Evaluation of COC183B2 antibody targeting ovarian cancer by near-infrared fluorescence imaging

Objective: To evaluate the imaging potential of a novel near-infrared(NIR) probe conjugated to COC183 B2 monoclonal antibodies(MAb) in ovarian cancer(OC).Methods: The expression of OC183 B2 antigen in OC was determined by immunohistochemical(IHC) staining using tissue microarrays with the H-score system and immunofluorescence(IF) staining of tumor cell lines.Imaging probes with the NIR fluorescent dye cyanine 7(Cy7) conjugated to COC183 B2 Mab were chemically engineered. OC183 B2-positive human OC cells(SKOV3-Luc) were injected subcutaneously into BALB/c nude mice. Bioluminescent imaging(BLI) was performed to detect tumor location and growth. COC183 B2-Cy7 at 1.1,3.3, 10, or 30 μg were used for in vivo fluorescence imaging, and phosphate-buffered saline(PBS), free Cy7 dye and mouse isotype immunoglobulin G(IgG)-Cy7(delivered at the same doses as COC183 B2-Cy7) were used as controls.Results: The expression of OC183 B2 with a high H-score was more prevalent in OC tissue than fallopian tube(FT) tissue. Among 417 OC patients, the expression of OC183 B2 was significantly correlated with the histological subtype, histological grade, residual tumor size, relapse state and survival status. IF staining demonstrated that COC183 B2 specifically expressed in SKOV3 cells but not HeLa cells. In vivo NIR fluorescence imaging indicated that COC183 B2-Cy7 was mainly distributed in the xenograft and liver with optimal tumor-to-background(T/B)ratios in the xenograft at 30 μg dose. The highest fluorescent signals in the tumor were observed at 96 h postinjection(hpi). Ex vivo fluorescence imaging revealed the fluorescent signals mainly from the tumor and liver. IHC analysis confirmed that xenografts were OC183 B2 positive.Conclusions: COC183 B2 is a good candidate for NIR fluorescence imaging and imaging-guided surgery in OC.

Near-infrared fluorescence imaging of a solitary fibrous tumor of the pancreas using methylene blue

A 67-year-old female presented with unexplained abdominal pain. A contrast-enhanced computed tomography scan of the abdomen incidentally revealed a mass in the uncinate process of the pancreas. This mass was resected and based on histopathological findings, diagnosed as a solitary fibrous tumor (SFT) of the pancreas. A SFT is an extremely rare benign mesenchymal tumor that in 65% of cases affects the visceral pleura but can also affect extra-pleural sites. The intraoperative demarcation of pancreatic tumors, such as SFTs, can bechallenging. In this report, the first clear intraoperative identification of a SFT of the pancreas in a human was shown using near-infrared fluorescence and methylene blue.

A"donor–acceptor"structured semiconductor polymer for near infrared fluorescence imaging guided photodynamic therapy

Near infrared(NIR)fluorescence imaging guided photodynamic therapy(PDT)is a technique which has been developed in many clinical trials due to its advantage of real-time optical monitoring,specific spatiotemporal selectivity,and minimal invasiveness.For this,photosensitizers with NIR fluorescence emission and high^(1)O_(2)generation quantum yield are highly desirable.Herein,we designed and synthesized a"donor-acceptor"(D-A)structured semiconductor polymer(SP),which was then wrapped with an amphiphilic compound(Pluronic■F127)to prepare water-soluble nanoparticles(F-SP NPs).The obtained F-SP NPs exhibit good water solubility,excellent particle size stability,strong absorbance at deep red region,and strong NIR fluorescent emission characteristics.The maximal mass extinction coe±cient and fluorescence quantum yield of these F-SPs were calculated to be 21.7 L/(g·cm)and 6.5%,respectively.Moreover,the^(1)O_(2)quantum yield of 89%for F-SP NPs has been achieved under 635 nm laser irradiation,which is higher than Methylene Blue,Ce6,and PpIX.The outstanding properties of these F-SP NPs originate from their unique D-A molecular characteristic.This work should help guide the design of novel semiconductor polymer for NIR fluorescent imaging guided PDT applications.

Novel imaging system for positioning of the indocyanine green (ICG) target;visible projection of the near-infrared fluorescence image

Background: Even though NIR fluorescence imaging has many advantages in SLN mapping and cancer detection, NIR fluorescence imaging shows a serious drawback that NIR cannot be detected by the naked eye without any detectors. This limitation further disturbs accurate SLN detection and adequate tumor resection resulting in the presence of cancerous cells near the boundaries of surgically removed tissues. Materials and methods: To overcome the drawback of the conventional NIR imaging method, we suggest a novel NIR imaging system which can make the NIR fluorescence image visible to the naked eye as NIR fluorescence image detected by a video camera is processed by a computer and then projected back onto the NIR fluorescence excitation position with a projector using conspicuous color light. Image processing techniques were used for projection onto the exact position of the NIR fluorescence image. Also, we implemented a phantom experiment to evaluate the performance of the developed NIR fluorescence projection system by use of the ICG. Results: The developed NIR fluorescence projection system was applied in normal mouse model to confirm the usefulness of the system in the clinical field. A BALB/c nude mouse was prepared to be applied in normal mouse model and 0.25 mg/ml stock solution of the ICG was injected through a tail vein of the mouse. From the application in normal mouse model, we could confirm that the injected ICG stayed in the liver of the mouse and verify that the projection system projected the ICG fluorescence image at the exact location of the ICG by performing laparotomy of the mouse. Conclusions: From the application in normal mouse model, we could verify that the ICG fluorescence image was precisely projected back on the site where ICG fluorescence generated. It can be demonstrated that the NIR fluorescence projection system can make it possible to visualize the invisible NIR fluorescence image and to realize that SLN mapping and cancer detection in clinical surgery.

An acidic medium-compatible deep-near-infrared dye for in vivo imaging

In vivo imaging in the deep near-infrared(NIR)spectral region,that is,beyond 800 nm,has become popular due to its penetration depth.While imaging of the neutral medium/tissue has been repeatedly showcased,imaging of the high-acidic medium remains challenging partly because of the high-lying HOMO orbital and hence a high pKa of the electron-donating group of the NIR fluorophores.We devised a novel electron-donating group(D6)with which we further synthesized ECJ.ECJ exhibits an absorption wavelength beyond 900 nm and is fluorescent.Its pKa was found to be lower than zero,rendering it suitable for bioimaging of a highly-acidic medium.Its potential for practical applications was showcased in proof-of-concept in vivo imaging with a mouse model.

Application value of indocyanine green fluorescence imaging in guiding sentinel lymph node biopsy diagnosis of gastric cancer: Meta-analysis

BACKGROUND Gastric cancer is a common malignant tumor of the digestive system worldwide,and its early diagnosis is crucial to improve the survival rate of patients.Indocyanine green fluorescence imaging(ICG-FI),as a new imaging technology,has shown potential application prospects in oncology surgery.The meta-analysis to study the application value of ICG-FI in the diagnosis of gastric cancer sentinel lymph node biopsy is helpful to comprehensively evaluate the clinical effect of this technology and provide more reliable guidance for clinical practice.AIM To assess the diagnostic efficacy of optical imaging in conjunction with indocya-nine green(ICG)-guided sentinel lymph node(SLN)biopsy for gastric cancer.METHODS Electronic databases such as PubMed,Embase,Medline,Web of Science,and the Cochrane Library were searched for prospective diagnostic tests of optical imaging combined with ICG-guided SLN biopsy.Stata 12.0 software was used for analysis by combining the"bivariable mixed effect model"with the"midas"command.The true positive value,false positive value,false negative value,true negative value,and other information from the included literature were extracted.A literature quality assessment map was drawn to describe the overall quality of the included literature.A forest plot was used for heterogeneity analysis,and P<0.01 was considered to indicate statistical significance.A funnel plot was used to assess publication bias,and P<0.1 was considered to indicate statistical significance.The summary receiver operating characteristic(SROC)curve was used to calculate the area under the curve(AUC)to determine the diagnostic accuracy.If there was interstudy heterogeneity(I2>50%),meta-regression analysis and subgroup analysis were performed.analysis were performed.RESULTS Optical imaging involves two methods:Near-infrared(NIR)imaging and fluorescence imaging.A combination of optical imaging and ICG-guided SLN biopsy was useful for diagnosis.The positive likelihood ratio was 30.39(95%CI:0.92-1.00),the sensitivity was 0.95(95%CI:0.82-0.99),and the specificity was 1.00(95%CI:0.92-1.00).The negative likelihood ratio was 0.05(95%CI:0.01-0.20),the diagnostic odds ratio was 225.54(95%CI:88.81-572.77),and the SROC AUC was 1.00(95%CI:The crucial values were sensitivity=0.95(95%CI:0.82-0.99)and specificity=1.00(95%CI:0.92-1.00).The Deeks method revealed that the"diagnostic odds ratio"funnel plot of SLN biopsy for gastric cancer was significantly asymmetrical(P=0.01),suggesting significant publication bias.Further meta-subgroup analysis revealed that,compared with fluorescence imaging,NIR imaging had greater sensitivity(0.98 vs 0.73).Compared with optical imaging immediately after ICG injection,optical imaging after 20 minutes obtained greater sensitivity(0.98 vs 0.70).Compared with that of patients with an average SLN detection number<4,the sensitivity of patients with a SLN detection number≥4 was greater(0.96 vs 0.68).Compared with hematoxylin-eosin(HE)staining,immunohistochemical(+HE)staining showed greater sensitivity(0.99 vs 0.84).Compared with subserous injection of ICG,submucosal injection achieved greater sensitivity(0.98 vs 0.40).Compared with 5 g/L ICG,0.5 and 0.05 g/L ICG had greater sensitivity(0.98 vs 0.83),and cT1 stage had greater sensitivity(0.96 vs 0.72)than cT2 to cT3 clinical stage.Compared with that of patients≤26,the sensitivity of patients>26 was greater(0.96 vs 0.65).Compared with the literature published before 2010,the sensitivity of the literature published after 2010 was greater(0.97 vs 0.81),and the differences were statistically significant(all P<0.05).CONCLUSION For the diagnosis of stomach cancer,optical imaging in conjunction with ICG-guided SLN biopsy is a therapeut-ically viable approach,especially for early gastric cancer.The concentration of ICG used in the SLN biopsy of gastric cancer may be too high.Moreover,NIR imaging is better than fluorescence imaging and may obtain higher sensitivity.

Mechanism of Dynamic Near-infrared Fluorescence Cholangiography of Extrahepatic Bile Ducts and Applications in Detecting Bile Duct Injuries Using Indocyanine Green in Animal Models

Fluorescence intraoperative cholangiography（IOC） is a potential alternative for identifying anatomical variation and preventing iatrogenic bile duct injuries by using the near-infrared probe indocyanine green（ICG）. However, the dynamic process and mechanism of fluorescence IOC have not been elucidated in previous publications. Herein, the optical properties of the complex of ICG and bile, dynamic fluorescence cholangiography and iatrogenic bile duct injuries were investigated. The emission spectrum of ICG in bile peaked at 844 nm and ICG had higher tissue penetration. Extrahepatic bile ducts could fluoresce 2 min after intravenous injection, and the fluorescence intensity reached a peak at 8 min. In addition, biliary dynamics were observed owing to ICG excretion from the bile ducts into the duodenum. Quantitative analysis indicated that ICG-guided fluorescence IOC possessed a high signal to noise ratio compared to the surrounding peripheral tissue and the portal vein. Fluorescence IOC was based on rapid uptake of circulating ICG in plasma by hepatic cells, excretion of ICG into the bile and then its interaction with protein molecules in the bile. Moreover, fluorescence IOC was sensitive to detect bile duct ligation and acute bile duct perforation using ICG in rat models. All of the results indicated that fluorescence IOC using ICG is a valid alternative for the cholangiography of extrahepatic bile ducts and has potential for measurement of biliary dynamics.

Minimally Invaded Sentinel Lymph Node Model for the Development of Intraoperative Infrared Fluorescence Imaging

In this study we implemented an axillary SLN invasion model to develop highly sensitive imaging strategies enabling detection of a very small amount of tumor cells. A highly diffusible molecular probe targeting &alpha;v&beta;3 and &alpha;v&beta;5 integrins was investigated either via IV or locoregional injections. We additionally documented the potential interferences of this Near Infrared Fluorescence Probe with Blue Patente V and ICG dyes routinely used to facilitate lymph node detection during surgery. The human mammary adenocarcinoma MDA-MB-231-luc model was injected into the forepaw of nude female rats to obtain a controlled invasion of the axillary LN. Thanks to its high sensitivity, BLI was selected to achieve in vivo quantitation of tumor cells in SLNs and determine eligible animals for the study. NIRF of integrins was performed at 680 nm both in vivo and ex vivo using spectral unmixing to suppress auto-fluorescence signal and preserve sensitivity. In vivo BLI was quite reliable in estimating discrete invasion by cancer cells in the LN with thresholds of detection and quantitation of about 500 and 1500 cells respectively. For fluorescence at 680 nm, in vivo imaging is not suitable to detect micro-invasion, but ex vivo fluorescence with spectral unmixing of SLNs confirmed the presence of a tumor burden as low as 1500 cells expressing &alpha;v&beta;3/&alpha;v&beta;5 integrins. Targeting few tumor cells inside a micro-invaded sentinel lymph node by molecular probes is not sensitive enough to provide direct in vivo or peroperative imaging. At the time NIRF is performed on the excised specimen, high sensitivity imaging associated with spectral unmixing allowed such detection within less than 1 minute of examination.

In vivo subsurface morphological and functional cellular and subcellular imaging of the gastrointestinal tract with confocal mini-microscopy

AIM： To evaluate a newly developed hand-held confocal probe for in vivo microscopic imaging of the complete gastrointestinal tract in rodents. METHODS： A novel rigid confocal probe （diameter 7 mm） was designed with optical features similar to the flexible endomicroscopy system for use in humans using a 488 nm single line laser for fluorophore excitation, Light emission was detected at 505 to 750 nm. The field of view was 475 μm × 475 μm. Optical slice thickness was 7 μm with a lateral resolution of 0.7 μm. Subsurface serial images at different depths （surface to 250 μm） were generated in real time at 1024 × 1024 pixels （0.8 frames/s） by placing the probe onto the tissue in gentle, stable contact. Tissue specimens were sampled for histopathological correlation.RESULTS： The esophagus, stomach, small and large intestine and meso, liver, pancreas and gall bladder were visualised in vivo at high resolution in n = 48 mice. Real time microscopic imaging with the confocal minimicroscopy probe was easy to achieve. The different staining protocols （fluorescein, acriflavine, FITC-labelled dextran and L. esculentum lectin） each highlighted specific aspects of the tissue, and in vivo imaging correlated excellently with conventional histology. In vivo blood flow monitoring added a functional quality to morphologic imaging.CONCLUSION： Confocal microscopy is feasible in vivo allowing the visualisation of the complete GI tract at high resolution even of subsurface tissue structures. The new confocal probe design evaluated in this study is compatible with laparoscopy and significantly expands the field of possible applications to intra-abdominal organs. It allows immediate testing of new in vivo staining and application options and therefore permits rapid transfer from animal studies to clinical use in patients.

Intraoperative use of indocyanine green fluorescence imaging in rectal cancer surgery: The state of the art

Indocyanine green(ICG)fluorescence imaging is widely used in abdominal surgery.The implementation of minimally invasive rectal surgery using new methods like robotics or a transanal approach required improvement of optical systems.In that setting,ICG fluorescence optimizes intraoperative vision of anatomical structures by improving blood and lymphatic flow.The purpose of this review was to summarize all potential applications of this upcoming technology in rectal cancer surgery.Each type of use has been separately addressed and the evidence was investigated.During rectal resection,ICG fluorescence angiography is mainly used to evaluate the perfusion of the colonic stump in order to reduce the risk of anastomotic leaks.In addition,ICG fluorescence imaging allows easy visualization of organs such as the ureter or urethra to protect them from injury.This intraoperative technology is a valuable tool for conducting lymph node dissection along the iliac lymphatic chain or to better identifying the rectal dissection planes when a transanal approach is performed.This is an overview of the applications of ICG fluorescence imaging in current surgical practice and a synthesis of the results obtained from the literature.Although further studies are need to investigate the real clinical benefits,these findings may enhance use of ICG fluorescence in current clinical practice and stimulate future research on new applications.

Aggregation-induced emission luminogen for in vivo three-photon fuorescence lifetime microscopic imaging

Compared with visible light,near infrared(NIR)light has deeper penetration in biological tisues.Three-photon fuorescence microscopy(3PFM)can effectively utilize the NIR excitation to obtain high-contrast images in the deep tisue.However,the weak three photon fluorescence signals may be not well presented in the traditional fuorescence intensity imaging mode.Fluorescence lifetime of certain probes is insensitive to the intensity of the excitation laser.Moreover,fluorescence lifetimne imaging microscopy(FLIM)can detect weak signals by utilizing time correlated single photon counting(TCSPC)technique.Thus,it would be an improved strategy to combine the 3PFM imaging with the FLIM together.Herein,DCDPP-2TPA,a novel agegation-induced emission luminogen(AIEgen),was adopted as the fluorescent probes.The three-photon absorption cros-section of the AlEgen,which has a deep-red fluorescence emission,was proved to be large.DCDPP-2TPA nanoparticles were synthesized,and the three photon fluorescence lifetime of which was measured in water.Moreover,in vrivo thre-photon fuorescence lifetime microscopic imaging of a craniotomy mouse was conducted via a home made optical system.High contrast cerebrovascular images of different vertical depths were obtained and the maximun depth was about 600 pumn.Even reaching the depth of 600 pum,tiny capillary vessels as small as 1.9 pum could still be distinguished.The three photon fuorescence lifetimes of the capillaries in some representative images were in accord with that of DCDPP-2TPA nanoparticles in water.A vivid 3D reconstruction was further organized to present a wealth of lifetime information.In the future,the combination strategy of 3PFM and FLIM could be further applied in the brain functional imaging.

A ggregation-induced emission nanoparticles for in vivo three-photon fuorescence microscopic rat brain angiography

Rodents are popular biological models for physiological and behavioral research in neuroscience and rats are better models than mice due to their higher genome similarity to human and more accessible surgical procedures.However,rat brain is larger than mice brain and it needs powerful imaging tools to implement better penetration against the scattering of the thicker brain tissue.Three-photon fluorescence microscopy(3PFM)combined with near-infrared(NIR)excitation has great potentials for brain circuits imaging beause of its abilities of anti scattering,deep-tissue imaging,and high signal-to-noise ratio(SNR).In this work,a type of AIE lumninogen with red fuorescence was synthesized and encapsulated with Pluronic F-127 to make up form nano-particles(NPs).Bright DCDPP-2TPA NPs were employed for in trino three-photon fuorescent laser scanning microscopy of blood vessels in rats brain under 1550 nm femtosecond laser exci-tation.A fine three-dimensional(3D)reconstruction up to the deepness of 600 pm was achieved and the blood flow velocity of a selected vessel was measured in vrito as well.Our 3PFM deep brain imaging method simultaneously recorded the morphology and function of the brain blood vessels in vivo in the rat model.Using this angiography combined with the arsenal of rodent's brain disease,models can accelerate the neuroscience research and clinical diagnosis of brain disease in the future.

MULTISPECTRAL UNMIXING OF FLUORESCENCE MOLECULAR TOMOGRAPHY DATA

Even though multispectral imaging is considered very significant in biological imaging,it is only commonly used in microscopy in a 2D approach.Here,we present a Fluorescence Molecular Tomography system capable of recording simultaneously tomographic data at several spectral windows,enabling multispectral tomography.3D reconstructed data from several spectral windows is used to construct a linear unmixing algorithm for multispectral deconvolution of overlapping fluorescence signals.The method is applied on tomographic 3D fluorescence concentration maps in tissue-mimicking phantoms,yielding absolute quantification of the concentration of each individual fluorophore.Results are compared to the case when unmixing is performed in the raw 2D data instead of the reconstructed 3D concentration map,showing greater accuracy when unmixing algorithms are applied in the reconstructed data.Both the reflection and transmission geometries are considered.

Recent advances in targeted endoscopic imaging:Early detection of gastrointestinal neoplasms

Molecular imaging has emerged as a new discipline in gastrointestinal endoscopy.This technology encompasses modalities that can visualize disease-specific morphological or functional tissue changes based on the molecular signature of individual cells.Molecular imaging has several advantages including minimal damage to tissues,repetitive visualization,and utility for conducting quantitative analyses.Advancements in basic science coupled with endoscopy have made early detection of gastrointestinal cancer possible.Molecular imaging during gastrointestinal endoscopy requires thedevelopment of safe biomarkers and exogenous probes to detect molecular changes in cells with high specificity anda high signal-to-background ratio.Additionally,a high-resolution endoscope with an accurate wide-field viewing capability must be developed.Targeted endoscopic imaging is expected to improve early diagnosis and individual therapy of gastrointestinal cancer.

Single ultrasmall Mn2＋-doped NaNdF4 nanocrystals as multimodal nanoprobes for magnetic resonance and second near-infrared fluorescence imaging

Multimodal imaging probes have attracted wide attention and have potential to diagnose diseases accurately because of the complementary advantages of multiple imaging modalities. However, intractable issues remain with regard to their complicated multi-step fabrication for hybrid nanostructure and interference of different modal imaging. In the present stud we present, for the first time, T1 and T2-weighted magnetic resonance imaging （MRI） of ultrasmaU Mn2＋-doped NaNdF4 nanocrystals （NCs）, which can also be used simultaneously for second near infrared （NIR-U） fluorescence and computed tomography （CT） imaging, thus enabling high-performance multimodal MRI/NIR-II/CT imaging of single NaNdF4：Mn NCs. The NaNdF4：Mn was demonstrated as a nanoprobe for in vitro and in vivo multimodal MRI and NIR-II fluorescence imaging of human mesenchymal stem cells. The results provide a new strategy to simplify the nanostructure and preparation of probes, based on the features of NaNdF4：Mn NCs, which offer highly efficient multimodal MRI/NIR-II/CT imaging.

聚集诱导发光纳米探针在前列腺癌光热诊疗中的应用

背景:基于“分子内运动受限”这一机制构筑的新型聚集诱导发光荧光探针可用于疾病标志物的检测、肿瘤诊断、细菌成像识别等多个方面。目的:构建基于聚集诱导发光的近红外二区纳米探针FA-DSPE-PEG-AIE@NPs,探讨其用于前列腺癌靶向近红外二区荧光成像及光热治疗的潜能。方法:以卵磷脂、聚乙二醇磷脂、叶酸-聚乙二醇磷脂、聚集诱导发光分子2TT-oC26B为原料,采用纳米沉淀法合成叶酸靶向纳米探针FA-DSPE-PEG-AIE@NPs,对其进行基本表征。选取PC3人前列腺癌细胞、人脐静脉内皮细胞为实验对象,检测纳米探针FA-DSPE-PEG-AIE@NPs的细胞毒性与光照毒性;选取PC3人前列腺癌细胞为实验对象,采用流式细胞术和钙黄绿素/碘化丙啶染色法检测该纳米探针的光热治疗效果。选取BALB/C裸鼠腹部皮下注射PC3人前列腺癌细胞建立肿瘤模型,尾静脉注射纳米探针FA-DSPE-PEG-AIE@NPs后立即对小鼠进行近红外二区荧光成像,12 h后激光照射肿瘤5 min,14 d内观察光热治疗效果。结果与结论:①纳米探针FA-DSPE-PEG-AIE@NPs呈球形,平均粒径(171.0±0.3)nm,具有广谱光吸收能力和延伸至近红外二区的尾部发射,在激光辐照下可发出明亮的近红外二区荧光信号;②纳米探针FA-DSPE-PEG-AIE@NPs的细胞毒性低、光毒性高;流式细胞术及钙黄绿素/碘化丙啶染色法显示,纳米探针FA-DSPE-PEG-AIE@NPs对PC3人前列腺癌细胞具有明显的光热杀伤效果;③纳米探针FA-DSPE-PEG-AIE@NPs成功实现了对活体小鼠血管的近红外二区荧光成像,并确认了在肿瘤部位的最大富集时间为12 h,估算后肢腿部及腹部单根血管的血管宽度分别为0.63 mm和0.42 mm,治疗后14 d小鼠肿瘤体积明显减小;④结果表明,纳米探针FA-DSPE-PEG-AIE@NPs能有效实现前列腺癌的近红外二区荧光成像及光热治疗,有望为前列腺癌的早期诊断及联合治疗提供新手段。

Time-Resolved Imaging in Short-Wave Infrared Region

Compared with the conventional first near-infrared(NIR-I,700900 nm)window,the short-wave infrared region(SWIR,900—1700nm)possesses the merits of the increasing tissue penetration depths and the suppression of scattering background,leading to great potential for in vivo imaging.Based on the limitations of the common spectral domain,and the superiority of the time-dimension,time-resolved imaging eliminates the auto-fuorescence in the biological tissue,thus supporting higher signal-to-noise ratio and sensitivities.The imaging technique is not affected by the difference in tissue composition or thickness and has the practical value of quan-titative in vivo detection.Almost all the relevant time-resolved imaging was carried out around lanthanide-doped upconversion nanomaterials,owing to the advantages of ultralong luminescence lifetime,excellent photostability,controllable morphology,easy surface modification and various strategies of regulating lifetime.Therefore,this review presents the research progress of SWIR time-resolved imaging technology based on nanomaterials doped with lanthanide ions as luminescence centers in recent years.

基于吲哚菁绿的纳米制剂在肿瘤近红外荧光成像和治疗中的应用进展

肿瘤是威胁人类健康的重大疾病之一,早期诊断、治疗是治愈肿瘤的关键。吲哚菁绿(ICG)是一种具有良好光热转换能力的近红外荧光成像染料,可以实现对肿瘤的近红外荧光成像和治疗。近红外荧光成像技术是一种高分辨率和高信噪比成像技术,可利用近红外光(700~1700 nm)及近红外荧光探针检测肿瘤病灶。近年,纳米制剂迅速发展,在疾病诊断和治疗中具有重要意义。ICG与纳米制剂结合不仅可改善ICG稳定性差等问题,还可增强靶向肿瘤病灶的能力。因此,未来深入研究基于ICG纳米制剂在肿瘤近红外荧光成像和治疗中的应用潜力,可以为肿瘤的诊疗提供新思路。

Emerging applications of near-infrared fluorescent metal nanoclusters for biological imaging

Fluorescent metal nanoclusters（MNCs） have recently emerged as a novel kind of promising fluorescent probes for biological imaging because of their ultrasmall core size（〈2 nm）, strong photoluminescence,facile availability and good biocompatibility. In this review, we provide an update on recent advances in the development of near infrared（NIR）-emitting MNCs in terms of synthesis strategies and bioimaging applications. We mainly focus on the utilization of NIR-emitting MNCs（including Au, Ag, Cu and alloy NCs） either as single modal imaging（fluorescence intensity-based imaging, fluorescence lifetime imaging, two-photon imaging） probes or as multimodal imaging（such as NIR fluorescence/X-ray computed tomography/magnetic resonance imaging, NIR fluorescence/photoacoustic imaging/magnetic resonance imaging, NIR fluorescence/single photon emission computed tomography） probes in biological cells and tissues. Finally, we give a brief outlook on the future challenges and prospects of developing NIR-emitting MNCs for bioimaging.

Real-time in vivo visualization of tumor therapy by a near-infrared-II Ag2S quantum dot-based theranostic nanoplatform

Real-time and objective feedback of therapeutic efficacies would be of great value for tumor treatment. Here, we report a smart Ag2S QD-based theranostic nanoplatform （DOX@PEG-Ag2S） obtained by loading the anti-cancer drug doxorubicin （DOX） into polyethylene glycol-coated silver sulfide quantum dots （PEG-Ag2S QDs） through hydrophobic-hydrophobic interactions, which exhibited high drug loading capability （93 wt.% of DOX to Ag2S QDs）, long circulation in blood （t1/2 = 10.3 h）, and high passive tumor-targeting efficiency （8.9% ID/gram） in living mice where % ID/gram reflects the probe concentration in terms of the percentage of the injected dose （ID） per gram of tissue. After targeting the tumor tissue, DOX from PEG-AgRS cargoes was selectively and rapidly released into cancer cells, giving rise to a significant tumor inhibition. Owing to the deep tissue penetration and high spatio-temporal resolution of Ag2S QDs fluorescence in the second near-infrared window （NIR-II）, the DOX@PEG-Ag2S enabled real-time in vivo reading of the drug targeting process and therapeutic efficacy. We expect that such a novel theranostic nanoplatform, DOX@PEG-Ag2S, with integrated drug delivery, therapy and assessment functionalities, will be highly useful for personalized treatments of tumors.