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Pub Date : 2025-03-24
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引用次数: 0
Signal Transduction Strategies for DNAzyme-Based Sensing and Imaging of Metal Ions in Cells and in Vivo 基于dnazyme的金属离子在细胞和体内传感和成像的信号转导策略
IF 5.7 Pub Date : 2025-03-20 DOI: 10.1021/cbmi.4c00090
Whitney Lewis, Annie Farrell, Shreestika Pradhan and Yi Lu*, 

Metal ions play crucial roles in biological processes, and their dysregulation can lead to various diseases. Understanding the distribution of these metal ions provides deeper insight into their roles in both health and disease. DNAzymes offer a general approach for detecting nearly any metal ion within cells and in vivo with high sensitivity and selectivity, including different oxidation states of the same metal ion. This Review summarizes recent developments in signal transduction strategies for DNAzyme-based sensing and imaging of metal ions in living cells and in vivo. We examine various signal transduction strategies to convert metal ion binding by DNAzymes into measurable signals. These strategies include fluorescence imaging using small molecules, nanostructures and nanoparticles, motors and machines, and other fluorescent materials as well as bioluminescence imaging. We then provide recent examples of applying these DNAzyme-based fluorescence or bioluminescence imaging methods to understand metal ion dynamics and their roles in diseases in living cells and in vivo. Finally, we discuss future directions for advancing intracellular and in vivo metal ion imaging using DNAzymes.

金属离子在生物过程中起着至关重要的作用,其失调可导致多种疾病。了解这些金属离子的分布可以更深入地了解它们在健康和疾病中的作用。DNAzymes提供了一种检测细胞内和体内几乎任何金属离子的通用方法,具有高灵敏度和选择性,包括同一金属离子的不同氧化态。本文综述了在活细胞和体内基于dnazyme的金属离子传感和成像信号转导策略方面的最新进展。我们研究了各种信号转导策略,将DNAzymes的金属离子结合转化为可测量的信号。这些策略包括荧光成像使用小分子,纳米结构和纳米粒子,电机和机器,以及其他荧光材料,以及生物发光成像。然后,我们提供了最近应用这些基于dnazyme的荧光或生物发光成像方法来了解金属离子动力学及其在活细胞和体内疾病中的作用的例子。最后,我们讨论了利用DNAzymes推进细胞内和体内金属离子成像的未来方向。
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引用次数: 0
Positron Emission Tomography Imaging of the Adaptive Immune System in Cardiovascular Diseases. 心血管疾病中适应性免疫系统的正电子发射断层成像。
Pub Date : 2025-03-19 eCollection Date: 2025-04-28 DOI: 10.1021/cbmi.4c00117
Jaume Ramon Otaegui, Deborah Sultan, Gyu Seong Heo, Yongjian Liu

Cardiovascular diseases are the leading cause of death around the globe. In recent years, a crucial role of the immune system has been acknowledged in cardiac disease progression, opening the door for immunomodulatory therapies. To this ongoing change of paradigm, positron emission tomography (PET) imaging of the immune system has become a remarkable tool to reveal immune cell trafficking and monitor disease progression and treatment response. Currently, PET imaging of the immune system in cardiovascular disease mainly focuses on the innate immune system such as macrophages, while the immune cells of the adaptive immune system including B and T cells are less studied. This can be ascribed to the lack of radiotracers specifically binding to B and T cell biomarkers compatible with PET imaging within the cardiovascular system. In this review, we summarize current knowledge about the role of the adaptive immune system (e.g., B and T cells) in major cardiovascular diseases and introduce key biomarkers for specific targeting of these immune cells and their subpopulations. Finally, we present available radiotracers for these biomarkers and propose a pathway for developing probes or optimizing those already used in other fields (e.g., oncology) to make them compatible with the cardiovascular system.

心血管疾病是全球死亡的主要原因。近年来,免疫系统在心脏病进展中的关键作用已被承认,为免疫调节疗法打开了大门。随着这种范式的不断变化,免疫系统的正电子发射断层扫描(PET)成像已成为揭示免疫细胞运输和监测疾病进展和治疗反应的重要工具。目前,心血管疾病免疫系统的PET成像主要集中在巨噬细胞等先天免疫系统,而对B细胞、T细胞等适应性免疫系统的免疫细胞研究较少。这可以归因于缺乏与心血管系统内PET成像兼容的B细胞和T细胞生物标志物特异性结合的放射性示踪剂。在这篇综述中,我们总结了目前关于适应性免疫系统(如B细胞和T细胞)在主要心血管疾病中的作用的知识,并介绍了特异性靶向这些免疫细胞及其亚群的关键生物标志物。最后,我们提出了这些生物标志物的可用放射性示踪剂,并提出了开发探针或优化已在其他领域(例如肿瘤学)使用的探针的途径,以使其与心血管系统兼容。
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引用次数: 0
Peroxynitrite Responsive Second Near-Infrared Cyanine Dye J‑Aggregate for Drug-Induced Hepatotoxicity Monitoring. 过氧亚硝酸盐响应第二近红外菁染料J -聚集体用于药物诱导的肝毒性监测。
Pub Date : 2025-03-18 eCollection Date: 2025-06-23 DOI: 10.1021/cbmi.4c00111
Kun Wu, Zhicong Chao, Subi Aji, Yu Zhu, Hongxia Zhao, Ying An, Huangxian Ju, Ying Liu

Drug-induced hepatotoxicity is a long-standing concern of modern medicine. The production of peroxynitrite (ONOO-) is proposed as an early sign of the progression of drug-induced hepatotoxicity. However, conventional blood tests fail to offer a real-time unambiguous visualization of such hepatotoxicity in vivo. ONOO- probes that are currently reported are mainly located in the visible or the first near-infrared (NIR-I) window, which have limited in vivo biosensing application due to the autofluorescence and photon scattering. Here, we report an ONOO- responsive cyanine dye, IR-1061 J-aggregate (J IR-1061), which exhibits a red shift over 500 nm, with an absorption peak at 1580 nm in the NIR-IIb region. By conjugating J IR‑1061 with rare earth nanoparticles (RENPs) that have NIR-IIb emission at 1550 nm, a dual-mode imaging probe RENPs-J IR‑1061 is developed. RENPs-J IR‑1061 shows a fast and sensitive response to ONOO-, with activatable NIR-IIb fluorescence and a change in the photoacoustic signals, which is successfully applied for real-time monitoring of hepatotoxicity in vivo.

药物性肝毒性是现代医学长期关注的问题。过氧亚硝酸盐(ONOO-)的产生被认为是药物性肝毒性进展的早期迹象。然而,传统的血液检查不能提供这种肝毒性在体内的实时、明确的可视化。目前报道的ONOO-探针主要位于可见光或第一个近红外(NIR-I)窗口,由于其自身荧光和光子散射,限制了其在体内生物传感中的应用。本文报道了一种对ONOO有响应的菁菁染料IR-1061 J-aggregate (J IR-1061),它表现出500 nm以上的红移,在NIR-IIb区有一个1580 nm的吸收峰。通过将jir - 1061与NIR-IIb发射波长为1550 nm的稀土纳米粒子(RENPs)偶联,研制了一种双模成像探针RENPs- jir - 1061。RENPs-J IR- 1061对ONOO-具有快速灵敏的响应,具有可激活的NIR-IIb荧光和光声信号的变化,成功地应用于体内肝毒性的实时监测。
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引用次数: 0
Probing Electrochemical Strain Generation in Vanadium Oxide Cathodes during Cycling of Aqueous Zinc-Ion Batteries via Imaging Technique. 利用成像技术探测锌离子电池循环过程中氧化钒阴极产生的电化学应变。
Pub Date : 2025-03-16 eCollection Date: 2025-06-23 DOI: 10.1021/cbmi.5c00003
Bret A Marckx, Hunter Maclennan, Ömer Özgür Capraz

Aqueous batteries have received a great deal of attention for grid-scale energy storage applications but suffer from low-capacity retention and utilization. A lack of understanding of chemomechanical instabilities and charge storage mechanisms in cathodes limits the development of advanced aqueous batteries. To shed light on these instabilities, operando techniques are necessary to probe the complex interplay between electrochemistry and mechanics during cycling. Here, we report an operando technique to probe electrochemical strains in cathodes in aqueous electrolytes during battery cycling via optical imaging and digital image correlation. Operando mechanical measurements indicate that the cathode undergoes positive strain generation during discharge and negative generation during charge. Strain derivatives reveal a close correlation between electrochemical and mechanical behaviors, highlighting the connection between electrochemistry and mechanics. This operando imaging technique is broadly applicable and paves the way for a deeper understanding of deformation mechanisms in aqueous, multivalent ion battery materials.

水溶液电池在电网规模的储能应用中受到了广泛的关注,但存在容量保持和利用率低的问题。缺乏对阴极化学力学不稳定性和电荷储存机制的理解限制了先进水电池的发展。为了阐明这些不稳定性,有必要利用operando技术来探索循环过程中电化学和力学之间复杂的相互作用。在这里,我们报告了一种operando技术,通过光学成像和数字图像相关来探测电池循环过程中水溶液电解质阴极的电化学应变。Operando力学测量表明,阴极在放电时产生正应变,在充电时产生负应变。应变导数揭示了电化学和力学行为之间的密切联系,突出了电化学和力学之间的联系。这种operando成像技术广泛适用,为更深入地理解水、多价离子电池材料的变形机制铺平了道路。
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引用次数: 0
Impact of Droplet Wettability on Scanning Electrochemical Cell Microscopy Performance in Stainless Steels. 液滴润湿性对不锈钢扫描电化学显微镜性能的影响。
Pub Date : 2025-03-13 eCollection Date: 2025-04-28 DOI: 10.1021/cbmi.4c00101
Sarah R Yassine, León Zendejas Medina, Egor Katkov, Robert Lacasse, Janine Mauzeroll

Variations in droplet wettability affect localized corrosion during scanning electrochemical cell microscopy (SECCM) on stainless steel. The droplet dynamics are influenced by stainless-steel microstructural features and surface conditions-such as surface roughness, inclusions, and the addition of an oil layer. As opposed to previous work on aluminum alloys, droplet spreading is promoted by oil immersion, which leads to an increase in the cathodic currents. Rougher surfaces hinder droplet spreading, largely due to the droplet pinning effect, and exhibit higher pitting corrosion incidences compared to smoother surfaces. Moreover, the presence of inclusions intensifies pitting initiation and constrains the landing area (droplet size). We report that while the landing area does not affect the number of metastable pits, small landing areas lead to a high probability of stable pitting.

在扫描电化学电池显微镜(SECCM)中,液滴润湿性的变化影响不锈钢的局部腐蚀。液滴动力学受不锈钢微观结构特征和表面条件(如表面粗糙度、夹杂物和油层的添加)的影响。与之前对铝合金的研究相反,油浸会促进液滴的扩散,从而导致阴极电流的增加。粗糙的表面阻碍了液滴的扩散,这主要是由于液滴的钉住效应,与光滑的表面相比,粗糙的表面表现出更高的点蚀发生率。此外,夹杂物的存在加剧了点蚀的发生并限制了着陆面积(液滴尺寸)。我们报道,虽然着陆面积不影响亚稳坑的数量,但较小的着陆面积导致稳定点蚀的概率很高。
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引用次数: 0
Real-Time Visualization of Endogenous H2O2 Production in Mammalian Spheroids by Electrochemiluminescence. 利用电化学发光技术实时可视化哺乳动物球体内源性H2O2生成。
Pub Date : 2025-03-10 eCollection Date: 2025-05-26 DOI: 10.1021/cbmi.4c00105
Vanshika Gupta, Francesco Falciani, Brady R Layman, Megan L Hill, Stefania Rapino, Jeffrey E Dick

Two-dimensional cell culture may be insufficient when it comes to understanding human disease. The redox behavior of complex, three-dimensional tissue is critical to understanding disease genesis and propagation. Unfortunately, few measurement tools are available for such three-dimensional models to yield quantitative insight into how reactive oxygen species (ROS) form over time. Here, we demonstrate an imaging platform for the real-time visualization of H2O2 formation for mammalian spheroids made of noncancerous human embryonic kidney cells (HEK-293) and metastatic breast cancer cells (MCF-7 and MDA-MB-231). We take advantage of the luminol and H2O2 electrochemiluminescence reaction on a transparent tin-doped indium oxide electrode. The luminescence of this reaction as a function of [H2O2] is linear (R 2 = 0.98) with a dynamic range between 0.5 μM to 0.1 mM, and limit of detection of 2.26 ± 0.58 μM. Our method allows for the observation of ROS activity in growing spheroids days in advance of current techniques without the need to sacrifice the sample postanalysis. Finally, we use our procedure to demonstrate how key ROS pathways in cancerous spheroids can be up-regulated and downregulated through the addition of common metabolic drugs, rotenone and carbonyl cyanide-p-trifluoromethoxyphenylhydrazone. Our results suggest that the Warburg Effect can be studied for single mammalian cancerous spheroids, and the use of metabolic drugs allows one to implicate specific metabolic pathways in ROS formation. We expect this diagnostic tool to have wide applications in understanding the real-time propagation of human disease in a system more closely related to human tissue.

在了解人类疾病方面,二维细胞培养可能是不够的。复杂的三维组织的氧化还原行为对理解疾病的发生和传播至关重要。不幸的是,很少有测量工具可用于这种三维模型,以定量了解活性氧(ROS)如何随时间形成。在这里,我们展示了一个用于实时可视化由非癌性人胚胎肾细胞(HEK-293)和转移性乳腺癌细胞(MCF-7和MDA-MB-231)组成的哺乳动物球体H2O2形成的成像平台。我们利用发光氨和H2O2在透明锡掺杂氧化铟电极上的电化学发光反应。该反应的发光与[H2O2]呈线性关系(r2 = 0.98),动态范围为0.5 μM ~ 0.1 mM,检出限为2.26±0.58 μM。我们的方法允许在生长的球体中观察ROS活性,比当前技术提前几天,而不需要牺牲样品的后分析。最后,我们使用我们的程序来演示如何通过添加常见的代谢药物,鱼tenone和羰基氰化物-对三氟甲氧基苯腙上调和下调癌球体中的关键ROS通路。我们的研究结果表明,Warburg效应可以在单个哺乳动物癌性球体中进行研究,并且使用代谢药物可以在ROS形成中暗示特定的代谢途径。我们期望这种诊断工具在了解人类疾病在与人体组织更密切相关的系统中的实时传播方面具有广泛的应用。
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引用次数: 0
Single-Molecule Fluorescence Imaging of Energy-Related Catalytic Reactions. 能量相关催化反应的单分子荧光成像。
Pub Date : 2025-03-07 eCollection Date: 2025-05-26 DOI: 10.1021/cbmi.4c00112
Qingdian Yan, Xianghong Li, Jianbin Luo, Ming Zhao

The pressing challenges of the energy crisis and environmental problems necessitate the pursuit of efficient and sustainable energy conversion technologies, wherein catalytic processes play a vital role in addressing these issues. Single-molecule fluorescence microscopy (SMFM) offers a transformative approach to understanding various catalytic reactions by enabling real-time visualization of molecular adsorption, diffusion, and transformation on catalytic surfaces. The unprecedented insights into the spatial distribution of active sites, catalytic heterogeneity, and the dynamics of key intermediates result in single- or subparticle level structure-property relations, thereby offering insightful perspectives for catalyst design and mechanistic understanding of energy-related catalytic processes. In this review, we provide an overview of the recent progress in using SMFM for investigating energy-related catalytic reactions. The advancement in SMFM imaging techniques for investigating nonfluorescent chemical processes is also highlighted. Finally, we conclude the review by commenting on the current challenges and prospects in advancing SMFM in energy research. We hope that the capable SMFM imaging techniques and insights will promote the development and realistic application of various energy-related catalytic reactions, together with inspiring researchers to explore the power of SMFM in other applications.

能源危机和环境问题的紧迫挑战要求追求高效和可持续的能源转换技术,其中催化过程在解决这些问题方面起着至关重要的作用。单分子荧光显微镜(SMFM)提供了一种变革性的方法,通过使分子吸附、扩散和催化表面转化的实时可视化来理解各种催化反应。对活性位点的空间分布、催化非均质性和关键中间体动力学的前所未有的见解导致了单或亚颗粒水平的结构-性质关系,从而为催化剂设计和能源相关催化过程的机理理解提供了深刻的见解。在这篇综述中,我们概述了利用SMFM研究能源相关催化反应的最新进展。研究非荧光化学过程的SMFM成像技术的进步也得到了强调。最后,我们对SMFM在能源研究中面临的挑战和前景进行了总结。我们希望SMFM成像技术和见解能够促进各种能源相关催化反应的发展和实际应用,并激励研究人员探索SMFM在其他应用中的力量。
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引用次数: 0
Nonlight-Driven Aggregation-Induced Emission Luminogens for Bioimaging and Theranostics. 用于生物成像和治疗的非光驱动聚集诱导发射发光源。
Pub Date : 2025-03-04 eCollection Date: 2025-06-23 DOI: 10.1021/cbmi.4c00108
Yong Tian, Weigeng Huang, Zhijia Sheng, Dingyuan Yan, Dong Wang, Ben Zhong Tang

Aggregation-induced emission luminogens (AIEgens) have been prosperously developed and applied in the fields of optical imaging and theranostics since its establishment. Nowadays, AIEgens can fulfill nearly all requirements in optical imaging and theranostics with emission spectra ranging from visible to near-infrared wavelengths. Although a variety of AIEgens with varying wavelengths and functionalities have been continuously designed, their performance is heavily dependent on the use of conventional light sources, such as xenon lamps and lasers, which severely hinder further applications due to limited penetration depth and background autofluorescence in biological tissues. To mitigate these limitations and maximize the potential of AIEgens, unconventional excitation sources such as chemical energy, ultrasound, and X-ray offer effective alternatives that circumvent the drawbacks associated with traditional light-based constant excitation. In this Review, we introduce the fundamental principles governing the combination of unconventional excitation sources with AIEgens, highlight recent advancements in using AIEgens excited by these unconventional sources for bioimaging and theranostics, and discuss current challenges and future perspectives aimed at advancing the biomedical applications of AIEgens.

聚集体致发光光源自问世以来,在光学成像和治疗领域得到了蓬勃的发展和应用。如今,AIEgens几乎可以满足光学成像和治疗学的所有要求,其发射光谱范围从可见光到近红外波长。尽管不断设计出各种具有不同波长和功能的AIEgens,但其性能严重依赖于传统光源的使用,如氙灯和激光,由于生物组织中的穿透深度和背景自身荧光有限,这严重阻碍了进一步的应用。为了减轻这些限制并最大限度地发挥AIEgens的潜力,非常规的激发源,如化学能、超声波和x射线,提供了有效的替代方案,绕过了传统的基于光的恒定激发相关的缺点。在这篇综述中,我们介绍了非常规激励源与AIEgens结合的基本原理,重点介绍了利用这些非常规激励源激发的AIEgens进行生物成像和治疗的最新进展,并讨论了当前的挑战和未来的展望,旨在推进AIEgens的生物医学应用。
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引用次数: 0
Albumin Encapsulation of Cyanine Dye for High-Performance NIR-II Imaging-Guided Photodynamic Therapy 高效NIR-II成像引导光动力治疗中花青素染料白蛋白包封。
IF 5.7 Pub Date : 2025-03-04 DOI: 10.1021/cbmi.5c00005
Lang Bai, Yiyang Jia, Zihan Wang, Zeen Wang, Yunlong Jia, Yuewei Zhang and Shoujun Zhu*, 

Albumin encapsulation is a powerful strategy for drug delivery, yet its potential has not been fully explored for photodynamic therapy (PDT) agents. Cl-containing near-infrared (NIR) cyanine dyes are intrinsically PDT agents and tend to covalently bind with albumin; however, their PDT efficiency in tumors is largely compromised due to limited accumulation of the complex (size less than 10 nm) to the tumor site. To maximize their PDT effect while retaining sufficient NIR brightness for imaging-guided PDT, we developed a DTT-promoted encapsulation strategy to enhance singlet oxygen release for Cl-containing dyes. By disrupting disulfide bonds in albumin, the protein shell is loosened, increasing size while maintaining singlet oxygen release, partial brightness, and photostability. In vivo experiments reveal the rapid tumor accumulation of IR-6B3@DTT-HSA, enabling flexible treatment timing. This strategy enhances targeted delivery and PDT efficacy, paving the way for broader applications in cancer therapy.

白蛋白包封是一种强大的药物递送策略,但其在光动力治疗(PDT)药物中的潜力尚未得到充分的探索。含氯近红外(NIR)菁染料本质上是PDT试剂,倾向于与白蛋白共价结合;然而,由于复合物(尺寸小于10 nm)在肿瘤部位的有限积累,它们在肿瘤中的PDT效率在很大程度上受到损害。为了最大限度地提高PDT效果,同时为成像引导PDT保留足够的近红外亮度,我们开发了一种dtt促进封装策略,以增强含cl染料的单线态氧释放。通过破坏白蛋白中的二硫键,蛋白质外壳松动,增加尺寸,同时保持单线态氧释放,部分亮度和光稳定性。体内实验显示IR-6B3@DTT-HSA的肿瘤快速积累,使治疗时机灵活。这一策略增强了靶向递送和PDT疗效,为更广泛地应用于癌症治疗铺平了道路。
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引用次数: 0
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Chemical & Biomedical Imaging
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