Tumor-homing peptide-based NIR-II probes for targeted spontaneous breast tumor imaging

Fluorescence imaging in the second near-infrared window(NIR-Ⅱ,1000-1700 nm) is a promising modality for real-time imaging of cancer and image-guided surgery with superior in vivo optical properties.So far,very few NIR-Ⅱ fluorophores have been reported for in vivo biomedical imaging of chemically-induced spontaneous breast carcinoma.Herein,a NIR-Ⅱ fluorescent probe CH1055-F3 with the nucleolin-targeted tumor-homing peptide F3 was demonstrated to prefe rentially accumulate in 4 T1 tumors.More importantly,CH1055-F3 exhibited specific NIR-Ⅱ signals with high spatial and temporal resolution,strong tumor uptake,and remarkable NIR-Ⅱ image-guided surgery in dimethylbenzanthracene(DMBA)-induced spontaneous breast tumor rats.This report presents the first tumor-homing peptide-based NIR-Ⅱ probe to diagnose transplantable and spontaneous breast tumors by the active targeting.     

Unlocking multiplexing in deep tissue

<正>In vivo fluorescence imaging in the second near-infrared(NIR-Ⅱ) window (1000–1700 nm) has been emerging as a new powerful imaging technique and demonstrated tremendous potential in life sciences and biomedical applications, given its advances in reducing photon scattering, light absorption, and autofluorescence [1,2]. In particular, ex-     

Polycyclic naphthalenediimide-based nanoparticles for NIR-Ⅱ fluorescence imaging guided phototherapy

Optical imaging and phototherapy in the second near-infrared window(NIR-Ⅱ, 900–1700 nm) can reduce tissue auto-fluorescence and photon scattering, which facilitates higher spatial resolution and deeper tissue penetration depth for solid tumor theranostics. Herein, a polycyclic naphthalenediimide(NDI) based chromophore 13-amino-4,5-dibromo-2,7-di(dodecan-6-yl)-1 H-isoquinolino[4,5,6-fgh]naphtho[1,8-bc][1,9]phenanthroline-1,3,6,8(2H,7H,9H)-tetraone(NDI-NA) was designed and synthesized. With large polycyclic π-systems, NDI-NA molecule possesses broad near-infrared(NIR) absorption(maximum at777 nm) and emission(maximum at 921 nm). By nanoprecipitation, NDI-NA nanoparticles(NPs) were formed in aqueous solution with J-aggregative state, which showed huge red-shift in both absorption spectrum(maximum at 904 nm) and emission spectrum(maximum at 1,020 nm), endowing NDI-NA NPs efficient NIR-Ⅱ fluorescence imaging capability. Besides, the NPs present effective tumor-targeting capability in vivo based on the enhanced permeation and retention(EPR) effect. More importantly, NDI-NA NPs simultaneously have high photothermal conversion efficiency(30.8%) and efficient reactive oxygen species generation ability, making them remarkably phototoxic to cancer cells. The polycyclic chromophore based multifunctional NDI-NA NPs as NIR-Ⅱ phototheranostic agents possess bright future for clinical NIR-Ⅱ imaging-guided cancer phototherapy.     

A novel small-molecule near-infrared II fluorescence probe for orthotopic osteosarcoma imaging

Osteosarcoma is the most common primary malignant tumor of bone, particularly among children and adolescents. Advances in imaging, surgical techniques, and implants have dramatically reduced the need for amputation in the past three decades.Recently, in vivo fluorescence imaging in the second near-infrared window(NIR-II, 1,000–1,700 nm) shows impressive advantages of deeper tissue penetration and higher spatial resolution, which makes it a promising tool for the early diagnosis and post-operative observation of Osteosarcoma. To the best of our knowledge, this paper is the first time to develop a novel NIR-II fluorescence probe conjugated with an osteosarcoma targeted oligopeptide for molecular tumor imaging in a xenograft orthotopic osteosarcoma mouse model.     

Nanoprobes for super-resolution fluorescence imaging at the nanoscale

Compared with other imaging techniques,fluorescence microscopy has become an essential tool to study cell biology due to its high compatibility with living cells.Owing to the resolution limit set by the diffraction of light,fluorescence microscopy could not resolve the nanostructures in the range of<200 nm.Recently,many techniques have been emerged to overcome the diffraction barrier,providing nanometer spatial resolution.In the course of development,the progress in fluorescent probes has helped to promote the development of the high-resolution fluorescence nanoscopy.Here,we describe the contributions of the fluorescent probes to far-field super resolution imaging,focusing on concepts of the existing super-resolution nanoscopy based on the photophysics of fluorescent nanoprobes,like photoswitching,bleaching and blinking.Fluorescent probe technology is crucial in the design and implementation of super-resolution imaging methods.     

NIR-Ⅱ Excitation and NIR-I Emission Based Two-photon Fluorescence Lifetime Microscopic Imaging Using Aggregation-induced Emission Dots

Near-infrared(NIR)lights are powerful tools to conduct deep-tissue imaging since NIR-Ⅰ wavelengths hold less photon absorption and NIR-Ⅱ wavelengths serve low photon scattering in the biological tissues compared with visible lights.Two-photon fluorescence lifetime microscopy(2PFLM)can utilize NIR-Ⅱ excitation and NIR-Ⅰ emission at the same time with the assistance of a well-designed fluorescent agent.Aggregation induced emission(AIE)dyes are famous for unique optical properties and could serve a large two-photon absorption(2PA)cross-section as aggregated dots.Herein,we report two-photon fluorescence lifetime microscopic imaging with NIR-Ⅱ excitation and NIR-Ⅰ emission using a novel deep-red AIE dye.The AIE-gens held a 2PA cross-section as large as 1.61×10⁴GM at 1040 nm.Prepared AIE dots had a two-photon fluorescence peak at 790 nm and a stable lifetime of 2.2 ns under the excitation of 1040 nm femtosecond laser.The brain vessels of a living mouse were vividly reconstructed with the two-photon fluorescence lifetime information obtained by our home-made 2PFLM system.Abundant vessels as small as 3.17μm were still observed with a nice signal-background ratio at the depth of 750μm.Our work will inspire more insight into the improvement of the working wavelength of fluorescent agents and traditional 2PFLM.     

Recent advances on small-molecule fluorophores with emission beyond 1000 nm for better molecular imaging in vivo

In the second near-infrared channel(NIR-II, 1000–1700 nm), organic and inorganic fluorophores are designed with superior chemical/optical properties to provide real-time information with deeper penetration depth and higher resolution owing to the innate lower light scattering and absorption of the NIR-II imaging than conventional optical imaging. Among them, the small-molecule based fluorophores have been highlighted due to their desirable biocompatibility and favorable pharmacokinetics. In this review, we introduced the latest research progress of the rational design of small-molecule NIR-II fluorophores and their impressively biological applications including the NIR-II signal imaging,multimodal imaging and theranostic.     

Boron difluoride formazanate dye for high-efficiency NIR-Ⅱ fluorescence imaging-guided cancer photothermal therapy

The small molecular second near-infrared(NIR-Ⅱ, 1000–1700 nm) dye-based nanotheranostics can concurrently combine deep-tissue photodiagnosis with in situ phototherapy, which occupies a vital position in the early detection and precise treatment of tumors. However, the development of small molecular NIR-Ⅱ dyes is still challenging due to the limited electron acceptors and cumbersome synthetic routes.Herein, we report a novel molecular electron acceptor, boron difluoride formazanate(BDF). Based on...     

Donor-Acceptor Typed AIE Luminogens with Near-infrared Emission for Super-resolution Imaging

Aggregation-induced emission(AIE)luminogens(AIEgens)with high brightness in aggregates exhibit great potentials in biological imaging,but these AIEgens are seldom applied in super-resolution biological imaging,especially in the imaging by using the structural illumination microscope(SIM).Based on this consideration,we synthesized the donor-acceptor typed AIEgen of DTPA-BTN,which not only owns high brightness in the near-infrared(NIR)emission region from 600 nm to 1000 nm(photoluminescence quantum yield,PLQYs=11.35%),but also displays excellent photo-stability.In addition,AIE nanoparticles based on 4,7-ditriphenylamine-[1,2,5]-thiadiazolo[3,4-c]pyridine(DTPA-BTN)were also prepared with highly emissive features and excellent biocompatibility.Finally,the developed DTPA-BTN-based AIE nanoparticles were applied in the super-resolution cellular imaging via SIM,where much smaller full width at half-maximum values and high signal to noise ratios were obtained,indicating the superior imaging resolution.The results here imply that highly emissive AIEgens or AIE nanoparticles can be promising imaging agents for super-resolution imaging via SIM.     

Recognition of ClO－ and Cellular Imaging with Xanthene-based Fluorescent Probes北大核心CSCD

Selective recognition of hypochlorite ion（ClO－）in intracellular biological environment is important for research and application in cellular physiology and pathology. A novel fluorescent molecule, 6-bis （dimethylamino）-9-（1-（3-methyl-benzothiazole）-trimethyl）-xanthene（R-1）,is designed and synthesized with a combination of dimethylamino-substituted xanthene and benzothiazole segments through continuous carbon-carbon double bonds. In the presence of ClO－ ,the fluorescence emission of R-1 at 600 nm is significantly enhanced（the quantum yield is as high as 20. 3%）,and other reactive oxygen species do not affect the recognition of ClO－. Fluorescence imaging experiments demonstrate that probe R-1 can detect ClO－ in human lung adenocarinoma （A549）cells and emit red fluorescence,indicating the potential application of R-1 in ClO－ biological imaging. © 2022, Science Press (China). All rights reserved.     

稀土纳米材料在高分辨活体成像及诊疗中的应用

荧光成像具有时空分辨率高、 反馈快、 非侵入和无电离辐射等优点, 是一种重要的生物成像技术. 与传统用于荧光成像的可见光和近红外一区(NIR-I, 600~950 nm)相比, 近红外二区(NIR-Ⅱ, 1000~1700 nm)窗口具有低生物组织散射系数和低生物自发荧光, 采用NIR-Ⅱ光进行活体荧光成像能有效提高成像的分辨率、 信噪比和穿透深度. 稀土纳米颗粒(RENPs)具有大斯托克斯位移、 高化学稳定性、 可调的荧光寿命以及较窄的发射带, 是一种重要的荧光成像探针. 近年来, 一系列具有优异的NIR-Ⅱ发光性能的稀土纳米材料被用于高分辨活体荧光成像. 本文综合评述了近年来RENPs用于高分辨活体成像及诊疗中的研究进展, 概述了RENPs的掺杂调控、 基质晶格选择和复合敏化等NIR-Ⅱ发光增强策略, 介绍了其在多种生物医学场景中的靶向聚集、 荧光传感和疾病治疗等功能, 并总结了其在多路成像、 多模态成像和疾病诊疗中的应用. 最后, 简要分析了RENPs在未来生物医学应用中面临的挑战和发展的方向.     

近红外二区活体荧光成像在肿瘤诊疗中的应用

由于具备组织穿透深度深和时空分辨率高等优势, 近年来近红外二区(Near-infrared-Ⅱ, NIR-Ⅱ, 1000~1700 nm)荧光成像技术得到了快速发展, 其在肿瘤临床诊断和治疗的潜力更是引发了广泛关注. 本文首先阐释了NIR-Ⅱ窗口荧光成像的原理及其优势, 随后根据结构分类归纳总结了现有荧光团的特征, 重点介绍了荧光探针在性能优化上的进展以及在肿瘤早期检测、 术中导航和光疗中的应用, 最后讨论了现有NIR-Ⅱ 荧光探针的局限以及临床转化面临的挑战, 并对未来的发展方向进行了展望.     

Cr,In共掺杂MgGa2O4小尺寸近红外长余辉纳米颗粒的制备及发光性能

采用乙二醇辅助共沉淀法制备了小尺寸Cr,In共掺杂MgGa₂O₄(MGO∶Cr, In)近红外长余辉发光纳米粒子(Persistent luminescence nanoparticles, PLNPs), 并考察了Cr, In共掺杂及煅烧温度对MGO晶体结构、 余辉发光性质和尺寸的影响. 结果表明, 最优Cr, In共掺杂浓度分别为0.3%和0.02%, MGO∶Cr, In晶体属于Fd3m空间群, Cr, In共掺杂对纳米颗粒的结构无影响, 平均粒径为(8.61±2.23) nm, 分散性良好, 最佳煅烧温度为700 ℃. 并且, In掺杂可有效延长其余辉发光寿命, 平均发光寿命(τ_av)从49.33 s增大至52.89 s; 荧光量子产率增高至44.9%; 活化能E_a为(0.36±0.04) eV, 具有良好的热稳定性; 陷阱深度为0.696 eV. 此外, 该PLNPs分别在260 nm、410 nm和600 nm处有激发峰, 表明UV光、 蓝绿光以及红光皆可实现对其的激发, 发射波长皆位于705 nm处, 属于Cr³⁺的²E(²G)→⁴A₂(⁴F)跃迁. 该PLNPs在红色LED灯、 光学储器件以及生物医学等领域具有巨大潜在应用价值.     

水溶性近红外Ⅱ区荧光Ag2Te量子点的合成

量子点具有独特的光学性质, 在生物医学领域有着广泛的应用. Ag₂Te作为Ⅰ-Ⅵ族量子点中的一员, 因具有生物毒性小和带隙窄等优势而备受关注, 但是目前直接合成水溶性Ag₂Te量子点的方法较少, 而且可调节的荧光发射波长范围有限. 本文提出了一种合成荧光发射波长位于近红外Ⅱ区窗口的水溶性Ag₂Te量子点的新方法. 该方法以硝酸银为银前体, N-乙酰-L-半胱氨酸为配体, 碲前体利用硼氢化钠还原亚碲酸钠得到, 反应条件温和(室温、 大气氛围)且不涉及有毒的有机试剂, 绿色环保. 通过进一步的阳离子处理钝化其表面缺陷, 可以得到尺寸均一的超小粒径水溶性Ag₂Te量子点, 量子点的荧光发射波长为1160 nm, 量子产率为8.0% (以IR26染料为参照). 该方法所合成的Ag₂Te量子点具有良好的生物相容性, 注入小鼠体内后能观察到明显的近红外荧光, 具有进一步生物应用的潜力.     

基于共轭聚合物的纳米粒子用于肿瘤的近红外二区荧光成像及光热治疗

为提高生物组织荧光成像质量以及对肿瘤的高效光热治疗,设计合成了一种新型的窄带隙共轭聚合物(BDT-TTQ),并通过纳米沉积的方式将聚合物制备成水溶性纳米粒子(BDT-TTQ NPs).该共轭聚合物纳米粒子在1000~1200 nm近红外二区范围具有较好的吸收,在1064 nm的激发光下能实现1200~1400 nm的近红外二区荧光成像. BDT-TTQ NPs纳米粒子粒径分布较窄,形貌呈规则的球形且分散均匀,具有好的生物相容性.该纳米粒子既可以在体外实现较高的近红外二区荧光成像穿透深度,又可以实现对小鼠活体血管的高清晰度的近红外二区荧光成像.此外,BDT-TTQ NPs纳米粒子在1064 nm激光下展现出优异的光热转换效率,具有较高的光毒性,对体外的肿瘤细胞以及小鼠的异质瘤具有高的光热杀伤能力.     

溶酶体靶向吲哚氟硼二吡咯光敏剂的合成、 双光子荧光成像及光动力治疗

通过Knoevenagel缩合反应制备了一个具有溶酶体靶向的近红外光敏剂IMBDP-Lys, 用于双光子荧光成像和光动力治疗. IMBDP-Lys由2个吲哚吗啉功能团连接到氟硼二吡咯(BODIPY)母核的3?位和8?位构筑而成, 是一种重原子诱导的光敏剂. 采用高斯09W理论计算光敏剂S₁态和T₂态能量值相差0.12 eV, 可以有效地发生系间窜越. 在二氯甲烷溶液中, 光敏剂IMBDP-Lys的最大吸收波长为631 nm, 最大发射波长为684 nm. 在 660 nm的光照下, 以亚甲基蓝为参比, 单线态氧量子产率经计算为48.3%. 此外, 含有2个吗啉基团的光敏剂IMBDP-Lys具有良好的生物相容性和精准的靶向能力, 可以快速地进入斑马鱼体内进行双光子荧光成像, 并且与溶酶体绿色染料Lyso-Tracker Green共定位系数为0.95. 溴化噻唑蓝四氮唑(MTT)实验结果表明, 光敏剂具有低的暗毒性(≥85%)和高的光毒性(IC₅₀=0.52 μmol/L). 在660 nm的光照下, 利用活性氧荧光探针2’,7’-二氯二氢荧光素二乙酸酯（DCFH-DA）证明光敏剂可以产生活性氧, 同时吖啶橙/溴化乙锭(AO/EB)染色实验和细胞迁移实验表明产生的活性氧不仅能诱导A549细胞凋亡, 还能有效地抑制肿瘤细胞迁移. 因此, 近红外光敏剂IMBDP-Lys在双光子荧光成像和溶酶体靶向的光动力治疗中具有重要的应用价值.     

小分子基温敏聚合物纳米粒子的制备及在近红外二区荧光成像与光热治疗中的应用

以有机小分子4,9-二(5-9H-芴-2-基-噻吩-2-基)-6',7-联苯[1,2,5]噻二唑并[3,4-g]喹喔啉(TQF)为前驱体, 通过化学方法将其修饰为可引发可逆加成-断裂链转移聚合(RAFT)反应的小分子链转移剂TQF-苯基硫代链 转移剂（CTA）. 以TQF-CTA为链转移剂, 以偶氮二异丁腈为引发剂, 引发N-异丙基丙烯酰胺(NIPAAm)和 甲基丙烯酸寡聚乙二醇酯(OEGMA)发生RAFT聚合反应, 合成了具有良好水溶性和较低临界溶解温度(LCST)的小分子基共聚物[TQF-P(NIPAAm-co-OEGMA), TPNO]. 将其直接溶于水中可制备成温敏的球形纳米粒子 TPNO NPs. 研究结果表明, TPNO NPs在温度大于LCST(35 ℃)时表现出一个明显的粒径变化和显著的荧光 增强行为(2.2倍), 并成功实现了对活体小鼠血管与肿瘤的明亮近红外二区(NIR-Ⅱ)荧光成像(FI). 同时, TPNO NPs有着良好的光热转换效率(PCE=29.8%), 通过体外细胞实验证明了其对细胞具有较好的光热治疗(PTT)效果.     

碰撞能对K(2S)+HF(X1Σ+)→KF(X1Σ+)+H(2S)反应的影响

基于Sayós等构建的基态势能面, 运用准经典轨线方法对原子-分子反应K(²S)+HF(X¹∑⁺)→KF(X¹∑⁺)+ H(²S)的立体动力学性质进行了研究. 计算了该反应的极化微分反应截面、 两矢量k?j'相关分布函数P(θ_r)、 三矢量k?k'?j'相关分布函数P(?_r)和空间分布函数P(θ_r,?_r). 结果表明, 产物KF的转动角动量j′不仅在垂直于反应物相对速度矢量k的方向上有强烈的取向效应, 而且还定向于y轴的负方向, 转动角动量j′敏感地依赖于碰撞能.     

三联吡啶化合物的溶剂致荧光变色及丁醇异构体鉴别

在三联吡啶分子中引入N,N-二甲基官能团, 实现了三联吡啶分子的局部激发态发光. 研究发现, 溶剂的极性诱导三联吡啶的偶极矩发生变化, 实现了从深蓝光(λ_max=384 nm)到黄光(λ_max=558 nm)的溶剂致荧光变色. 由于三联吡啶的荧光易受醇溶剂中—OH基团振荡猝灭, 不同空间位阻的正丁醇、 异丁醇、 仲丁醇及叔丁醇溶剂使得三联吡啶发光光色相近, 但发光强度的差异较大. 三联吡啶进一步与ZnCl₂配位得到了三联吡啶-Zn(Ⅱ)配合物, 金属离子Zn(Ⅱ)的配位作用促进了三联吡啶分子内电荷转移. 由于电子给体N,N-二甲基官能团可发生平面扭曲, 丁醇异构体可调节三联吡啶-Zn(Ⅱ)的局部激发态和扭曲分子内电荷转移发光, 进而实现其在丁醇异构体溶剂中发光光色的调节. 因此, 三联吡啶和三联吡啶-Zn(Ⅱ)具有良好的溶剂致荧光变色性能, 可应用于4种丁醇异构体的鉴别.     

一种新的镧系金属有机骨架材料的合成、 结构及荧光检测性质

利用溶剂热方法合成了一种以Tb³⁺离子为中心的金属有机骨架材料［Tb₂(bpt)₂(H₂O)₂］·(DMA)_4.5, 并通过单晶X射线衍射(SXRD)、 粉末X射线衍射(PXRD)、 元素分析(EA)、 热重分析(TGA)、 傅里叶变换红外光谱 (FTIR)以及荧光光谱技术(FS)表征了该材料的结构与基本物理化学性质. 单晶衍射分析结果显示该材料具有包含一维直孔道的三维结构, 结构中孔道窗口尺寸约为1.23 nm×1.10 nm. 荧光分析测试结果表明该材料对Cr³⁺离子有荧光响应, 离子检测限低至0.22 mg/L, 同时具有良好的选择性, 在Cr³⁺离子的荧光检测领域具有重要的应用潜力.