金纳米棒的表面修饰及其应用于肿瘤诊疗的研究进展

金纳米棒具有独特的光学性质、表面易修饰性、较低的生物毒性和良好的生物相容性,因而在成像、光热治疗和药物载带等方面具有极高的潜在应用价值.本文综述了典型的金纳米棒表面修饰方法及其在生物成像、光热治疗和药物治疗中的应用,重点阐述了通过金纳米棒同时实现肿瘤诊断和治疗相结合的研究进展.     

功能化量子点在肿瘤诊治中的应用

量子点是一种半导体纳米晶体,它可发出激发荧光,具有亮度高、稳定时间长和发射光谱可调节等特性,是同时检测多信号的良好材料.这些独特性质使得它们在肿瘤诊治领域中的应用日益受到人们的重视.对量子点进行功能化修饰,如偶联抗体等活性物质后,可以对肿瘤细胞进行特异性识别及示踪,以实现对肿瘤的诊断和治疗.文中分别从分子靶向识别、淋巴结定位和药物传递等方面探讨了功能化量子点在肿瘤诊断和治疗中的最新进展.此外,还讨论了量子点的毒性以及用于肿瘤检测和治疗的多功能量子点的设计方法,并提出了其实际应用的潜在方向.     

量子点光学成像技术在肿瘤诊断和治疗的应用

纳米技术在生物医学的进展使其在肿瘤的诊治中应用日益广泛。荧光纳米粒子中的量子点(Quantum Dots),具备光学成像特性在肿瘤中应用中显示出独特的优势。其作为一种荧光半导体纳米粒子,具有荧光强度高、稳定性强、激发波谱宽、发射波谱窄等光学特性。同时,它可以结合其他功能基团,包括靶向模式、治疗因素和成像探针,为临床肿瘤诊断和治疗提供了新的潜力。本文就量子点的类型和特点及量子点的肿瘤体外和体内成像进行综述。     

自发光学信号成像系统在生物成像中的发展与应用

自发光学信号成像系统是近年来比较新颖的一项用于活体生物的基因或细胞活动的微观检测的光学技术,具有直观、操作简便以及分辨率高的特点。该技术主要分为生物发光成像技术和荧光成像技术,目前主要用于测定活体动物体内的细胞以及分子的活动或变化情况。由于该技术能够对动物体内的微观形态的变化进行精确的捕捉,对于癌症、基因表达、肿瘤以及其他病变均具有较好的监测作用。在本文中,将就自发光学信号成像系统在生物成像中的发展与应用进行详细的阐述。     

量子点荧光探针在生物成像中的应用进展

量子点荧光探针是近几年发展起来的一种新型荧光标记物,拥有荧光染料及荧光蛋白所不能比拟的独特优势,已经在细胞功能研究及细胞表面和内部功能分子的探测、组织的成像和病灶的定位等方面得到了较为广泛的应用。本文对量子点的光学特性、生物化修饰及其在生物成像等方面的应用进展进行了较为详细的介绍,并展望了其应用发展。     

基于表面修饰的活体细菌药物及递送策略

活体细菌在多种疾病防治领域显示出巨大的应用前景。然而，以细菌为基础的“活体材料”在生物医药应用中普遍面临生物利用度低、作用缺乏靶向性、治疗效果不佳和安全性等问题。表面工程技术为克服上述问题，发展新型活体细菌药物及其先进递送平台提供了重要的手段。该文首先介绍了活体细菌表面修饰的物理和化学手段；进一步讨论了表面修饰后的活体细菌药物所具有的不良环境耐受性、特定作用位点靶向性和定向运动等优良特性；最后总结了表面修饰改造的活体细菌在肿瘤和肠炎等不同疾病的诊断、成像和治疗中的应用。这项工作将有助于推进细菌疗法和活体细菌药物的进一步发展与应用。     

生物正交化学在活体标记及药物传递中的研究进展

生物正交化学反应是一类可以在生理条件下发生的化学反应,具有简单、高效、高特异性的特点,在生物医学的研究中被广泛应用.基于生物体天然生命过程的代谢工程,可对生物分子进行无损、高效的生物代谢修饰,是一种理想的生物修饰技术.通过生物代谢途径可有效地将各种化学报告基团引入靶标物的生物分子中,有利于携带配对基团的标记物与其发生生物正交反应,从而在活体系统中实现生物分子的标记示踪和药物递送.这种基于代谢工程与生物正交化学的标记策略因为具有两者之间的优势,在生物医学工程中的标记、成像示踪、诊断等领域展现出巨大的研究价值与应用潜力.本文介绍了生物正交和代谢工程的原理与生物医学研究进展,阐述了生物正交化学在分子成像和药物传递等方面的研究与应用.     

光学成像在肿瘤研究中的应用

随着分子标记技术的发展,光学成像技术作为一种非侵入性动态成像技术,以其高分辨率、高灵敏度正越来越多的应用于医学和生物学的研究.该文重点介绍了在体生物光学成像技术在肿瘤的转移机制、药物对肿瘤的疗效、肿瘤细胞凋亡、肿瘤血管生成等方面的应用.     

量子点的荧光特性在生物标记成像中的应用及展望

与传统的荧光染料相比,量子点作为一种新型的无机荧光纳米材料,具有激发光谱宽而连续、发射光谱窄而对称、光稳定性好、荧光寿命长、量子产率高和生物毒性小等优点,被广泛地应用于生命科学的许多领域,其在细胞标记(固定细胞和离体活细胞)和活体示踪成像领域具有独特的应用优势.它突破了传统的有机荧光染料在荧光性能及生物毒性等方面的不可克服的缺陷.它的应用,极大地推动了生命体系高灵敏、原位、实时、动态示踪成像研究的发展.该文综述了量子点的荧光性质及其在细胞标记(固定细胞和离体活细胞)和活体实时动态示踪成像中的应用,并对其在荧光原位杂交,流式细胞术,实时荧光定量pcr等方面的应用前景进行了展望.     

碳量子点抗菌活性的研究进展

碳量子点(Carbon quantum dots,CQDs)是一种新型碳纳米材料,具有独特的性质,逐渐得到广泛关注。由于CQDs主要是通过"自下而上"的方法制备,其表面具有更加丰富多样的基团,因此更容易衍生化和功能化,进而更容易得到具有特殊性质和功能的CQDs。同时,CQDs在水溶性、可修饰性、耐光漂白等方面具有明显的优势,并且还兼具低生物毒性和良好的生物相容性,使其在生物成像、生物传感和生物分子/药物传递等方面具有潜在的应用价值。随着CQDs研究的增多,各种不同功能化的CQDs得到发展,并被越来越多地用于抗菌方面。根据CQDs目前在医学领域的发展,本文对CQDs在抗菌方面的最新研究进展作一综述。     

Characterization of VCAM-1-Binding Peptide-Functionalized Quantum Dots for Molecular Imaging of Inflamed Endothelium

Inflammation-induced activation of endothelium constitutes one of the earliest changes during atherogenesis. New imaging techniques that allow detecting activated endothelial cells can improve the identification of persons at high cardiovascular risk in early stages. Quantum dots (QDs) have attractive optical properties such as bright fluorescence and high photostability, and have been increasingly studied and developed for bio-imaging and bio-targeting applications. We report here the development of vascular cell adhesion molecule-1 binding peptide (VCAM-1 binding peptide) functionalized QDs (VQDs) from amino QDs. It was found that the QD fluorescence signal in tumor necrosis factor (TNF-) treated endothelial cells in vitro was significantly higher when these cells were labeled with VQDs than amino QDs. The VQD labeling of TNF--treated endothelial cells was VCAM-1 specific since pre-incubation with recombinant VCAM-1 blocked cells'' uptake of VQDs. Our ex vivo and in vivo experiments showed that in the inflamed endothelium, QD fluorescence signal from VQDs was also much stronger than that of amino QDs. Moreover, we observed that the QD fluorescence peak was significantly blue-shifted after VQDs interacted with aortic endothelial cells in vivo and in vitro. A similar blue-shift was observed after VQDs were incubated with recombinant VCAM-1 in tube. We anticipate that the specific interaction between VQDs and VCAM-1 and the blue-shift of the QD fluorescence peak can be very useful for VCAM-1 detection in vivo.     

基于受激发射损耗显微术的活细胞和活体超分辨成像

细胞作为生命体基本的结构和功能单元，在生物、医学等领域有着非常重要的研究意义。随着现代科学和技术的发展，科学家们借助电镜对细胞以及细胞器的空间结构已经有非常清晰的认识，但是对它们的功能以及细胞之间的相互作用却了解得非常少，而这恰恰又是疾病治疗和药物开发亟需了解的信息，因此对离体活细胞（简称活细胞）和活体生物组织细胞（简称活体细胞）中亚细胞器的研究变得非常重要。然而细胞中许多细胞器的结构在纳米量级，传统的光学成像技术由于受到光学衍射极限的限制是无法观察到纳米量级的生物结构，因此光学超分辨成像技术是目前研究亚细胞器结构和功能的有效工具。在所有光学超分辨显微技术中，受激发射损耗显微术（stimulated emission depletionmicroscopy,STED）由于具有实时成像、三维超分辨和断层成像的能力，非常适合用于纳米尺度的活细胞和活体细胞成像研究，而且STED超分辨成像技术经过近几十年的发展，已经广泛用于活细胞甚至活体小鼠细胞的超分辨动态观测。本文总结了近年来活细胞和活体小鼠神经元细胞等领域STED超分辨成像的研究进展，介绍了用于活细胞和活体细胞STED超分辨成像的荧光染料...     

Bioconjugated quantum dots for cancer research: Present status,prospects and remaining issues

Semiconductor quantum dots (QDs) are nanoparticles in which charge carriers are three dimensionally confined or quantum confined. The quantum confinement provides size-tunable absorption bands and emission color to QDs. Also, the photoluminescence (PL) of QDs is exceptionally bright and stable, making them potential candidates for biomedical imaging and therapeutic interventions. Although fluorescence imaging and photodynamic therapy (PDT) of cancer have many advantages over imaging using ionizing radiations and chemo and radiation therapies, advancement of PDT is limited due to the poor availability of photostable and NIR fluorophores and photosensitizing (PS) drugs. With the introduction of biocompatible and NIR QDs, fluorescence imaging and PDT of cancer have received new dimensions and drive. In this review, we summarize the prospects of QDs for imaging and PDT of cancer. Specifically, synthesis of visible and NIR QDs, targeting cancer cells with QDs, in vitro and in vivo cancer imaging, multimodality, preparation of QD-PS conjugates and their energy transfer, photosensitized production of reactive oxygen intermediates (ROI), and the prospects and remaining issues in the advancement of QD probes for imaging and PDT of cancer are summarized.     

Cadmium-containing quantum dots: properties,applications, and toxicity

The marriage of biology with nanomaterials has significantly accelerated advancement of biological techniques, profoundly facilitating practical applications in biomedical fields. With unique optical properties (e.g., tunable broad excitation, narrow emission spectra, robust photostability, and high quantum yield), fluorescent quantum dots (QDs) have been reasonably functionalized with controllable interfaces and extensively used as a new class of optical probe in biological researches. In this review, we summarize the recent progress in synthesis and properties of QDs. Moreover, we provide an overview of the outstanding potential of QDs for biomedical research and innovative methods of drug delivery. Specifically, the applications of QDs as novel fluorescent nanomaterials for biomedical sensing and imaging have been detailedly highlighted and discussed. In addition, recent concerns on potential toxicity of QDs are also introduced, ranging from cell researches to animal models.

     

In‐vivo Tumor detection using diffusion reflection measurements of targeted gold nanorods – a quantitative study

The ability to quantitatively and non‐invasively detect nanoparticles has important implications on their development as an in‐vivo cancer diagnostic tool. The Diffusion Reflection (DR) method is a simple, non‐invasive imaging technique which has been proven useful for the investigation of tissue's optical parameters. In this study, Monte Carlo (MC) simulations, tissue‐like phantom experiments and in‐vivo measurements of the reflected light intensity from tumor bearing mice are presented. Following intravenous injection of antibody conjugated poly (ethylene glycol)‐coated (PEGylated) gold nanorods (GNR) to tumor‐bearing mice, accumulation of GNR in the tumor was clearly detected by the DR profile of the tumor. The ability of DR measurements to quantitate in‐vivo the concentration of the GNR in the tumor was demonstrated and validated with Flame Atomic Absorption spectroscopy results. With GNR as absorbing contrast agents, DR has important potential applications in the image guided therapy of superficial tumors such as head and neck cancer, breast cancer and melanoma. (© 2012 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

Acetazolamide-based [18F]-PET tracer: In vivo validation of carbonic anhydrase IX as a sole target for imaging of CA-IX expressing hypoxic solid tumors

Carbonic anhydrase IX is overexpressed in many solid tumors including hypoxic tumors and is a potential target for cancer therapy and diagnosis. Reported imaging agents targeting CA-IX are successful mostly in clear cell renal carcinoma as SKRC-52 and no candidate was approved yet in clinical trials for imaging of CA-IX. To validate CA-IX as a valid target for imaging of hypoxic tumor, we designed and synthesized novel [¹⁸F]-PET tracer (1) based on acetazolamide which is one of the well-known CA-IX inhibitors and performed imaging study in CA-IX expressing hypoxic tumor model as 4T1 and HT-29 in vivo models other than SKRC-52. [¹⁸F]-acetazolamide (1) was found to be insufficient for the specific accumulation in CA-IX expressing tumor. This study might be useful to understand in vivo behavior of acetazolamide PET tracer and can contribute to the development of successful PET imaging agents targeting CA-IX in future. Additional study is needed to understand the mechanism of poor targeting of CA-IX, as if CA-IX is not reliable as a sole target for imaging of CA-IX expressing hypoxic solid tumors.     

Fluorescence intensity modulation of CdSe/ZnS quantum dots assesses reactive oxygen species during chemotherapy and radiotherapy for cancer cells

Quantum dots (QDs) are semiconductor nanoparticles ranging in size from 2 to 10 nm. QDs are increasingly being developed for biomedical imaging, targeted drug delivery and green energy technology. These have led to much research on QD interactions with various physical, chemical and biological systems. For biological systems, research has focused on the biocompatibility/cytotoxicity of QDs in the context of imaging/therapy. However, there is a paucity of work on how biological systems and bioactive molecules might be used to alter the optoelectronic properties of QDs. Here, it is shown that these properties can be altered by reactive oxygen species (ROS) from chemotherapeutic media and biological cells following controlled changes in cellular activities. Using CdSe/ZnS core‐shell QDs, spectroscopic analysis of optically excited QDs with HL60, K562 and T98G cancer cell lines is performed. Our results show statistically significant (P < 0.0001) modulation of the fluorescence emission spectra of the QDs due to the ROS produced by common chemotherapeutic drugs, daunorubicin and doxorubicin and by cells following chemotherapy/radiotherapy. This optical modulation, in addition to assessing ROS generation, will possibly enhance applications of QDs in simultaneous diagnostic imaging and nanoparticle‐mediated drug delivery as well as simultaneous ROS assessment and radiosensitization for improved outcomes in cancer treatments. Reactive molecular species produced by biological cells and chemotherapeutic drugs can create electric fields that alter the photophysical properties of QDs, and this can be used for concurrent monitoring of cellular activities, while inducing changes in those cellular activities.      

Microwave‐assisted aqueous synthesis of new quaternary‐alloyed CdSeTeS quantum dots; and their bioapplications in targeted imaging of cancer cells

In this study, we report for the first time a one‐pot approach for the synthesis of new CdSeTeS quaternary‐alloyed quantum dots (QDs) in aqueous phase by microwave irradiation. CdCl₂ was used as a Cd precursor during synthesis, NaHTe and NaHSe were used as Te and Se precursors and mercaptopropionic acid (MPA) was used as a stabilizer and source of sulfur. A series of quaternary‐alloyed QDs of different sizes were prepared. CdSeTeS QDs exhibited a wide emission range from 549 to 709 nm and high quantum yield (QY) up to 57.7 %. Most importantly, the quaternary‐alloyed QDs possessed significantly long fluorescence lifetimes > 100 ns as well as excellent photostability. Results of high‐resolution transmission electron microscopy (HRTEM), energy dispersive X‐ray spectroscopy (EDX) and powder X‐ray diffraction (XRD) spectroscopy showed that the nanocrystals possessed a quaternary alloy structure with good crystallinity. Fluorescence correlation spectroscopy (FCS) showed that QDs possessed good water solubility and monodispersity in aqueous solution. Furthermore, CdSeTeS QDs were modified with alpha‐thio‐omega‐carboxy poly(ethylene glycol) (HS‐PEG‐COOH) and the modified QDs were linked to anti‐epidermal growth factor receptor (EGFR) antibodies. QDs with the EGFR antibodies as labeling probes were successfully applied to targeted imaging for EGFR on the surface of SiHa cervical cancer cells. We believe that CdSeTeS QDs can become useful probes for in vivo targeted imaging and clinical diagnosis. Copyright © 2012 John Wiley & Sons, Ltd.     

Biokinetics and <Emphasis Type="Italic">In Vivo</Emphasis> Distribution Behaviours of Silica-Coated Cadmium Selenide Quantum Dots

Recently, quantum dots derived from trace elements like cadmium and selenium have attracted widespread interest in biology and medicine. They are rapidly being used as novel tools for both diagnostic and therapeutic purposes. In this report, we evaluated the distribution of silica-coated cadmium selenide (CdSe) quantum dots (QDs) following intravenous injection into male Swiss albino mice as a model system for determining tissue localization using in vivo fluorescence and ex vivo elemental analysis by inductively coupled plasma optical emission spectroscopy (ICP-OES). Trioctylphosphine oxide-capped CdSe quantum dots were synthesized and rendered water soluble by overcoating with silica, using aminopropyl silane (APS) as silica precursor. ICP-OES was used to measure the cadmium content to indicate the concentration of QDs in blood, organs and excretion samples collected at predetermined time intervals. Meanwhile, the distribution and aggregation state of QDs in tissues were also investigated in cryosections of the organs by fluorescence microscopy. We have demonstrated that the liver and kidney were the main target organs for QDs. Our systematic investigation clearly shows that most of the QDs were metabolized in the liver and excreted via faeces and urine in vivo. A fraction of free QDs, maintaining their original form, could be filtered by glomerular capillaries and excreted via urine as small molecules within 5 days.