摘要:In recent years the unique size and structure of fluorescent nanoprobe would give it excellent performances including good photo stability,high fluorescence quantum yield and the adjustable length of the excitation and emission wavelengths,and these advantages attract wide attention of researchers. Fluorescent nanoprobe as an important kind of photo-responsive nanomaterial is considered promising in many fields such as small molecules detection,biomacromolecules detection,cellular imaging and real-time in vivo diagnosis,and is expected to become an ideal substitute for traditional organic fluorescent dyes. The aim of this review is to provide a survey on the research progress of the main materials such as quantum dots,metal nanoclusters and metal organic frameworks,including structure and physicochemical property,especially the synthetic method and the application in chemical sensing and biomedical fields,while finally make summary and prospect.
摘要:Optical imaging has great potential for application in the field of preclinical basic research and clinical diagnostics and therapeutics,due to its advantages of high sensitivity and specificity,non-ionizing radiation,simplicity of equipment,low cost,rich nanoprobe candidates,ability to obtain cellular/molecular level information and real-time acquisition capability. However,due to the nature of high scattering and absorption of photons in biological tissues,optical imaging is usually limited by the shallow tissue penetration depth,which largely limits its usage for in vivo biomedical detection of deep-seated lesions. A lot of efforts have been done by researchers to overcome this issue. This paper summarizes and discusses the progress of various common optical imaging techniques,such as fluorescence imaging,bioluminescence/chemiluminescence imaging,photoacoustic imaging,and Raman imaging,in terms of their research progress in tissue penetration. With the development of science and technology,the tissue detection depths of optical modalities have covered a range from microns to centimeters or even to decimeters,and have shown broad application prospects in the fields of biological detection,imaging,diagnosis,intraoperative navigation,and so on. Finally,the main directions of future research of these optical imaging techniques in tissue penetration are prospected.
摘要:Persistent luminescence is a unique optical phenomenon whereby luminescence remains after the stoppage of excitation. Persistent luminescence shows great promise in anticounterfeiting,information and data storage,photocatalysis,sensing,and bioimaging. Due to the absence of in-situ excitation,persistent luminescence nanoparticles(PLNPs) can efficiently eliminate autofluorescence and light scattering interference and have been widely used in bioimaging. In addition,due to the tunable luminescence properties,PLNPs with features of X-ray excitation,long-lived near-infrared emission or multi-mode imaging could facilitate deep tissue imaging,and provide abundant information on cells and tissues. In this review,the recent advances in the synthesis and bioimaging applications of PLNPs were summarized,with focus on the usage of PLNPs in fingerprint imaging,cell imaging and in vivo imaging. We also discuss the challenges and perspectives of PLNPs in bioimaging.
关键词:persistent luminescence;nanoparticles;fingerprint imaging;cell imaging;in vivo bioimaging
摘要:Among the various of molecular medical instruments,stimuli-responsive optical probes stand out due to their ability to alter their optical properties in response to specific external stimuli. This unique feature enhances the detection selectivity and resolution,making them a crucial component for improving disease diagnosis,treatment,and post-treatment monitoring. Surface-enhanced Raman scattering(SERS) spectroscopy technology,rooted in the principles of surface plasmon resonance,holds the power to amplify Raman signals from molecules adhering to nanoscale SERS substrates. This process not only unveils intricate molecular structural details but also touts technical advantages like heightened precision and simultaneous detection of multiple targets. The wealth of research affirms that the strategic design and construction of stimuli-responsive SERS(SR-SERS) probes significantly elevate detection selectivity and imaging resolution. These probes,operating through minimally invasive and targeted means,furnish real-time invaluable insights. Consequently,they have gained substantial traction within the realm of molecular medicine. This paper presents diverse variations of SR-SERS probes,elaborating on their underlying principles and construction methodologies. It provides a comprehensive overview of their recent advancements in the realm of molecular medicine over the past half-decade,and engages in a discourse about the anticipated trajectory of SR-SERS probes in the sphere of molecular medicine.
关键词:stimuli-response;SERS probes;molecular medicine applications
摘要:The tumor microenvironment(TME) exhibits anomalous characteristics,including a deceased pH level,heightened oxidative stress,hypoxia,elevated glutathione concentration,and excessive expression of certain enzymes. These irregular features play an important role in the occurrence and development of tumors,such as promoting tumor cell growth and angiogenesis,regulating immune evasion and cancer metastasis,and mediating localized drug resistance. Nevertheless,they also present distinctive opportunities for the diagnosis and treatment of cancers. Over the past decade,based on the abnormal characteristics of TME and in combination with the fingerprint spectral traits of surface-enhanced Raman spectroscopy(SERS),a series of SERS probes have been developed to investigate TME and explore related approaches for cancer diagnosis and treatment. These TME-responsive SERS probes offer a range of benefits,including high sensitivity,excellent specificity,the ability of in situ detection,as well as the capability for multivariate analysis. This article provides an overview of the current designs of SERS probes employed for the detection of TME,in accordance with the different characteristics of TME and the varied SERS response mechanisms. In the end,we prospect the potential future development of TME-responsive SERS probes and also discuss the challenges associated with their clinical implementation.
摘要:Cancer has posed serious threats to the health of all human beings due to its high morbidity and mortality. However,traditional cancer treatment methods,such as surgery,radiotherapy and chemotherapy,have encountered the limitations including severe trauma,high recurrence rates and significant toxic side effects. Therefore,it is an urgent need for the development of new cancer treatment method. Among all the new cancer treatments,photodynamic therapy(PDT) has received widespread attention due to its advantages of non-invasiveness,low drug resistance,low toxicity and elimination of the invisible tumor lesions. However,due to the difficulty of light source for penetrating deep tissues,PDT is not effective in the treatment of deep tumors. Sonodynamic therapy(SDT) utilizes ultrasound to activate sonosensitizers to generate reactive oxygen species(ROS) and carbon free radicals,thereby inducing tumor cell death. In addition,SDT not only inherits all the advantages of PDT but also effectively overcomes the problem of insufficient tissue penetration of PDT,which shows a broad clinical application prospect. This review outlines the possible mechanisms of SDT and the types of sonosensitizers,summarizes the challenges faced by development of SDT,and looks forward the possible future development direction.
摘要:Among various biosensing and imaging probes,optical responsive probes are widely used due to their advantages of high specificity and high sensitivity. Energy transfer-based optical biosensing and bioimaging techniques have superior high signal-to-noise ratios,which enable more sensitive,broader,and more precise sensing. This paper introduced the applications of optical biosensing and bioimaging technologies in the field of disease research and therapy based on three energy transfer modes,such as,Förster resonance energy transfer(FRET),nanometal surface energy transfer(NSET) and plasmon resonance energy transfer(PRET). The aim is to provide a reference for the practical application of energy transfer-based optical bioprobes. The prospects and future trends of energy transfer-based optical biosensors and biological imaging technologies are also discussed by exploring the problems of currently developed detection methods.
关键词:energy transfer;FRET;NSET;PRET;bioprobes;bioimaging;molecular medicine
摘要:Cell imaging plays a crucial role in life science and drug discovery research. Raman spectroscopy,a non-destructive vibration spectroscopic technology,enables the imaging of various cellular components when combining with label-free or labeling techniques. Due to the low sensitivity of spontaneous Raman scattering,it is necessary to utilize efficient enhancement methods to increase the space and time resolutions of cellular Raman imaging. In this review,we summarized the advancement of surface-enhanced Raman spectroscopy(SERS),coherent Raman spectroscopy(CRS),resonance Raman spectroscopy(RRS),and other Raman enhancement methods applied for cellular organelle imaging of mitochondria,lysosomes,endoplasmic reticulum,and etc.,as well as for cellular biomolecule imaging of proteins,lipids,sugars,nucleic acids and etc. We discussed the factors of labeling techniques influencing cell imaging results,including the probe structures,enhancement factors,and detection limits,and analyzed the current challenges and future trends of developing Raman spectroscopic technology for cell imaging.
摘要:Neurotransmitters are a class of pivotal chemical substances operating within the neural system,and their abnormal levels are intricately linked to a spectrum of neurological disorders. Among a multitude of techniques employed for neurotransmitter detection,fluorescent probes have emerged as formidable contenders due to their inherent attributes of high selectivity,sensitivity,and visualizability. In this review,we mainly summarized the recent advances in responsive fluorescent probes for neurotransmitter detection since 2019,providing an exposition on six categories of neurotransmitters encompassing acetylcholine,biogenic amines,amino acids,neuropeptides,purines,and gaseous signaling molecules. Furthermore,according to the in-depth analysis of the structural and reaction activity of these neurotransmitters,we expound upon the underlying design principles and reaction mechanisms governing the corresponding probes. These studies provide important methodological and theoretical support for the accurate detection of neurotransmitters and are expected to play a key role in the early diagnosis and treatment of neurological diseases. In addition,the review casts a discerning eye towards prospective trajectories,and emphasizes the continuous improvement of fluorescent probes to meet the needs of neurotransmitter research and clinical needs,so as to provide reference for future research.
摘要:Membrane proteins are an important component of cell membranes and play a vital role in basic physiological activities such as signal transduction,mass transport and energy exchange. Abnormalities in membrane protein expression,structure and function are closely associated with various diseases such as malignant tumors. Membrane proteins have attracted enormous attention in chemistry,biology,medicine and other fields. Developing methods in situ for analysis of the expression,spatial distribution and organization of membrane proteins is essential for understanding the molecular basis of membrane protein functions and cellular physiological activities. Researchers have recently developed a series of membrane protein in situ imaging technology,includingfluorescence imaging,electrochemiluminescence imaging,surface-enhanced Raman scattering,etc. These imaging technologies have played an important role in studying the structure and function of membrane proteins. This article reviews the recent progress in the field of membrane protein in situ imaging and summarizes representative membrane protein in situ imaging technology. The challenges and future perspectives in membrane protein in situ imaging are also briefly discussed.
摘要:Visualization of biological behavior is essential to basic and clinical medical research. Surface-enhanced Raman spectroscopy(SERS) as a rising powerful optical technology attracted a lot of interest due to noninvasive,highly sensitive,rapid and multiplex characteristics. Despite in vitro molecular sensing is highly sensitive,it is not possible to real-time visualize the spatiotemporal dynamics of small molecule functions in vivo. The existing SERS imaging speed and accuracy isn’t enough for the demand of in vivo imaging. This review focuses on the update breakthrough of the development of SERS imaging through more sensitive,controllable and accurate nanoprobes,such as gap-enhanced core-shell nanoparticles,semiconductor composite nanoparticles,Raman silent-region probes. SERS imaging is increasingly being studied for bacteria,tumor surveillance and photothermal therapy. When preparing SERS probes,it is necessary to consider the clearance of background signals,the penetration depth of in vivo detection,the targeting of targets,the non-destructive nature of normal tissues,and the in vivo clearance of probes. Further,we illustrate the application of SERS in vivo imaging ranging from cell imaging to tissue imaging. Finally,we provide prospects on the possible obstacles of SERS bioimaging in future development. Encouraging application results show that SERS imaging has great potential for clinical disease prevention,diagnosis and treatment.
摘要:Surface-enhanced Raman scattering(SERS) technology,as a highly sensitive and high-resolution analytical method,has shown broad application prospects in the field of bacterial research. Not only bacterial content can be detected at extremely low concentration levels,but its microscopic resolution can penetrate deep into the interior of bacteria,providing an opportunity for a profound understanding of bacterial composition and metabolic behavior. Without the need for complex pre-treatment steps,SERS technology can simultaneously monitor multiple bacterial metabolites,improving the efficiency and accuracy of analysis. These characteristics make SERS technology a powerful tool for comprehensively understanding the physiological activity and metabolites of bacteria. This article first introduces the concept,enhancement mechanism,and enhancement substrate materials of SERS technology,and then focuses on the research progress of SERS technology in the analysis of bacterial physiological active factors and metabolites. Finally,while pointing out its limitations,it also looks forward to future development trends.
摘要:Carbon dots have shown enormous application potential in the fields of biomedicine,and energy catalysis due to their excellent optical properties and good biocompatibility. Environmentally sensitive carbon dots are a unique carbon-based material that can respond to surrounding environments,creating changes. These novel materials received great attention in sensing fields. This review summarized the recent progress in the environmentally responsive mechanisms of carbon dots from four environmental factors,including pH,polarity,viscosity,and temperature. We retrospected their biosensing applications,with the expectation of developing more new environmentally sensitive carbon dots for broader application fields.
摘要:Post-translational modifications of proteins play a crucial regulatory role within cells,exerting significant impacts on cellular functions and metabolism. In recent years,the application of fluorescent probes in the study of protein post-translational modifications has been continuously evolving. This review will primarily focus on the applications of fluorescent probes in modifications such as protein phosphorylation and glycosylation,encompassing their principles,design strategies,as well as their utilization within cells and organisms. The development of small molecule fluorescent probes provides a robust tool for investigating protein post-translational modifications,holding the potential to deepen our understanding of these processes and offering novel avenues for drug development and disease diagnosis.
摘要:Photoacoustic(PA) imaging,a promising imaging technology that integrates characteristics of optical imaging with acoustic imaging,enables non-invasive imaging modality with high spatiotemporal resolution and deep tissue penetration. Thus,PA imaging has shown great potential in biomedical and clinical applications. In recent years,to dynamically visualize the specific biological process in vivo,a series of stimuli-responsive photoacoustic nanoagents are develpoed with better real-time diagnostic capability. Those PA imaging agents possess activable PA intensities in responding to specific stimuli. From this perspective,this review will summarize the general strategies and recent advances for developing stimuli-responsive PA nanoagents,including internal stimuli,such as pH,enzyme,free radical,ect,as well as external stimuli,such as light,thermal,ultrasound,ect. Furthermore,current challenges and outlooks for developing activable PA nanoagents will be discussed.
摘要:Organelles,which are important devices for maintaining normal cellular activity,are specific organelle microenvironments surrounded by lipid bilayers. Different organelles need to perform their specific cellular functions under different microenvironmental conditions,and the disruption of microenvironmental homeostasis would lead to disease. Among them,mitochondria,as the energy factories of cells,plays an important role in regulating cellular redox levels and free radical homeostasis. Therefore,the monitoring of reactive oxygen species(ROS) in mitochondrial microenvironment can deepen the understanding of the physiopathology associated with it. It has been reported that chemical small molecule fluorescent probes have unique advantages in detecting the cellular microenvironment,and the understanding of mitochondria-associated diseases. Therefore,this paper mainly focus on fluorescent probes targeting ROS such as superoxide anion(O2·-),hypochlorous acid(HClO),hydrogen peroxide(H2O2),and nitric oxide(NO) and peroxynitrite(ONOO-) in mitochondria.
摘要:Hexavalent chromium[Cr(Ⅵ)] is toxic and carcinogenic,posing a significant threat to human health. Therefore,the development of rapid,sensitive and accurate methods for detecting Cr(Ⅵ) is of great importance. Herein,manganese,chlorine and nitrogen co-doped carbon dots(Mn,Cl,N-CDs) were synthesized by a one-step hydrothermal method using o-phenylenediamine,p-aminobenzoic acid,manganese chloride and concentrated hydrochloric acid as reaction precursors. Mn,Cl,N-CDs can emit bright and stable red fluorescence with a fluorescence quantum yield of 5.3%. Based on the aggregation-induced and dynamic quenching effects,the addition of Cr(Ⅵ) leads to a significant change in the fluorescence intensity and absorbance of Mn,Cl,N-CDs. Consequently,a dual-mode sensor for fluorescence and colorimetry,along with a smartphone imaging method,was developed to achieve sensitive detection of Cr(Ⅵ). The linear ranges of Cr(Ⅵ) were 33.8-469.5 μmol/L and 2.4-80.7 μmol/L for fluorescence and colorimetric methods,respectively,and 20.0-160.0 μmol/L(visible light irradiation) and 80.0-170.0 μmol/L(UV irradiation) for smartphone imaging. This paper not only successfully constructed a sensor for the quantitative detection of Cr(Ⅵ) using smartphone imaging,but also introduced an innovative approach for creating intelligent,portable and visual sensors based on CDs.
关键词:manganese,chlorine and nitrogen co-doped carbon dots;optical dual-mode;smartphone imaging;Cr(Ⅵ)
摘要:As a type of functional nucleic acid with enzymatic activity,DNAzymes are widely used in analytical fields such as biosensing due to their structural advantages that are different from proteases and ribozymes. However,the structure of DNAzyme is susceptible to degradation by biological enzymes,which slows down the speed of such biosensor development. Although chemical modification can be used to resolve the problem,this strategy has disadvantages,such as being costly and hard to synthesize. Considering this,we choose a new strategy from the sights of structure transformation to resolve this problem. Then,we design and synthesize a kind of circular DNAzyme by utilizing the enzyme-resistance properties of circular nucleic acid structure. The research results show that the circular DNAzyme has better structural stability than traditional single-stranded DNAzymes in exonuclease,tap water,and 75% fetal bovine serum(FBS),and the duration is up to 6 h in 75% FBS. In addition,introducing a circular structure will also enhance the interaction between DNAzymes and substrate sequences,thereby affecting the signal expression of biosensors based on circular DNAzymes. This feature will provide new ideas for constructing DNAzyme-based biosensors.
摘要:In this paper,porous magnetic gold nano-foam nickel composite is in situ prepared as surface enhanced Raman scattering(SERS) substrate(Au-NFs) by directly reducing chloric acid gold solution with treated foam nickel as a reductive reaction template. The three-dimensional network of foam nickel with a large specific surface area and roughness could tightly load gold nanoparticles and chemically adsorb more target molecules 6-mercaptopurine via the Au—S bond. The magnetic properties of the composite substrate make it easy for magnetic separation and enrichment to avoid the interference of blood coexistence species on SERS detection of 6-mercaptopurine. By using magnetic field,porous magnetic Au-NFs can be further optimized the distribution of the local plasma field of gold nanoparticles to form SERS hot spots,which greatly improve the detection sensitivity. For probe molecule 4-mercaptopyridine,the Au-NFs-based SERS detection limit at 5×10-9 mol/L could be reached. Under external magnetic field,with Au-NFs composite substrate,a linear detection of 6-mercaptopurine concentration locates in the range of 5×10-7 and 1×10-8 mol/L,with a detection limit of 1×10-9 mol/L. Without sample pretreatment,this Au-NFs substrate could be used for rapid analysis of 6-mercaptopurine spiked in serum with recoveries ranging from 92.8% to 107%,indicating the reliability of the method.
关键词:nickel foam;Au nanoparticles;magnetic composites;6-mercaptopurine;SERS detection;serum;immunosuppressive drug
摘要:This study describes a non-invasive,real-time analysis of pH levels in human sweat using surface-enhanced Raman scattering(SERS) technology. The researchers addressed issues such as poor stability caused by signal fluctuations by developing a novel sensor called the petal-like gap-enhanced Raman tag(PGERT). The sensor utilizes 4-mercaptobenzonitrile(4-MBN) molecules internally for an internal standard Raman signal and externally modifies the surface with 4-mercaptobenzoic acid(4-MBA) pH-sensing molecules to enhance the probe signal. Through in situ analysis,the study established standard analysis curves under pH conditions ranging from 5.0 to 8.0,achieving a high correlation coefficient(r2) of up to 0.99. The sensor demonstrated high stability and sensitivity. Error rates between the sensor's detection results for sweat at different pH levels(pH 5.0 to 7.0) and standard pH meter measurements were(2.17±5.0)%,(4.62±1.1)%,(5.80±0.3)% and (3.68±1.0)%,respectively. These results indicate that the sensor,based on the internal standard PGERT,can be applied for monitoring pH levels in human sweat,offering advantages such as high sensitivity,stability,and precise analysis.