纳米金刚石材料在生物医药领域中的应用

纳米金刚石是一种具有生物相容性、低毒性、荧光效应等特性的纳米惰性材料,近年来逐步在药物载体材料、生物成像工具、荧光探针材料以及量子探针等生物医药领域突显出其愈来愈重要的作用。本文从蛋白质的分离与纯化、细胞标记与生物成像、基因传输与治疗、对免疫系统的作用、癌症诊断与治疗、药物传输与治疗、生物传感等角度综述了纳米金刚石材料在生物医药领域中的应用现状及主要发展态势,对于将纳米金刚石应用于生物医药领域的学者有重要的参考价值。     

量子点探针辅助的近红外荧光成像技术在肿瘤显影中的应用

肿瘤早期检测是精准并高效诊疗癌症的关键因素。荧光成像技术凭借其高灵敏度、高时空分辨率、无电离辐射和无创实时成像等优点,在生物医学领域,尤其在肿瘤检测方面展现出了广泛的应用前景。近红外光穿过生物组织时,受到的吸收和散射较少,因此在生物成像方面体现了高信噪比和强组织穿透能力。在众多荧光探针中,近红外发光的量子点探针因其量子产率高、抗光漂白性强、发射光可调和稳定性良好等特点在荧光成像方面显示出突出的优势。本文基于量子点探针的近红外荧光成像技术在肿瘤显影中的应用,介绍了量子点优异的光学性能,并重点讨论了硫化铅（PbS）和硫化银（Ag2S）近红外发光量子点探针在肿瘤成像方面的研究进展,并对近红外发光量子点探针的应用前景进行了展望。     

水溶性BODIPY类近红外荧光探针的合成及生物组织成像研究

【摘要】目的长波吸收和发射的水溶性荧光染料被广泛应用于生物技术和生物医学领域,如DNA排序、诊断成像和光动力治疗等。方法为了开发具有近红外荧光特性的分子探针,通过Knoevenagel缩合反应合成一种新型水溶性荧光化合物——荧光染料（BODIPY）;评价了其光学性能,并以裸鼠为实验动物评价了该探针在生物组织成像中的效果。结果这类荧光化合物具有良好的水溶性和光学性能,对正常裸鼠深层组织和脏器具有明显成像效果。结论该类探针在荧光影像学诊断方面具有很好的应用潜力。     

荧光分子成像的探针技术及其应用

近几年,随着生物和基因技术的发展,荧光探针的获取手段越来越丰富.荧光探针的发展使得荧光分子成像技术及其应用备受关注.借助于荧光探针,可以对目标分子、蛋白质、基因等特异性成像,从而实现分子、蛋白、基因等的精确定位与分析,进一步实现疾病的早期诊断与治疗.主要对荧光分子成像技术中用到的荧光探针技术以及在生物医学领域的应用进行概述.     

动态荧光分子成像技术研究进展

动态荧光分子成像技术能够描述荧光分子探针在生物体内吸收、分布以及排出的完整过程,是一种可以对生物体的生理、病理过程进行连续监测的动态成像技术.这项技术具有无电离辐射、成像速度快、灵敏度及特异度高、费用低廉等优点,在基础医学及临床医学研究中具有广阔的应用前景.从系统、算法和应用3个方面对动态荧光分子成像技术的研究进展进行了综述.     

基于聚集诱导发光的多肽荧光探针的制备及其在早期龋齿检测中的应用

目的:制备基于聚集诱导发光的多肽荧光探针,并对其在早期龋齿检测中的应用进行探讨。方法:将8个天冬氨酸-丝氨酸-丝氨酸(DSS)与聚集诱导发光材料结合制备多肽荧光探针,体外建立人工脱矿模型,将样本浸泡于多肽荧光探针溶液中1 min,应用荧光成像系统对牙齿样本进行检测并收集图像和荧光数据。同时应用扫描电镜观察牙齿的表型,电子显微镜检测牙齿釉质表面钙磷比,偏光显微镜观察牙齿釉质区域。结果:多肽荧光探针处理区域明显可以观察到脱矿牙齿的荧光强度低于正常牙齿,且差异有统计学意义( P<0.05)。扫描电镜显示脱矿组的牙釉质表面可见较多不规则孔隙;未脱矿组的牙釉质表面较为表面平坦,可见一些不规则的片状物堆积。偏振光显微镜结果显示正常牙齿的釉质区域可以观察到明显的双折射,而脱矿牙齿的釉质区域可以观察到一道黑色区域,或是双折射效应消失,可见部分黑色暗影。 结论:制备了一种基于聚集诱导发光的多肽荧光探针,其能够精准定位牙釉质,在早期龋齿检测中具有一定的应用价值。     

荧光分子断层成像系统的研究进展与比较

荧光分子断层成像（FMT）利用具有特异性的荧光分子探针,在体成像、观测生物体内细胞和分子水平的变化。介绍FMT系统的国内外研究进展,从系统的复杂性、投影数目、光源-探测器（S-D）数据对集大小、重构图像的质量等方面,分析5种S-D几何结构的特点。着重从实现方面,分析、比较已报道的几种FMT系统的特点,并对其多模态成像的可扩展性、临床应用的可能性等进行了总结与展望。     

量子点在生物成像中的应用与研究进展

纳米材料在分子成像及肿瘤靶向治疗方面的作用越来越被重视,量子点由于具有丰富的表面化学性质和明亮稳定的荧光特性,被作为一种新型的纳米探针广泛地应用于分子、细胞及体内生物成像中.近年来,有关量子点的表面修饰及其在细胞和动物体内的成像方面研究不断深入,就量子点在生物成像中研究与应用的最新进展作一综述.     

近红外二区荧光探针在宫颈癌成像与治疗中的应用

宫颈癌是最常见的妇科恶性肿瘤之一，早期、有效的诊断与治疗对提高患者生存率及生活质量具有重要意义。荧光成像已被广泛应用于癌症的早期检测，但由于光在深层组织内传播时，受穿透深度和散射的影响，不利于实现深层组织高清成像。近红外二区（near-infrared-Ⅱ，NIR-Ⅱ；900～1 700nm）成像技术与近红外一区（near-infrared-Ⅰ，NIR-Ⅰ；760～900 nm）成像技术相比，具备更高的信噪比和对比度、更低的自发荧光和更高的空间分辨率，是当前光学、生物医学等多学科的研究热点，非常适合宫颈癌的高质量荧光成像。高质量的荧光成像需要借助良好的荧光探针来精确定位肿瘤组织及其边界并监测治疗过程。目前已开发了一系列基于有机和无机材料的NIR-Ⅱ荧光探针。本文概述了几种典型的NIR-Ⅱ荧光探针及其辅助的NIR-Ⅱ荧光成像技术在宫颈癌成像及治疗方面的应用。     

非对称酞菁作为荧光探针的研究与展望

酞菁在生物、医疗方面的应用研究越来越受到人们的关注,但这方面的研究大多以对称酞菁为主,本文对非对称酞菁及其衍生物作为荧光探针的设计思路、合成方法及其研究现状加以综述,展望了非对称酞菁用作荧光探针在生物大分子标记方面的应用前景。     

Dual-modal upconversion fluorescent/X-ray imaging using ligand-free hexagonal phase NaLuF4:Gd/Yb/Er nanorods for blood vessel visualization

Visualization of blood vessel of lung can improve the detection of the lung and pulmonary vascular diseases. However, research on visualization of blood vessel of lung using the new generation upconversion nanoprobes is still scarce. Herein, high quality hexagonal phase NaLuF₄:Gd/Yb/Er nanorods were synthesized by a simple hydrothermal method through doping Gd³⁺. Doping Gd can not only promote the phase transformation from cubic to hexagonal and the shape evolution from microtube to rod-like, but also provide an additional magnetic properties for biomedical application. The as-prepared nanorods were further converted to water solubility by treating with HCl for eliminating the capped oleic acid. The ligand-free nanorods were successfully used for high-contrast upconversion fluorescent bioimaging of HeLa cells. Moreover, the in vivo synergistic upconversion fluorescent and X-ray imaging of nude mice were demonstrated by subcutaneously and intravenously administrated the ligand-free nanorods. The X-ray signals were matched well with the upconversion signal, indicating the successfully synergistic bioimaging. The ex-vivo X-ray and upconversion fluorescent imaging of various organs revealed that the nanorods were mainly accumulated in liver and lung. More importantly, the blood vessel of the lung can be readily visualized when these ligand-free nanorods are intravenously injected. Apart from the synergistic X-ray and upconversion bioimaging, the ligand-free nanorods can also possess excellent paramagnetic property for potential magnetic resonance imaging contrast agent. Our results have demonstrated the enhanced visualization of blood vessel of lung performed by dual-modal bioimaging of X-ray and upconversion fluorescence, revealing the great promise of these nanoprobes in angiography imaging. Such a new technique enables the integration of the two bioimaging techniques by combining their collective strengths and minimizing their shortcomings.     

Quantum dots light up pathology

Quantum dots (QDs) are novel nanocrystal fluorophores with extremely high fluorescence efficiency and minimal photobleaching. They also possess a constant excitation wavelength together with sharp and symmetrical tunable emission spectra. These unique optical properties make them near-perfect fluorescent markers and there has recently been rapid development of their use for bioimaging. QDs can be conjugated to a wide range of biological targets, including proteins, antibodies, and nucleic acid probes, rendering them of particular interest to pathology researchers. They have been used in multiplex immunohistochemistry and in situ hybridization, which when combined with multispectral imaging, has enabled quantitative measurement of gene expression in situ. QDs have also been used for live in vivo animal imaging and are now being applied to an ever-increasing range of biological problems. These are detailed in this review, which also acts to outline the important advances that have been made in their range of applications. The relative novelty of QDs can present problems in their practical use and guidelines for their application are given.     

Ultrabright organic dots with aggregation-induced emission characteristics for cell tracking

Noninvasive fluorescence cell tracking provides critical information on the physiological displacement and translocation of actively migrating cells, which deepens our understanding of biomedical engineering, oncological research, stem cell transplantation and therapies. Non-viral fluorescent protein transfection based cell tracing has been widely used but with issues related to cell type-dependent expression, lagged readout, immunogenicity and mutagenesis. Alternative cell tracking methods are therefore desired to attain reliable, stable, and efficient labeling over a long time. In this work, we have successfully developed ultra-bright organic dots with aggregation-induced emission (AIE dots) and demonstrated their capabilities for cellular imaging and cell tracking. The AIE dots possess high fluorescence, super photostability, and excellent cellular retention and biocompatibility. As compared to commonly used pMAX-GFP plasmid labeling approach, the organic AIE dots showed excellent cell labeling on all tested human cell lines and superior tracing performance, which opens up new opportunities in the cell-based immunotherapies and other related biological researches.     

Fluorine-18 labeled rare-earth nanoparticles for positron emission tomography (PET) imaging of sentinel lymph node

Rare-earth-based nanoparticles have attracted increasing attention for their unique optical and magnetic properties. However, their application in bioimaging has been limited to photoluminescence bioimaging and magnetic resonance imaging. To facilitate their use in other bioimaging techniques, we developed a simple, rapid, efficient and general synthesis strategy for (18)F-labeled rare-earth nanoparticles through a facile inorganic reaction between rare-earth cations and fluoride ions. The (18)F-labeling process based on rare-earth elements was achieved efficiently in water at room temperature with an (18)F-labeling yield of >90% and completed within 5 min, with only simple purification by aqueous washing and centrifugation, and without the use of organic agents. The effectiveness of (18)F-labeled rare-earth nanoparticles was further evaluated by positron emission tomography (PET) imaging of their in vivo distribution and application in lymph monitoring. In addition, this strategy is proposed for the creation of a dual-model bioimaging technique, combining upconversion luminescence bioimaging and PET imaging.     

A microwave-assisted solution combustion synthesis to produce europium-doped calcium phosphate nanowhiskers for bioimaging applications

Biocompatible nanoparticles possessing fluorescent properties offer attractive possibilities for multifunctional bioimaging and/or drug and gene delivery applications. Many of the limitations with current imaging systems center on the properties of the optical probes in relation to equipment technical capabilities. Here we introduce a novel high aspect ratio and highly crystalline europium-doped calcium phosphate nanowhisker produced using a simple microwave-assisted solution combustion synthesis method for use as a multifunctional bioimaging probe. X-ray diffraction confirmed the material phase as europium-doped hydroxyapatite. Fluorescence emission and excitation spectra and their corresponding peaks were identified using spectrofluorimetry and validated with fluorescence, confocal and multiphoton microscopy. The nanowhiskers were found to exhibit red and far red wavelength fluorescence under ultraviolet excitation with an optimal peak emission of 696 nm achieved with a 350 nm excitation. Relatively narrow emission bands were observed, which may permit their use in multicolor imaging applications. Confocal and multiphoton microscopy confirmed that the nanoparticles provide sufficient intensity to be utilized in imaging applications.     

Composites with AIEgens for Temperature Sensing and Strain Measurement

Traditional fluorescent molecules are easily quenched in most solid applications. Materials with aggregation‐induced emission (AIE) characteristics offer a new way to solve this problem. In this paper, polymer composites consisting of tetraphenylethene (TPE) with AIE properties and polydimethylsiloxane (PDMS) are developed by a simple blending method. The prepared material shows a variable fluorescent emission with different TPE concentrations in the polymer matrix. Such a unique phenomenon arises mainly from the transition of the AIEgen from the crystal to the amorphous state. Interestingly, the fluorescent emission of composites is strongly affected by external factors, such as temperature and mechanical conditions, thus giving the material a stimuli‐sensitive fluorescence property. Specifically, the fluorescence intensity of composites decreases with an increasing temperature, and the same response exhibits when the mechanical force is applied to the material. The excellent response of composites to the temperature and mechanical deformation guarantees the sensory applications of the developed material.     

活细胞内单分子视踪检测研究进展

对细胞生物学与分子生物学中有关分子事件和相互作用的认识,大部分都是在非活体条件下、忽略分子事件全过程所得到的研究结果,并且这些研究结果是基于被研究的所有单分子在相同的环境以相同的方式运动这个不真实的假设.随着量子点(QDs)等新的荧光物质和抗体模拟物等小分子抗体连接后制备成的新型探针的出现,以及转导外源性荧光探针进入活细胞内的各种方法的发展,再加上优良的荧光成像系统和快速灵敏的荧光采集系统在生命科学中的应用,使得视踪活细胞单个生物分子的轨迹、运动及多种单分子的相互作用成为现实.单分子水平的视踪研究为细胞生物学和分子生物学的研究打开了新的篇章.概述了目前活细胞内单分子视踪技术的研究进展并评价了其发展前景.     

量子点荧光标记应用于生物学的研究进展

量子点标记作为一种新型的荧光标记方法,应用于生物学领域的研究有其不可比拟的优势,短短数年在生物化学、细胞生物学、免疫化学等学科的研究中显示了它的巨大发展潜力。本文就量子点优于传统有机荧光染料的性质、量子点标记近年来在生物领域中的研究进展和应用前景作一阐述。     

Amphiphilic protein micelles for targeted in vivo imaging

A variety of polymeric nanoparticles have been developed for bioimaging applications. This study reports on the use of a 50 nm recombinant protein nanoparticle with a multivalent surface as a vehicle for functionalization with a model imaging agent. Multiple fluorescent probes were covalently conjugated to surface amines of crosslinked amphiphilic elastin-mimetic protein micelles using N-hydroxysuccinimide ester chemistry. In vivo fluorescence imaging confirmed that protein micelles selectively accumulated at sites of angioplasty induced vessel wall injury, presumably via an enhanced permeability and retention effect. This investigation demonstrates the potential of amphiphilic protein micelles to be used as a vehicle for selective imaging of sites associated with a disrupted or leaky endothelium.