Bioimaging

生物成像
  • 文章类型: Journal Article
    纳米医学是一门医学学科,它将纳米技术策略和概念的各个方面应用于治疗和筛查的可能性。合成聚合物纳米结构是由于其作为载体的潜力而经常研究的许多纳米药物制剂之一。生物成像是一种有价值的诊断工具,因此,总是需要新的赋形剂/纳米载体。在这项研究中,疏水性超支化聚(甲基丙烯酸月桂酯)(PLMA)均聚物由具有-COOH极性端基的高度疏水性LMA部分组成,通过采用可逆加成-断裂链转移(RAFT)聚合来合成。乙二醇二甲基丙烯酸酯(EGDMA)用作支化剂。通过所使用的RAFT剂引入端基。所得两亲性超支化聚合物通过尺寸排阻色谱(SEC)进行分子表征,傅里叶变换红外光谱(FT-IR),和1H-NMR光谱。芘,姜黄素,和IR-1048染料是成功包封的疏水性有效载荷分子,以显示这些均聚物纳米颗粒(通过在水中的纳米沉淀制备)作为染料纳米载体的适应性。这项研究证明了一种简单的方法,通过从两亲性,超支化,疏水均聚物,具有低比例的极性端基,用于生物成像目的。
    Nanomedicine is a discipline of medicine that applies all aspects of nanotechnology strategies and concepts for treatment and screening possibilities. Synthetic polymer nanostructures are among the many nanomedicine formulations frequently studied for their potential as vectors. Bioimaging is a valuable diagnostic tool, thus, there is always a demand for new excipients/nanocarriers. In this study, hydrophobic hyperbranched poly(lauryl methacrylate) (PLMA) homopolymers comprised of highly hydrophobic LMA moieties with -COOH polar end groups were synthesized by employing reversible addition-fragmentation chain transfer (RAFT) polymerization. Ethylene glycol dimethacrylate (EGDMA) was utilized as the branching agent. End groups are incorporated through the RAFT agent utilized. The resulting amphiphilic hyperbranched polymer was molecularly characterized by size exclusion chromatography (SEC), Fourier transformation infrared spectroscopy (FT-IR), and 1H-NMR spectroscopy. Pyrene, curcumin, and IR-1048 dye were hydrophobic payload molecules successfully encapsulated to show how adaptable these homopolymer nanoparticles (prepared by nanoprecipitation in water) are as dye nanocarriers. This study demonstrates a simple way of producing excipients by generating polymeric nanoparticles from an amphiphilic, hyperbranched, hydrophobic homopolymer, with a low fraction of polar end groups, for bioimaging purposes.
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  • 文章类型: Journal Article
    在人体中,羧酸酯酶(CEs)在外源性生物代谢和脂质稳态中起着至关重要的作用。但CEs的异常表达与某些疾病高度相关,如高脂血症,糖尿病,还有肝癌.因此,开发一种有效的工具来准确检测活生物体中的CEs具有重要意义。在这里,一种创新的近红外(NIR)荧光探针,TTAP-AB,设计用于基于聚集诱导发射(AIE)机制的CE检测。该探头显示出快速响应(2分钟),出色的灵敏度(检测限=8.14×10-6U/mL),和对CE的高选择性。此外,由于其良好的生物相容性,TTAP-AB探针能够监测药物诱导的活细胞和斑马鱼中CE水平的动态变化。更重要的是,TTAP-AB探针成功地用于成像肝肿瘤,并通过实时监测CEs协助肿瘤切除,表明TTAP-AB有望指导肝癌手术。因此,TTAP-AB探针不仅可以丰富生物系统中的CE检测策略,而且在某些临床成像应用中具有巨大的潜力,包括医学诊断,临床前研究,和影像引导手术。
    In the human body, carboxylesterases (CEs) play crucial roles in xenobiotic metabolism and lipid homeostasis. But abnormal expression of CEs is highly associated with some diseases, such as hyperlipidemia, diabetes, and liver cancer. Therefore, it is of great importance to develop an efficient tool for the accurate detection of CEs in living organisms. Herein, an innovative near-infrared (NIR) fluorescent probe, TTAP-AB, was designed for CE detection based on the aggregation-induced emission (AIE) mechanism. This probe exhibits rapid response (2 min), excellent sensitivity (limit of detection = 8.14 × 10-6 U/mL), and high selectivity to CEs. Additionally, owing to its good biocompatibility, the TTAP-AB probe enables the monitoring of dynamic changes in CE levels under drug-induced modulation in living cells and zebrafish. More importantly, the TTAP-AB probe was successfully employed to image liver tumors and assist in tumor resection through the real-time monitoring of CEs, indicating that TTAP-AB is promising to guide liver cancer surgery. Therefore, the TTAP-AB probe can not only enrich the strategies for CE detection in biological systems but also has great potential for some clinical imaging applications, including medical diagnosis, preclinical research, and imaging-guided surgery.
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  • 文章类型: Journal Article
    荧光寿命成像显微镜(FLIM)是一种强大的成像工具,通过测量荧光衰减时间,提供对样品的分子特异性见解,在不同的研究领域具有广阔的应用前景。然而,为了获取二维寿命图像,传统的FLIM依赖于空间和时间域的广泛扫描,与基于强度的方法相比,导致采集速率慢得多。这个问题在三维成像中被进一步放大,因为它需要沿深度轴进行额外的扫描。最近的进步旨在提高FLIM的速度和三维成像能力。这篇综述探讨了在应对这些挑战方面取得的进展,并讨论了FLIM仪器未来发展的潜在方向。
    Fluorescence lifetime imaging microscopy (FLIM) is a powerful imaging tool offering molecular specific insights into samples through the measurement of fluorescence decay time, with promising applications in diverse research fields. However, to acquire two-dimensional lifetime images, conventional FLIM relies on extensive scanning in both the spatial and temporal domain, resulting in much slower acquisition rates compared to intensity-based approaches. This problem is further magnified in three-dimensional imaging, as it necessitates additional scanning along the depth axis. Recent advancements have aimed to enhance the speed and three-dimensional imaging capabilities of FLIM. This review explores the progress made in addressing these challenges and discusses potential directions for future developments in FLIM instrumentation.
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  • 文章类型: Journal Article
    生物发光,由生物有机体中涉及荧光素酶的生化反应产生的光,已广泛研究各种应用。由于其安全和有效的特性克服了常规外部光源的有限穿透,因此作为用于医疗应用的内部光源引起了特别的兴趣。蛋白质工程技术和蛋白质递送平台的最新进展已将生物发光的应用扩展到广泛的治疗领域,包括生物成像,生物传感,光动力疗法,和光遗传学。这篇全面的综述介绍了生物发光的基本概念,并探讨了其在各个领域的最新应用。此外,它根据生物发光系统的现状讨论了未来的研究方向,以进一步扩大其潜力。
    Bioluminescence, the light produced by biochemical reactions involving luciferases in living organisms, has been extensively investigated for various applications. It has attracted particular interest as an internal light source for theranostic applications due to its safe and efficient characteristics that overcome the limited penetration of conventional external light sources. Recent advancements in protein engineering technologies and protein delivery platforms have expanded the application of bioluminescence to a wide range of theranostic areas, including bioimaging, biosensing, photodynamic therapy, and optogenetics. This comprehensive review presents the fundamental concepts of bioluminescence and explores its recent applications across diverse fields. Moreover, it discusses future research directions based on the current status of bioluminescent systems for further expansion of their potential.
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  • 文章类型: Journal Article
    椎间盘退变是一种主要影响椎间盘的病理生理状况,导致背痛和神经功能缺损.它是由遗传易感性等几个因素的贡献引起的,与年龄有关的变性,以及肥胖和体育锻炼等生活方式的选择。即使有治疗疼痛的药物,缺乏完全治愈的药物。主要困难在于对椎间盘形态和功能变化的诊断不良。随着生物成像技术研究的不断深入,正在开发新技术,并重新用于评估椎间盘的形状和组成,以及它们的缺陷,如椎间盘变薄或畸形,导致椎间盘退变的正确诊断干预。在这次审查中,我们旨在对临床前和临床阶段用于椎间盘退变诊断的影像学技术进行全面概述。首先,我们将讨论关于病理解剖和病理生理学的退行性椎间盘疾病的意义和简要描述各种染料和示踪剂用于生物成像。然后,我们将阐明椎间盘退变诊断方式的最新进展;通过分析用于确定椎间盘退变机制和开发治疗策略的方法和实验系统的影响来总结。
    Intervertebral Disc Degeneration is a pathophysiological condition that primarily affects the spinal discs, causing back pain and neurological deficits. It is caused by the contribution of several factors such as genetic predisposition, age-related degeneration, and lifestyle choices like obesity and physical activity. Even though there are medications to treat pain, there is a lack of medicines for a complete cure. The main difficulty lies in poor diagnosis of the morphological and functional changes in the disc. With the ever-increasing research on bioimaging techniques, new techniques are being developed and repurposed to evaluate disc shape and composition, and their defects like thinning or deformities on the disc, leading to the proper diagnostic intervention in intervertebral disc degeneration. In this review, we aim to present a comprehensive overview of the imaging techniques used in the pre-clinical and clinical stages for the diagnosis of intervertebral disc degeneration. First, we will discuss about patho-anatomy and the pathophysiology of degenerative disc disease with the significance and a brief description of various dyes and tracers utilized for bioimaging. Then we will shed light on the latest advancements in diagnostic modalities in intervertebral disc degeneration; concluded by an analysis of the repercussions of the methodologies and experimental systems employed in identifying mechanisms and developing therapeutic strategies in intervertebral disc degeneration.
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  • 文章类型: Journal Article
    镧系元素具有独特的光物理特性,包括铕,钕,还有镱,使它们适用于研究生物系统的分子工具。具体来说,它们持久的光致发光,精确的发射光谱,和显著的斯托克斯位移允许实验不能实现有机荧光团或荧光蛋白。此外,这些金属离子的发光共振能量转移和光子上转换的能力进一步扩展了镧系元素探针的潜在应用。在这项研究中,合成了一种新的[Nd(NTA)2·H2O]3-配合物,并使用实用的表征技术如UV-Vis吸收评估了其光学性能,光致发光,和FTIR。发现当样品被357nm波长激发时,它在1076nm处发出强线,半峰全宽(FWHM)为10nm,以前没有记录的现象。在理论方法中利用Judd-Ofelt理论及其强度参数来确定[Nd(NTA)2·H2O]3-络合物的荧光分支比和辐射寿命。然后相应地分析吸收和发光光谱。实验结果验证了所制备样品在生物成像中的潜在应用。
    The distinctive photophysical characteristics possessed by lanthanides, including europium, neodymium, and ytterbium, render them adaptable molecular tools for studying biological systems. Specifically, their enduring photoluminescence, precise emission spectra, and significant Stokes shifts allow for experiments not achievable with organic fluorophores or fluorescent proteins. Moreover, the capacity of these metal ions for luminescence resonance energy transfer and photon upconversion extends the potential applications of lanthanide probes even further. In this research, a new [Nd(NTA)2·H2O]3- complex was synthesized and its optical properties were assessed using practical characterization techniques such as UV-Vis absorption, photoluminescence, and FTIR. It was discovered that when the sample was excited by a 357 nm wavelength, it emitted a strong line at 1076 nm with a full-width at half maximum (FWHM) of 10 nm, a phenomenon not previously documented. The Judd-Ofelt theory and its intensity parameters were utilized in a theoretical approach to determine the fluorescence branching ratio and the radiative lifetime of the [Nd(NTA)2·H2O]3- complex. The absorption and luminescence spectra were then analyzed accordingly. Experimental findings validated the potential applications of the prepared sample in bioimaging.
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  • 文章类型: Journal Article
    次氯酸盐(ClO-)和粘度都影响线粒体的生理状态,它们的异常水平与许多常见疾病密切相关。因此,开发线粒体靶向荧光探针对ClO-和粘度的双重传感至关重要。在这里,我们探索了一种新的荧光探针,XTAP-Bn,它对ClO-和粘度敏感地响应,在558和765nm处发生关断荧光变化,分别。因为发射波长间隙大于200nm,XTAP-Bn可以有效消除ClO-和粘度同时检测过程中的信号串扰。此外,XTAP-Bn有几个优点,包括高选择性,快速反应,良好的水溶性,低细胞毒性,和出色的线粒体靶向能力。更重要的是,XTAP-Bn探针已成功用于监测活细胞和斑马鱼线粒体中ClO-和粘度水平的动态变化。这项研究不仅为识别线粒体功能障碍提供了可靠的工具,而且为线粒体相关疾病的早期诊断提供了潜在的方法。
    Hypochlorite (ClO-) and viscosity both affect the physiological state of mitochondria, and their abnormal levels are closely related to many common diseases. Therefore, it is vitally important to develop mitochondria-targeting fluorescent probes for the dual sensing of ClO- and viscosity. Herein, we have explored a new fluorescent probe, XTAP-Bn, which responds sensitively to ClO- and viscosity with off-on fluorescence changes at 558 and 765 nm, respectively. Because the emission wavelength gap is more than 200 nm, XTAP-Bn can effectively eliminate the signal crosstalk during the simultaneous detection of ClO- and viscosity. In addition, XTAP-Bn has several advantages, including high selectivity, rapid response, good water solubility, low cytotoxicity, and excellent mitochondrial-targeting ability. More importantly, probe XTAP-Bn is successfully employed to monitor the dynamic change in ClO- and viscosity levels in the mitochondria of living cells and zebrafish. This study not only provides a reliable tool for identifying mitochondrial dysfunction but also offers a potential approach for the early diagnosis of mitochondrial-related diseases.
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  • 文章类型: Journal Article
    在时空组织的背景下理解组织微环境(TiME)的分子和物理复杂性仍然是一个持久的挑战。工程和数据科学的最新进展现在有望研究结构,功能,和TiME的动态以前所未有的细节;然而,许多进步仍然发生在筒仓中,这些筒仓很少整合信息来研究TiME的全部细节。这篇综述提供了化学基础工程原理的综合概述,光学,电气,机械,和计算科学来探索,感觉,模型,制造TiME。在个别章节中,我们首先总结了基本原理,能力,以及新兴技术的范围,每种技术和最近的突破性发现,有前途的创新。我们提供了这些进步在回答有关TiME及其在各种疾病和发育过程中的作用的关键问题方面的潜力的观点。最后,我们提出了一种综合观点,赞赏TiME研究中的主要科学和教育方面。
    Understanding the molecular and physical complexity of the tissue microenvironment (TiME) in the context of its spatiotemporal organization has remained an enduring challenge. Recent advances in engineering and data science are now promising the ability to study the structure, functions, and dynamics of the TiME in unprecedented detail; however, many advances still occur in silos that rarely integrate information to study the TiME in its full detail. This review provides an integrative overview of the engineering principles underlying chemical, optical, electrical, mechanical, and computational science to probe, sense, model, and fabricate the TiME. In individual sections, we first summarize the underlying principles, capabilities, and scope of emerging technologies, the breakthrough discoveries enabled by each technology and recent, promising innovations. We provide perspectives on the potential of these advances in answering critical questions about the TiME and its role in various disease and developmental processes. Finally, we present an integrative view that appreciates the major scientific and educational aspects in the study of the TiME.
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  • 文章类型: Journal Article
    碳点(CD)已成为一种通用且有前途的碳基纳米材料,具有出色的光学性能,包括可调发射波长,高量子产率,和光稳定性。CD适用于各种应用,有很多好处,如生物相容性,低毒性,和简单的表面改性。由于其可调的光学特性和出色的灵敏度,CD作为荧光探针用于检测pH值,重金属离子,和其他分析物。此外,CD由于其优异的光学质量和不依赖激子的发射,已显示出作为白色有机发光二极管和光发射器在光电子器件中的发光转换器的潜力。由于其生物相容性,CD已用于生物医学领域的药物管理和生物成像,低细胞毒性,和易于功能化。此外,由于其稳定性,高效的电荷分离,低重组率,CD在能源系统中显示出有趣的用途,如光催化和能量转换。本文重点介绍了CD作为与传感和成像相关的各种跨学科领域中适应性纳米材料的不断增长的可能性和潜力,同时解决当前研究中涉及的主要挑战,并提出将CD应用于超级智能社会发展的科学解决方案。
    Carbon dots (CDs) have emerged as a versatile and promising carbon-based nanomaterial with exceptional optical properties, including tunable emission wavelengths, high quantum yield, and photostability. CDs are appropriate for various applications with many benefits, such as biocompatibility, low toxicity, and simplicity of surface modification. Thanks to their tunable optical properties and great sensitivity, CDs have been used in sensing as fluorescent probes for detecting pH, heavy metal ions, and other analytes. In addition, CDs have demonstrated potential as luminescence converters for white organic light-emitting diodes and light emitters in optoelectronic devices due to their superior optical qualities and exciton-independent emission. CDs have been used for drug administration and bioimaging in the biomedical field due to their biocompatibility, low cytotoxicity, and ease of functionalization. Additionally, due to their stability, efficient charge separation, and low recombination rate, CDs have shown interesting uses in energy systems, such as photocatalysis and energy conversion. This article highlights the growing possibilities and potential of CDs as adaptable nanomaterials in a variety of interdisciplinary areas related to sensing and imaging, at the same time addressing the major challenges involved in the current research and proposing scientific solutions to apply CDs in the development of a super smart society.
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  • 文章类型: Journal Article
    铜作为参与细胞增殖和代谢的酶的金属活性位点辅因子和金属结构信号起着关键作用。使其成为癌症治疗的有吸引力的目标。在这项研究中,我们研究了聚多巴胺纳米粒子(PDANP)的功效,经典适用于从水中去除金属,作为在三阴性乳腺癌模型中通过PDA表面存在的金属螯合基团消耗细胞内不稳定铜库的治疗策略。通过使用基于活性的传感探针FCP-1,我们可以跟踪PDA诱导的不稳定铜消耗,同时保持总铜水平不变,并将其与选择性MDA-MB-231细胞死亡联系起来。进一步的机理研究表明,PDANP增加了活性氧(ROS)水平,可能通过超氧化物歧化酶1(SOD1)的失活,一种依赖铜的抗氧化酶.此外,发现PDANP与线粒体膜相互作用,导致线粒体膜电位增加,这可能有助于提高ROS的产量。我们采用体内肿瘤模型来验证PDANP的治疗效果。值得注意的是,在没有任何额外治疗的情况下,在肿瘤生长22天后,单独存在PDANP导致肿瘤体积显著减少1.66倍.我们的发现强调了PDANP作为一种有前途的治疗方法,通过调节铜水平和诱导氧化应激来选择性靶向癌症的潜力。导致肿瘤生长抑制,如这些三阴性乳腺癌模型所示。
    Copper plays critical roles as a metal active site cofactor and metalloallosteric signal for enzymes involved in cell proliferation and metabolism, making it an attractive target for cancer therapy. In this study, we investigated the efficacy of polydopamine nanoparticles (PDA NPs), classically applied for metal removal from water, as a therapeutic strategy for depleting intracellular labile copper pools in triple-negative breast cancer models through the metal-chelating groups present on the PDA surface. By using the activity-based sensing probe FCP-1, we could track the PDA-induced labile copper depletion while leaving total copper levels unchanged and link it to the selective MDA-MB-231 cell death. Further mechanistic investigations revealed that PDA NPs increased reactive oxygen species (ROS) levels, potentially through the inactivation of superoxide dismutase 1 (SOD1), a copper-dependent antioxidant enzyme. Additionally, PDA NPs were found to interact with the mitochondrial membrane, resulting in an increase in the mitochondrial membrane potential, which may contribute to enhanced ROS production. We employed an in vivo tumor model to validate the therapeutic efficacy of PDA NPs. Remarkably, in the absence of any additional treatment, the presence of PDA NPs alone led to a significant reduction in tumor volume by a factor of 1.66 after 22 days of tumor growth. Our findings highlight the potential of PDA NPs as a promising therapeutic approach for selectively targeting cancer by modulating copper levels and inducing oxidative stress, leading to tumor growth inhibition as shown in these triple-negative breast cancer models.
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