applications in biomedical imaging and diagnostics.展开更多
Singlet oxygen(^(1)O_(2)),as the primary reactive oxygen species in photodynamic therapy,can effectively induce excessive oxidative stress to ablate tumors and kill germs in clinical treatment.However,monitoring endog...Singlet oxygen(^(1)O_(2)),as the primary reactive oxygen species in photodynamic therapy,can effectively induce excessive oxidative stress to ablate tumors and kill germs in clinical treatment.However,monitoring endogenous^(1)O_(2)is greatly challenging due to its extremely short lifetime and high reactivity in biological condition.Herein,we report an ultra-high signal-to-ratio near-infrared chemiluminescent probe(DCMCy)for the precise detection of endogenous^(1)O_(2)during photodynamic therapy(PDT).The methoxy moiety was removed from enolether unit in DCM-Cy to suppress the potential self-photooxidation reaction,thus greatly eliminating the photoinduced background signals during PDT.Additionally,the compact cyclobutane modification of DCM-Cy resulted in a significant 6-fold increase in cell permeability compared to conventional adamantane-dioxane probes.Therefore,our“step-by-step”strategy for DCM-Cy addressed the limitations of traditional chemiluminescent(CL)probes for^(1)O_(2),enabling effectively tracking of endogenous^(1)O_(2)level changes in living cells,pathogenic bacteria and mice in PDT.展开更多
Up to now,numerous emerging methods of cancer treatment including chemodynamic therapy,photothermal therapy,photodynamic therapy,sonodynamic therapy,immunotherapy and chemotherapy have rapidly entered a new stage of d...Up to now,numerous emerging methods of cancer treatment including chemodynamic therapy,photothermal therapy,photodynamic therapy,sonodynamic therapy,immunotherapy and chemotherapy have rapidly entered a new stage of development.However,the single treatment mode is often constrained by the complex tumor microenvironment.Recently,the nanomaterials and nanomedicine have emerged as promising avenues to overcome the limitation in cancer theranostics.Especially,metal-organic frameworks(MOFs)have gained considerable interests in cancer therapy because of their customizable morphologies,easy functionalization,large specific surface area,and good biocompatibility.Among these MOFs,iron-based MOFs(Fe-MOFs)are particularly promising for cancer treatment due to their properties as nano-photosensitizers,peroxidase-like activity,bioimaging contrast capabilities,and biodegradability.Utilizing their structural regularity and synthetic tunability,Fe-MOFs can be engineered to incorporate organic molecules or other inorganic nanoparticles,thereby creating multifunctional nanoplatforms for single or combined theranostic modes.Herein,the minireview focuses on the recent advancements of the Fe-MOFs-based nanoplatforms for self-enhanced imaging and treatment at tumor sites.Furthermore,the clinical research development of Fe-MOFs-based nanoplatforms is discussed,addressing key challenges and innovations for the future.Our review aims to provide novice researchers with a foundational understanding of advanced cancer theranostic modes and promote their clinical applications through the modification of Fe-MOFs.展开更多
Acute lung injury(ALI)is a serious clinical condition with a high mortality rate.Oxidative stress and inflammatory responses play pivotal roles in the pathogenesis of ALI.ONOO^(−)is a key mediator that exacerbates oxi...Acute lung injury(ALI)is a serious clinical condition with a high mortality rate.Oxidative stress and inflammatory responses play pivotal roles in the pathogenesis of ALI.ONOO^(−)is a key mediator that exacerbates oxidative damage and microvascular permeability in ALI.Accurate detection of ONOO^(−)would facilitate early diagnosis and intervention in ALI.Near-infrared fluorescence(NIRF)probes offer new solutions due to their sensitivity,depth of tissue penetration,and imaging capabilities.However,the developed ONOO^(−)fluorescent probes face problems such as interference from other reactive oxygen species and easy intracellular diffusion.To address these issues,we introduced an innovative self-immobilizing NIRF probe,DCI2F-OTf,which was capable of monitoring ONOO^(−)in vitro and in vivo.Importantly,leveraging the high reactivity of the methylene quinone(QM)intermediate,DCI2F-OTf was able to covalently label proteins in the presence of ONOO^(−),enabling in situ imaging.In mice models of ALI,DCI2F-OTf enabled real-time imaging of ONOO^(−)levels and found that ONOO^(−)was tightly correlated with the progression of ALI.Our findings demonstrated that DCI2F-OTf was a promising chemical tool for the detection of ONOO^(−),which could help to gain insight into the pathogenesis of ALI and monitor treatment efficacy.展开更多
Donor-acceptor(D-A)compounds are particularly important in optoelectronic and biological applications.However,they are normally synthesized in the presence of transition metal catalysts.Herein,we report a metal-free m...Donor-acceptor(D-A)compounds are particularly important in optoelectronic and biological applications.However,they are normally synthesized in the presence of transition metal catalysts.Herein,we report a metal-free method by a complexmediated nucleophilic aromatic substitution of aryl nitriles with amines.The method can lead to rich D-A type aggregation-induced emission luminogens(AIEgens)with tunable properties.They emit from deep-blue to yellow-green and possess high photoluminescence quantum yields up to 70.5%in the aggregate state.Interestingly,the suppression of intramolecular flapping is proved to play an indispensable role in the AIE behavior,which is different from the mechanism met in other AIEgens.Moreover,the biocompatible AIEgens possess specific staining of lipid droplets in HeLa cells and the superiority of identifying fatty liver over traditional Oil Red O staining is exhibited.展开更多
The discovery of quantum dots(QDs)stands as one of the paramount technological breakthroughs of the 20th century.Their versatility spans from everyday applications to cutting-edge scientific research,encompassing area...The discovery of quantum dots(QDs)stands as one of the paramount technological breakthroughs of the 20th century.Their versatility spans from everyday applications to cutting-edge scientific research,encompassing areas such as displays,lighting,photocatalysis,bio-imaging,and photonics devices and so on.Among the myriad QDs technologies,industrially relevant CuInS_(2)(CIS)QDs have emerged as promising alternatives to traditional Cd-and Pb-based QDs.Their tunable optoelectronic properties,high absorption coefficient,compositional flexibility,remarkable stability as well as Restriction of Hazardous Substances-compliance,with recent trends revealing a renewed interest in this material for various visible and near-infrared technological applications.This review focuses on recent advancements in CIS QDs as multidisciplinary field from its genesis in the mid-1990 to date with an emphasis on key breakthroughs in their synthesis,surface chemistry,post-synthesis modifications,and various applications.First,the comparation of properties of CIS QDs with relevant knowledge from other classes of QDs and from Ⅰ-Ⅱ-Ⅲ semiconductors as well is summarized.Second,recent advances in the synthesis methods,structure-optoelectronic properties,their defects,and passivation strategies as well as CIS-based heterostructures are discussed.Third,the state-of-the-art applications of CIS QDs ranging from solar cells,luminescence solar concentrations,photocatalysis,light emitting diodes,bioimaging and some emerging applications are summarized.Finally,we discuss open challenges and future perspectives for further advancement in this field.展开更多
Carbon quantum dots(CQDs)have re-ceived increasing interest owing to their excellent optical and chemical characteristics,and high biocompatibil-ity.Herein,turmeric was employed as a carbon source to fabricate green C...Carbon quantum dots(CQDs)have re-ceived increasing interest owing to their excellent optical and chemical characteristics,and high biocompatibil-ity.Herein,turmeric was employed as a carbon source to fabricate green CQDs(named WT-JHCQDs)by hydrother-mal technique.The fluorescence of WT-JHCQDs is particularly stable at differ-ent pH and high concentrations of NaCl.Moreover,WT-JHCQDs exhibit low cytotoxicity,good antioxidant properties,and outstanding biocompatibility.The WT-JHCQDs possess protruding ability of cell imaging and bacteria imaging.This work provides a promising strat-egy for designing excellent fluorescent probes for bioimaging.展开更多
Three-dimensional (3D) visualization of dynamic biological processes in deep tissue remains challenging due to the trade-off between temporal resolution and imaging depth. Here, we present a novel near-infrared-II (NI...Three-dimensional (3D) visualization of dynamic biological processes in deep tissue remains challenging due to the trade-off between temporal resolution and imaging depth. Here, we present a novel near-infrared-II (NIR-II, 900–1880nm) fluorescence volumetric microscopic imaging method that combines an electrically tunable lens (ETL) with deep learning approaches for rapid 3D imaging. The technology achieves volumetric imaging at 4.2 frames per second (fps) across a 200 μm depth range in live mouse brain vasculature. Two specialized neural networks are utilized: a scale-recurrent network (SRN) for image enhancement and a cerebral vessel interpolation (CVI) network that enables 16-fold axial upsampling. The SRN, trained on two-photon fluorescence microscopic data, improves both lateral and axial resolution of NIR-II fluorescence wide-field microscopic images. The CVI network, adapted from video interpolation techniques, generates intermediate frames between acquired axial planes, resulting in smooth and continuous 3D vessel reconstructions. Using this integrated system, we visualize and quantify blood flow dynamics in individual vessels and are capable of measuring blood velocity at different depths. This approach maintains high lateral resolution while achieving rapid volumetric imaging, and is particularly suitable for studying dynamic vascular processes in deep tissue. Our method demonstrates the potential of combining optical engineering with artificial intelligence to advance biological imaging capabilities.展开更多
DNA nanomaterials hold great promise in biomedical fields due to its excellent sequence programmability,molecular recognition ability and biocompatibility.Hybridization chain reaction(HCR)is a simple and efficient iso...DNA nanomaterials hold great promise in biomedical fields due to its excellent sequence programmability,molecular recognition ability and biocompatibility.Hybridization chain reaction(HCR)is a simple and efficient isothermal enzyme-free amplification strategy of DNA,generating nicked double helices with repeated units.Through the design of HCR hairpins,multiple nanomaterials with desired functions are assembled by DNA,exhibiting great potential in biomedical applications.Herein,the recent progress of HCR-based DNA nanomaterials for biosensing,bioimaging and therapeutics are summarized.Representative works are exemplified to demonstrate how HCR-based DNA nanomaterials are designed and constructed.The challenges and prospects of the development of HCR-based DNA nanomaterials are discussed.We envision that rationally designing HCR-based DNA nanomaterials will facilitate the development of biomedical applications.展开更多
Ultrasmall gold nanoparticles(AuNPs)typically includes atomically precise gold nanoclusters(AuNCs)and AuNPs with a core size below 3 nm.Serving as a bridge between small molecules and traditional inorganic nanoparticl...Ultrasmall gold nanoparticles(AuNPs)typically includes atomically precise gold nanoclusters(AuNCs)and AuNPs with a core size below 3 nm.Serving as a bridge between small molecules and traditional inorganic nanoparticles,the ultrasmall AuNPs show the unique advantages of both small molecules(e.g.,rapid distribution,renal clearance,low non-specific organ accumulation)and nanoparticles(e.g.,long blood circulation and enhanced permeability and retention effect).The emergence of ultrasmall AuNPs creates significant opportunities to address many challenges in the health field including disease diagnosis,monitoring and treatment.Since the nano–bio interaction dictates the overall biological applications of the ultrasmall AuNPs,this review elucidates the recent advances in the biological interactions and imaging of ultrasmall AuNPs.We begin with the introduction of the factors that influence the cellular interactions of ultrasmall AuNPs.We then discuss the organ interactions,especially focus on the interactions of the liver and kidneys.We further present the recent advances in the tumor interactions of ultrasmall AuNPs.In addition,the imaging performance of the ultrasmall AuNPs is summarized and discussed.Finally,we summarize this review and provide some perspective on the future research direction of the ultrasmall AuNPs,aiming to accelerate their clinical translation.展开更多
Viruses are ubiquitous in human life. Some viruses can be used as vectors of genetic engineering and specific pesticides. Other viruses trigger a variety of diseases in humans, animals and plants, resulting in high in...Viruses are ubiquitous in human life. Some viruses can be used as vectors of genetic engineering and specific pesticides. Other viruses trigger a variety of diseases in humans, animals and plants, resulting in high infection rates and mortality. Therefore, convenient, accurate and rapid detection of viruses is of great significance for the diagnosis and treatment of subsequent diseases. In contrast to traditional methods of detection, which rely on time-consuming and complex techniques such as polymerase chain reaction (PCR), fluorescent probes and imaging methods generate real-time results, with high specificity, and have been widely used in viral detection. In this review, the application of viral fluorescent probes in analyzing the molecular structure, detection and biological imaging is discussed. In particular, we categorized the probes based on their specificity for human and plant viruses, reviewing the latest findings and analyzing their limitations. The potential of fluorescent molecular probes in the treatment of viral disease and environmental analysis, and their possible combinations with protein and immune technology are discussed.展开更多
With the increasing emergence of bacterial infections,especially multidrug-resistant(MDR)bacteria,poses an urgent threat.This study demonstrated a novel multifunctional nanotheranostics platform developed by the strat...With the increasing emergence of bacterial infections,especially multidrug-resistant(MDR)bacteria,poses an urgent threat.This study demonstrated a novel multifunctional nanotheranostics platform developed by the strategic integration of both in-situ bio-assembly imaging and target bacteria inactivation.Through the introduction of copper ions into bacteria,the Cu^(2+)could spontaneously bio-selfassembled into a multifunctional copper nanoclusters(NCs)which efficiently enhanced epigallocatechin gallate(EGCG)uptake into bacteria.While visualizing the bacteria,the developed theranostic nanoplatform exhibited highly efficient disinfection activities with negligible side effects as reflected by higher cell viability and insignificant hemolytic effects.Furthermore,the exosomal formulation of EGCG integrated with Cu^(2+)showed an increased intracellular antibacterial activity,which could eliminate most of the methicillin-resistant Staphylococcus aureus(MRSA)phagocytosed by macrophages,guide macrophages toward M2-like phenotype polarization and alleviate inflammation,without exhibiting obvious cytotoxicity on host RAW264.7.The regimen could be viewed as an effective strategy for the sterilization of intractable bacterial infections.展开更多
Nasopharyngeal carcinoma(NPC),a malignant tumor originating from the nasopharynx,is one of the common malignant tumors of the head and neck.There are significant geographical differences in the incidence of nasopharyn...Nasopharyngeal carcinoma(NPC),a malignant tumor originating from the nasopharynx,is one of the common malignant tumors of the head and neck.There are significant geographical differences in the incidence of nasopharyngeal carcinoma,with a high incidence in China and Southeast Asian countries.Herein,we designed and synthesized a novel near-infrared fluorescent(NIRF)probe to detect glutathione(GSH)in cellular and tumor environments using semi-naphthofluorescein(SNAFL)as the fluorescent molecular backbone and 2-fluoro-4-nitrobenzenesulfonate as the recognition moiety.Upon reaction with GSH,SNAFL-GSH emitted a fluorescence signal,and its emission wavelength at 650 nm was remarkably enhanced.The results of selectivity experiments indicated that SNAFL-GSH was able to discriminate GSH from Cys,Hcy,and H_(2) S.Moreover,SNAFL-GSH could image both endogenous and exogenous GSH and distinguish normal and cancer cells by fluorescence signal difference.At the cellular level,cisplatin(DDP)-induced ferroptosis and inhibition of proliferation of various NPC cell lines(CNE2,CNE1,5-8F cells)by erastin combined with DDP were visualized with the help of SNAFL-GSH.In a mouse tumor xenograft model,we successfully employed SNAFL-GSH for the evaluation of the efficacy of erastin combined with DDP in the treatment of NPC.More importantly,the probe could image cancerous tissue sections from NPC patients with an imaging depth of approximately 80µm.It was foreseen that SNAFL-GSH offered great potential for application in the diagnosis and evaluation of the therapeutic efficacy of NPC,and these results would also provide new ideas for the clinical treatment of NPC.展开更多
基金supported by the National Natural Science Foundation of China (Nos. 82061148012, 82027806, 91753106)the National Key Research and Development Program of China (No. 2017YFA0205300)+1 种基金the Primary Research & Development Plan of Jiangsu Province (No. BE2019716)the program of China Scholarships Council (No. 202006090323)。
文摘The five-year survival rate for pancreatic cancer is less than 5%. However, the current clinical multimodal therapy combined with first-line chemotherapy drugs only increases the patient’s median survival from 5.0 months to 7.2 months. Consequently, a new strategy of cancer treatments is urgently needed to overcome this high-fatality disease. Through a series of biometric analyses, we found that KRAS is highly expressed in the tumor of pancreatic cancer patients, and this high expression is closely related to the poor prognosis of patients. It shows that inhibiting the expression of KRAS has great potential in gene therapy for pancreatic cancer. Given those above, we have exploited the possibility of targeted delivery of KRAS shRNA with the intelligent and bio-responsive nanomedicine to detect the special oxidative stress microenvironment of cancer cells and realize efficient cancer theranostics. Our observations demonstrate that by designing the smart self-assembled nanocapsules of melanin with fluorescent nanoclusters we can readily achieve the bio-recognition and bioimaging of cancer cells in biological solution or serum.The self-assembled nanocapsules can make a significant bio-response to the oxidative stress microenvironment of cancer cells and generate fluorescent zinc oxide Nanoclusters in situ for targeted cell bioimaging. Moreover, it can also readily facilitate cancer cell suppression through the targeted delivery of KRAS shRNA and low-temperature hyperthermia. This raises the possibility to provide a promising theranostics platform and self-assembled nanomedicine for targeted cancer diagnostics and treatments through special oxidative stress-responsive effects of cancer cells.
文摘Subcellular localization of proteins can provide key hints to infer their functions and structures in cells. With the breakthrough of recent molecule imaging techniques, the usage of 2D bioimages has become increasingly popular in automatically analyzing the protein subcellular location pat- terns. Compared with the widely used protein 1D amino acid sequence data, the images of protein distribution are more intuitive and interpretable, making the images a better choice at many applications for revealing the dynamic char- acteristics of proteins, such as detecting protein translocation and quantification of proteins. In this paper, we systemati- cally reviewed the recent progresses in the field of automated image-based protein subcellular location prediction, and clas- sified them into four categories including growing of bioim- age databases, description of subcellular location distribution patterns, classification methods, and applications of the pre- diction systems. Besides, we also discussed some potential directions in this field.
基金supported by the National Natural Science Foundation of China(Nos.82272067,81974386,M-0696,and 82273486)Natural Science Foundation of Hunan Province(Nos.2022JJ80052,2024JJ6596)the Innovation Fund for Postgraduate Students of Central South University(No.2023ZZTS0841)。
文摘Colorectal cancer(CRC)is one of the most prevalent malignant tumors worldwide,exhibiting high morbidity and mortality.Lack of efficient tools for early diagnosis and surgical resection guidance of CRC have been a serious threat to the long-term survival rate of the CRC patients.Recent studies have shown that relative higher viscosity was presented in tumor cells compared to that in normal cells,leading to viscosity as a potential biomarker for CRC.Herein,we reported the development of a series of novel viscosity-sensitive and mitochondria-specific fluorescent probes(HTB,HTI,and HTP)for CRC detection.Among them,HTB showed high sensitivity,minimal background interference,low cytotoxicity,and significant viscous response capability,making it an ideal tool for distinguishing colorectal tumor cells from normal cells.Importantly,we have successfully utilized HTB to visualize in a CRC-cells-derived xenograft(CDX)model,enriching its medical imaging capacity,which laid a foundation for further clinical translational application.
基金financial support by Talent Introduction Research Initiation Fund of Shanxi Bethune Hospital(2022RC04)Basic Research Program Youth Science Research Project of Shanxi province(202203021212096)+1 种基金Shanxi Province Clinical Theranostics Technology Innovation Center for Immunologic and Rheumatic Diseases(CXZX-202302)Research Project Plan of Shanxi Provincial Administration of Traditional Chinese Medicine(2023ZYYB2021)。
文摘Carbon dots(CDs)are fluorescent carbon-based nanomaterials with sizes smal-ler than 10 nm,that are renowned for their exceptional properties,including superior anti-photobleaching,excellent biocompatibility,and minimal toxicity,which have received sig-nificant interest.Near-infrared(NIR)light has emerged as an ideal light source in the biolo-gical field due to its advantages of minimal scattering and absorption,long wavelength emission,increased tissue penetration,and reduced interference from biological back-grounds.CDs with efficient absorption and/or emission characteristics in the NIR spectrum have shown remarkable promise in the biomedical uses.This study provides a comprehens-ive overview of the preparation methods and wavelength modulation strategies for near-in-frared CDs and reviews research progress in their use in the areas of biosensing,bioimaging,and therapy.It also discusses current challenges and clinical prospects,aimed at deepening our understanding of the subject and promoting further advances in this field.
基金supported by the National Key R&D Program of China (2023YFA0913600)the Postgraduate Research & Practice Innovation Program of Jiangsu Province (KYCX23-1480)H. Liao and Q. Meng contributed equally to this work.
文摘Optical imaging in vivo holds significant implications for disease diagnosis, and nanoprobes with near-infrared (NIR) emission leverage the deep tissue penetration and high spatiotemporal resolution provided by NIR light, demonstrating considerable application potential. This study presents the design and synthesis of three nitrogen-doped boron–dipyrrin (Aza-BODIPY) molecules: Aza–BDP–OCH_(3), Aza–BDP–OH, and Aza–BDP-I. Leveraging the strong electron-accepting properties of the Aza-BODIPY core, we developed a donor–acceptor–donor (D-A-D) structure for Aza–BDP–OCH_(3) through modifications with triphenylamine and methoxy groups, resulting in NIR fluorescence. Aza–BDP–OH was obtained via demethylation using boron tribromide, whereas Aza–BDP-I was synthesized by introducing iodine into Aza–BDP–OCH_(3). These three molecules self-assemble with the amphiphilic polymer PMHC18-mPEG to form nanoparticles (NPs), yielding optical nanoprobes. The resulting NPs exhibit NIR emission, good water solubility, and biocompatibility. At a concentration of 100 μg·mL^(-1), these NPs demonstrate low biological toxicity, highlighting their potential for biological applications. Following tail vein injection, Aza–BDP-I NPs accumulate in tumors and effectively illuminate them via the enhanced permeability and retention (EPR) effect. Furthermore, these organic NPs were metabolized by the liver. Therefore, Aza-BODIPY-based NIR fluorescent NPs offer a promising platform for the development of in vivo optical nanoprobes.
基金funded by the National Natural Science Foundation of China(Nos.22101267 and 82103686)the Natural Science Foundation of Henan Province(202300410477 and 24230042123)the China Postdoctoral Science Foundation(Nos.2021M692905 and 2024T170832).
文摘The application of aggregation-induced emission(AIE)materials in biological imaging holds multiple significances,including improving detection sensitivity and specificity,optimizing the imaging process,expanding the scope of application,and promoting advancements in biomedical research.In this work,the propeller ligand was constructed through McMurry coupling reaction and Suzuki coupling reaction by using dimethoxybenzophenone as the starting material.Then,an imine condensation reaction was carried out in chloroform solution,using a 3:2 molar ratio of precursor to tri(2-aminoethyl)amine to synthesize C3 symmetric porous organic cage CB.The structures of the compounds were determined by nuclear magnetic resonance spectroscopy(NMR),electrospray ionization mass spectrometry(ESI-MS)and Fourier transform infrared spectroscopy(FT-IR).The optical investigation results reveal that ligand L-B and the porous organic cage C_(B) demonstrate remarkable aggregation-induced emission(AIE)properties in a tetrahydrofuran/water mixed solvent system,along with a pronounced response to tetrahydrofuran vapor stimuli.Consequently,Furthermore,given its unique cage-like structure,high quantum yield,and outstanding AIE behavior,the porous organic cage C_(B) holds promise for applications in cell imaging.
基金National Natural Science Foundation of China(Nos.22277104,22325703,22074084)the Natural Science Foundation of Shanxi Province(No.202203021212184)+3 种基金Research Project supported by Shanxi Scholarship Council of China(No.2022-002)the Basic Research Program of Shanxi Province(Free Exploration)(No.202203021221009)2022 Lvliang City science and technology plan project(Nos.2022SHFZ51,2022GXYF15)Scientific Instrument Center of Shanxi University(No.201512)。
文摘Excited-state intramolecular proton-transfer(ESIPT)based fluorescence probes are particularly attractive due to their unique properties including environmental sensitivity,a large Stokes shift,and potential for ratiometric sensing.In general,ESIPT-based fluorophore incorporates an intramolecular hydrogen bonding interaction between a hydrogen bond donor(-OH and NH_(2)are common)and a hydrogen bond acceptor(C=N and C=O).More,protection-deprotection of hydroxyl group as hydrogen bond donor could induce an off-on switch of ESIPT-based emission.Therefore,protection-deprotection of hydroxyl group has been the widely used strategy to design fluorescent probes,where the potential key issue is selecting a protective group that can specifically leave in the presence of the target analyte.In this review,we mainly summarize the specific protecting groups(sites)and deprotection mechanisms for biologically important species(including reactive sulfur species(RSS),reactive oxygen species(ROS),enzymes,etc.),and analyze the advantages and disadvantages of different protection mechanisms from some aspects including probe stability,selectivity,response rate and assay system,etc.Based on the aforementioned,we further point out the current challenges and the potential future direction for developing ESIPT-based probes.
基金the National Natural Science Foundation of China(22137003 and 21922406)Natural Science Foundation of Jiangsu Province(BK20200301 and BK20190055)the Fundamental Research Funds for the Central Universities(020514380251)are acknowledged.
文摘Fluorogenic probes with"off-on"fluorescence signals have emerged as powerful tools for biosensing and bioimaging of biomolecules in living systems.Conventional single-target probes,however,often suffer from false-positive signals due to non-specific activation in non-target tissues or the diffusion of activated fluorescent products.To address these limitations,dual-targeted fluorogenic probes(DTFPs)have been developed,which simultaneously target two biomarkers to enhance detection specificity and minimize false-positive outcomes.DTFPs are designed to activate or retain fluorescence only when both biomarkers are present within a targeted region,enabling precise in vivo imaging of pathological conditions such as tumors and inflammation.This review highlights recent advances in DTFP development,focusing on their design principles,activation mechanisms,and applications in biosensing and bioimaging.We also discuss current challenges and future directions for DTFP research,aiming to inspire the design of next-generation probes with improved accuracy and specificity.By providing a comprehensive overview of DTFPs,this review seeks to advance their potential for transformative applications in biomedical imaging and diagnostics.
基金supported by National Natural Science Foundation of China(Nos.32121005,22225805,22308101,and 32394001)Shanghai Science and Technology Innovation Action Plan(No.23J21901600)+2 种基金Innovation Program of Shanghai Municipal Education Commission,Shanghai Frontier Science Research Base of Optogenetic Techniques for Cell Metabolism(Shanghai Municipal Education Commission,No.2021 Sci&Tech 03-28)the China Postdoctoral Science Foundation(No.2021M701199)Natural Science Foundation of Shanghai(No.23ZR1416600).
文摘Singlet oxygen(^(1)O_(2)),as the primary reactive oxygen species in photodynamic therapy,can effectively induce excessive oxidative stress to ablate tumors and kill germs in clinical treatment.However,monitoring endogenous^(1)O_(2)is greatly challenging due to its extremely short lifetime and high reactivity in biological condition.Herein,we report an ultra-high signal-to-ratio near-infrared chemiluminescent probe(DCMCy)for the precise detection of endogenous^(1)O_(2)during photodynamic therapy(PDT).The methoxy moiety was removed from enolether unit in DCM-Cy to suppress the potential self-photooxidation reaction,thus greatly eliminating the photoinduced background signals during PDT.Additionally,the compact cyclobutane modification of DCM-Cy resulted in a significant 6-fold increase in cell permeability compared to conventional adamantane-dioxane probes.Therefore,our“step-by-step”strategy for DCM-Cy addressed the limitations of traditional chemiluminescent(CL)probes for^(1)O_(2),enabling effectively tracking of endogenous^(1)O_(2)level changes in living cells,pathogenic bacteria and mice in PDT.
基金National Key Research and Development Program of China(No.2022YFD2200602)111 Project(No.B20088)+1 种基金National Natural Science Foundation of China(Nos.52202345 and 31930076)the Heilongjiang Touyan Innovation Team Program(Tree Genetics and Breeding Innovation Team)。
文摘Up to now,numerous emerging methods of cancer treatment including chemodynamic therapy,photothermal therapy,photodynamic therapy,sonodynamic therapy,immunotherapy and chemotherapy have rapidly entered a new stage of development.However,the single treatment mode is often constrained by the complex tumor microenvironment.Recently,the nanomaterials and nanomedicine have emerged as promising avenues to overcome the limitation in cancer theranostics.Especially,metal-organic frameworks(MOFs)have gained considerable interests in cancer therapy because of their customizable morphologies,easy functionalization,large specific surface area,and good biocompatibility.Among these MOFs,iron-based MOFs(Fe-MOFs)are particularly promising for cancer treatment due to their properties as nano-photosensitizers,peroxidase-like activity,bioimaging contrast capabilities,and biodegradability.Utilizing their structural regularity and synthetic tunability,Fe-MOFs can be engineered to incorporate organic molecules or other inorganic nanoparticles,thereby creating multifunctional nanoplatforms for single or combined theranostic modes.Herein,the minireview focuses on the recent advancements of the Fe-MOFs-based nanoplatforms for self-enhanced imaging and treatment at tumor sites.Furthermore,the clinical research development of Fe-MOFs-based nanoplatforms is discussed,addressing key challenges and innovations for the future.Our review aims to provide novice researchers with a foundational understanding of advanced cancer theranostic modes and promote their clinical applications through the modification of Fe-MOFs.
基金supported by the National Natural Science Foundation of China(Nos.22264013,21961010)Hainan Province Science and Technology Special Fund(Nos.ZDYF2021SHFZ219,ZDYF2022SHFZ037)+4 种基金Special Funds of S&T Cooperation and Exchange Projects of Shanxi Province(No.202204041101040)Natural Science Research Talent Project of Hainan Medical University(No.JBGS202101)Postgraduate Innovative Research Project of Hainan(No.Qhys2021-384)Hainan Province Clinical Medical Center(2021)Project for Functional Materials and Molecular Imaging Science Innovation Group of Hainan Medical University.
文摘Acute lung injury(ALI)is a serious clinical condition with a high mortality rate.Oxidative stress and inflammatory responses play pivotal roles in the pathogenesis of ALI.ONOO^(−)is a key mediator that exacerbates oxidative damage and microvascular permeability in ALI.Accurate detection of ONOO^(−)would facilitate early diagnosis and intervention in ALI.Near-infrared fluorescence(NIRF)probes offer new solutions due to their sensitivity,depth of tissue penetration,and imaging capabilities.However,the developed ONOO^(−)fluorescent probes face problems such as interference from other reactive oxygen species and easy intracellular diffusion.To address these issues,we introduced an innovative self-immobilizing NIRF probe,DCI2F-OTf,which was capable of monitoring ONOO^(−)in vitro and in vivo.Importantly,leveraging the high reactivity of the methylene quinone(QM)intermediate,DCI2F-OTf was able to covalently label proteins in the presence of ONOO^(−),enabling in situ imaging.In mice models of ALI,DCI2F-OTf enabled real-time imaging of ONOO^(−)levels and found that ONOO^(−)was tightly correlated with the progression of ALI.Our findings demonstrated that DCI2F-OTf was a promising chemical tool for the detection of ONOO^(−),which could help to gain insight into the pathogenesis of ALI and monitor treatment efficacy.
基金supported by the National Natural Science Foundation of China(22275072 and 62105184)the Natural Science Foundation of Guangdong Province(2020A1515010622)+1 种基金the Project of Science and Technology of Guangzhou(2024A04J3712)the Teli Young Scholar Program of Beijing Institute of Technology.
文摘Donor-acceptor(D-A)compounds are particularly important in optoelectronic and biological applications.However,they are normally synthesized in the presence of transition metal catalysts.Herein,we report a metal-free method by a complexmediated nucleophilic aromatic substitution of aryl nitriles with amines.The method can lead to rich D-A type aggregation-induced emission luminogens(AIEgens)with tunable properties.They emit from deep-blue to yellow-green and possess high photoluminescence quantum yields up to 70.5%in the aggregate state.Interestingly,the suppression of intramolecular flapping is proved to play an indispensable role in the AIE behavior,which is different from the mechanism met in other AIEgens.Moreover,the biocompatible AIEgens possess specific staining of lipid droplets in HeLa cells and the superiority of identifying fatty liver over traditional Oil Red O staining is exhibited.
基金X.H.acknowledges the financial support by Australian Research Council(ARC)Future Fellowship(FT190100756)M.P.S.gratefully acknowledges the support by the ARC under Discovery Early Career Researcher Award(DECRA)(DE210101565)and Discovery Project(DP230101676).
文摘The discovery of quantum dots(QDs)stands as one of the paramount technological breakthroughs of the 20th century.Their versatility spans from everyday applications to cutting-edge scientific research,encompassing areas such as displays,lighting,photocatalysis,bio-imaging,and photonics devices and so on.Among the myriad QDs technologies,industrially relevant CuInS_(2)(CIS)QDs have emerged as promising alternatives to traditional Cd-and Pb-based QDs.Their tunable optoelectronic properties,high absorption coefficient,compositional flexibility,remarkable stability as well as Restriction of Hazardous Substances-compliance,with recent trends revealing a renewed interest in this material for various visible and near-infrared technological applications.This review focuses on recent advancements in CIS QDs as multidisciplinary field from its genesis in the mid-1990 to date with an emphasis on key breakthroughs in their synthesis,surface chemistry,post-synthesis modifications,and various applications.First,the comparation of properties of CIS QDs with relevant knowledge from other classes of QDs and from Ⅰ-Ⅱ-Ⅲ semiconductors as well is summarized.Second,recent advances in the synthesis methods,structure-optoelectronic properties,their defects,and passivation strategies as well as CIS-based heterostructures are discussed.Third,the state-of-the-art applications of CIS QDs ranging from solar cells,luminescence solar concentrations,photocatalysis,light emitting diodes,bioimaging and some emerging applications are summarized.Finally,we discuss open challenges and future perspectives for further advancement in this field.
基金supported by the Central Guidance on Local Science and Technology Development Fund of Guangxi Province(Gui Ke ZY22096010)Guangxi Nat-ural Science Fundation(2023GXNSFAA026181)BAGUI Scholar Program of Guangxi Province of Chi-na,and Middle-aged and Young Teachers’Basic Abili-ty Promotion Project of Guangxi(2022KY0376).
文摘Carbon quantum dots(CQDs)have re-ceived increasing interest owing to their excellent optical and chemical characteristics,and high biocompatibil-ity.Herein,turmeric was employed as a carbon source to fabricate green CQDs(named WT-JHCQDs)by hydrother-mal technique.The fluorescence of WT-JHCQDs is particularly stable at differ-ent pH and high concentrations of NaCl.Moreover,WT-JHCQDs exhibit low cytotoxicity,good antioxidant properties,and outstanding biocompatibility.The WT-JHCQDs possess protruding ability of cell imaging and bacteria imaging.This work provides a promising strat-egy for designing excellent fluorescent probes for bioimaging.
基金supported by the National Key R&D Program of China (No. 2024YFF1206700)the National Natural Science Foundation of China (No. U23A20487)the Hangzhou Chengxi Sci-tech Innovation Corridor Management Committee.
文摘Three-dimensional (3D) visualization of dynamic biological processes in deep tissue remains challenging due to the trade-off between temporal resolution and imaging depth. Here, we present a novel near-infrared-II (NIR-II, 900–1880nm) fluorescence volumetric microscopic imaging method that combines an electrically tunable lens (ETL) with deep learning approaches for rapid 3D imaging. The technology achieves volumetric imaging at 4.2 frames per second (fps) across a 200 μm depth range in live mouse brain vasculature. Two specialized neural networks are utilized: a scale-recurrent network (SRN) for image enhancement and a cerebral vessel interpolation (CVI) network that enables 16-fold axial upsampling. The SRN, trained on two-photon fluorescence microscopic data, improves both lateral and axial resolution of NIR-II fluorescence wide-field microscopic images. The CVI network, adapted from video interpolation techniques, generates intermediate frames between acquired axial planes, resulting in smooth and continuous 3D vessel reconstructions. Using this integrated system, we visualize and quantify blood flow dynamics in individual vessels and are capable of measuring blood velocity at different depths. This approach maintains high lateral resolution while achieving rapid volumetric imaging, and is particularly suitable for studying dynamic vascular processes in deep tissue. Our method demonstrates the potential of combining optical engineering with artificial intelligence to advance biological imaging capabilities.
基金supported in part by National Natural Science Foundation of China(Nos.22225505,22174097).
文摘DNA nanomaterials hold great promise in biomedical fields due to its excellent sequence programmability,molecular recognition ability and biocompatibility.Hybridization chain reaction(HCR)is a simple and efficient isothermal enzyme-free amplification strategy of DNA,generating nicked double helices with repeated units.Through the design of HCR hairpins,multiple nanomaterials with desired functions are assembled by DNA,exhibiting great potential in biomedical applications.Herein,the recent progress of HCR-based DNA nanomaterials for biosensing,bioimaging and therapeutics are summarized.Representative works are exemplified to demonstrate how HCR-based DNA nanomaterials are designed and constructed.The challenges and prospects of the development of HCR-based DNA nanomaterials are discussed.We envision that rationally designing HCR-based DNA nanomaterials will facilitate the development of biomedical applications.
基金the National Natural Science Foundation of China(Grant 22022403 and 22274058)Fundamental Research Funds for the Central Universities.
文摘Ultrasmall gold nanoparticles(AuNPs)typically includes atomically precise gold nanoclusters(AuNCs)and AuNPs with a core size below 3 nm.Serving as a bridge between small molecules and traditional inorganic nanoparticles,the ultrasmall AuNPs show the unique advantages of both small molecules(e.g.,rapid distribution,renal clearance,low non-specific organ accumulation)and nanoparticles(e.g.,long blood circulation and enhanced permeability and retention effect).The emergence of ultrasmall AuNPs creates significant opportunities to address many challenges in the health field including disease diagnosis,monitoring and treatment.Since the nano–bio interaction dictates the overall biological applications of the ultrasmall AuNPs,this review elucidates the recent advances in the biological interactions and imaging of ultrasmall AuNPs.We begin with the introduction of the factors that influence the cellular interactions of ultrasmall AuNPs.We then discuss the organ interactions,especially focus on the interactions of the liver and kidneys.We further present the recent advances in the tumor interactions of ultrasmall AuNPs.In addition,the imaging performance of the ultrasmall AuNPs is summarized and discussed.Finally,we summarize this review and provide some perspective on the future research direction of the ultrasmall AuNPs,aiming to accelerate their clinical translation.
基金National Natural Science Foundation of China(No.22274061)the 111 Project B17019.Supported by the Fundamental Research Funds for the Central Universities(No.CCNU22QN007)Opening fund of Hubei Key Laboratory of Bioinorganic Chemistry&Materia Medica(No.BCMM202101).
文摘Viruses are ubiquitous in human life. Some viruses can be used as vectors of genetic engineering and specific pesticides. Other viruses trigger a variety of diseases in humans, animals and plants, resulting in high infection rates and mortality. Therefore, convenient, accurate and rapid detection of viruses is of great significance for the diagnosis and treatment of subsequent diseases. In contrast to traditional methods of detection, which rely on time-consuming and complex techniques such as polymerase chain reaction (PCR), fluorescent probes and imaging methods generate real-time results, with high specificity, and have been widely used in viral detection. In this review, the application of viral fluorescent probes in analyzing the molecular structure, detection and biological imaging is discussed. In particular, we categorized the probes based on their specificity for human and plant viruses, reviewing the latest findings and analyzing their limitations. The potential of fluorescent molecular probes in the treatment of viral disease and environmental analysis, and their possible combinations with protein and immune technology are discussed.
基金supported by the National Natural Science Foundation of China(Nos.82061148012,82027806,92061121,91753106)the National Key Research and Development Program of China(No.2017YFA0205300)+1 种基金Primary Research&Development Plan of Jiangsu Province(No.BE2019716)the ISF-NSFC Joint Research Program(No.3258/20)to Yossi Weizmann。
文摘With the increasing emergence of bacterial infections,especially multidrug-resistant(MDR)bacteria,poses an urgent threat.This study demonstrated a novel multifunctional nanotheranostics platform developed by the strategic integration of both in-situ bio-assembly imaging and target bacteria inactivation.Through the introduction of copper ions into bacteria,the Cu^(2+)could spontaneously bio-selfassembled into a multifunctional copper nanoclusters(NCs)which efficiently enhanced epigallocatechin gallate(EGCG)uptake into bacteria.While visualizing the bacteria,the developed theranostic nanoplatform exhibited highly efficient disinfection activities with negligible side effects as reflected by higher cell viability and insignificant hemolytic effects.Furthermore,the exosomal formulation of EGCG integrated with Cu^(2+)showed an increased intracellular antibacterial activity,which could eliminate most of the methicillin-resistant Staphylococcus aureus(MRSA)phagocytosed by macrophages,guide macrophages toward M2-like phenotype polarization and alleviate inflammation,without exhibiting obvious cytotoxicity on host RAW264.7.The regimen could be viewed as an effective strategy for the sterilization of intractable bacterial infections.
基金supported by the Hainan Province Science and Technology Special Fund(Nos.ZDYF2021SHFZ219,ZDYF2022SHFZ288)National Natural Science Foundation of China(Nos.21961010,22264013,22204037)+3 种基金Hainan Provincial Natural Science Foundation of China(No.822RC831)Natural Science Research Talent Project of Hainan Medical University(No.JBGS202101)Project for Functional Materials and Molecular Imaging Science Innovation Group of Hainan Medical UniversityHainan Province Clinical Medical Center(2021).
文摘Nasopharyngeal carcinoma(NPC),a malignant tumor originating from the nasopharynx,is one of the common malignant tumors of the head and neck.There are significant geographical differences in the incidence of nasopharyngeal carcinoma,with a high incidence in China and Southeast Asian countries.Herein,we designed and synthesized a novel near-infrared fluorescent(NIRF)probe to detect glutathione(GSH)in cellular and tumor environments using semi-naphthofluorescein(SNAFL)as the fluorescent molecular backbone and 2-fluoro-4-nitrobenzenesulfonate as the recognition moiety.Upon reaction with GSH,SNAFL-GSH emitted a fluorescence signal,and its emission wavelength at 650 nm was remarkably enhanced.The results of selectivity experiments indicated that SNAFL-GSH was able to discriminate GSH from Cys,Hcy,and H_(2) S.Moreover,SNAFL-GSH could image both endogenous and exogenous GSH and distinguish normal and cancer cells by fluorescence signal difference.At the cellular level,cisplatin(DDP)-induced ferroptosis and inhibition of proliferation of various NPC cell lines(CNE2,CNE1,5-8F cells)by erastin combined with DDP were visualized with the help of SNAFL-GSH.In a mouse tumor xenograft model,we successfully employed SNAFL-GSH for the evaluation of the efficacy of erastin combined with DDP in the treatment of NPC.More importantly,the probe could image cancerous tissue sections from NPC patients with an imaging depth of approximately 80µm.It was foreseen that SNAFL-GSH offered great potential for application in the diagnosis and evaluation of the therapeutic efficacy of NPC,and these results would also provide new ideas for the clinical treatment of NPC.
