适配体在癌症诊断与靶向治疗中的研究进展

核酸适配体是利用体外筛选技术,即指数富集的配体系统进化技术(SELEX),从核酸分子文库中得到的寡核苷酸片段。其与靶标物有很高的特异性和亲和力,将适配体作为识别单元的生物传感研究以及适配体偶联成像试剂的生物体内外成像研究在临床诊断中有很大的应用前景,此外,适配体靶向癌细胞或组织的治疗方法相比传统化学治疗副作用更小,在临床上也有极大的应用前景。本文综述了适配体目前在癌症诊断和靶向治疗两个方面的研究进展,并分析现阶段存在的问题以及面临的挑战。     

Optimized Fluorescent Probe for Specific Imaging of Glutathione S‐Transferases in Living Cells and Mice

GSTP1 has been considered to be a marker for malignancy in many tissues. However, the existing GST fluorescent probes are unfavorable for in vivo imaging because of the limited emission wavelength or insufficient fluorescence enhancement (six‐fold). The limited fluorescence enhancement of GST fluorescent probes is mainly ascribed to the high background signals resulting from the spontaneous reaction between GSH and the probes. In this work, a highly specific GST probe with NIR emission has been successfully developed through optimization of the essential unit of the probe to repress the spontaneous reaction. The novel GST probe exhibits over 100‐fold fluorescence enhancement upon incubation with GSTP1/GSH and high selectivity over other potential interference. In addition, the probe has been proved to be capable of tracking endogenous GST in A549 cells. Finally, the in vivo imaging results demonstrate that the probe can be used for effective imaging of endogenous GST activity in subcutaneous tumor mouse with high contrast.     

Hahn-echoes from N in solids by the stray-field method: prospects for imaging using Long Echo-Train Summation

We have observed Hahn-echoes resulting from Powles–Mansfield pulse-sequences for a variety of nitrogen containing solids which exhibit a range of ¹⁴N electric quadrupole coupling constants (C_q) from 0 to 4.9 MHz. Long echo-decays were frequently obtained which allowed the collection of many echoes in one echo-train, so that the method of Long Echo-Train Summation (LETS), could be used to accumulate signal. A one-dimensional STRAFI-profile is shown for solid ammonium nitrate. The spatial resolution is discussed as a function of C_q.     

Design, synthesis, and biological evaluation of a dansyled amino acid derivative as an imaging agent for apoptosis

To develop a small molecule-based biomarker for in vivo apoptosis imaging, a dansyled amino acid derivative (BNSBA) was designed and synthesized in good yield. The biological evaluation demonstrated that BNSBA selectively binds to apoptotic cancer cells and is localized within the cytoplasm of cells that bound annexin V on the plasma membrane.     

Multiplex chemiluminescence microscope imaging of P16INK4A and HPV DNA as biomarker of cervical neoplasia

Classification of cervical intraepithelial neoplasia (CIN) lesions in low-grade (CIN1) or high-grade (CIN2-3) ones is crucial for optimal patient management, but current histological diagnosis on bioptic samples is often hampered by inter-observer variability. To allow objective classification, we have exploited the peculiar characteristics of chemiluminescence detection, such as high sensitivity and easy quantification of the luminescence signal, to perform sequentially in the same tissue section both an immunohistochemical quantitative detection of p16^INK4A (a protein marker of high-grade CIN lesions) and an in situ hybridization for human papillomavirus (generally accepted as a necessary but insufficient cause of cervical carcinoma). Different label enzymes (alkaline phosphatase and horseradish peroxidase) were employed in order to avoid any interference between the two assays, and quantitative chemiluminescence image analysis was used to obtain objective evaluation of sample positivity. The multiplexed method allowed detection of two complementary biomarkers and provided discrimination between different lesions (non-neoplastic, low-grade and high-grade CIN). This assay might thus represent an accurate and objective diagnostic test providing important information for counseling, selection of therapy and follow up after surgical treatment.     

红外图像法鉴别打印机种类

采用红外图像系统对收集到的针式、激光、喷墨3种类型打印机的打印字迹样本各4份分别进行检验,依据3类打印机打印字迹的可见图像、化学图像和红外谱图,可以鉴别3种类型的打印机。可见图像鉴别可根据字迹的清晰程度及有无虚边等特点加以鉴别,化学图像鉴别可根据在不同的波程范围上化学图像清晰程度不同为依据。红外谱图部分主要是在相同的波程上吸收峰数目不同作为鉴别的主要依据。通过红外图像法鉴别打印机种类与其他方法相比,具有不破坏检材、检测范围广、检测速度快等优点。     

红外探测器成像实验研究

红外探测器广泛应用于多光谱成像系统中,文章提出并建立了一种红外线阵时间延迟积分探测器的成像实验系统,阐述了成像系统的工作原理,对影响成像质量的两个主要因素电子稳像与自动对焦进行了深入分析。利用高精度直流测速机确定了转台转速与探测器的行转移频率,采用卡尔曼滤波算法滤除了测速机带来的噪声,提高了速度匹配精度。在分析比较红外相机四种检焦方法的基础上采用视频信号幅度法进行检调焦。在国家光学机械产品质量监督检验测试中心实地搭建了成像实验系统,并分别对5.3,6.4和9.2mm宽度靶标成像。实验结果表明,采集到的原始靶标纹理清晰,照相分辨率达到了每毫米11.3对线,达到了实验预期目的。     

Direct Visualization of Nanoconfinement Effect on Nanoreactor via Electrochemiluminescence Microscopy

Nanoconfinement in mesoporous nanoarchitectures could dramatically change molecular transport and reaction kinetics during electrochemical process. A molecular-level understanding of nanoconfinement and mass transport is critical for the applications, but a proper route to study it is lacking. Herein, we develop a single nanoreactor electrochemiluminescence (SNECL) microscopy based on Ru(bpy)₃²⁺-loaded mesoporous silica nanoparticle to directly visualize in situ nanoconfinement-enhanced electrochemical reactions at the single molecule level. Meanwhile, mass transport capability of single nanoreactor, reflected as long decay time and recovery ability, is monitored and simulated with a high spatial resolution. The nanoconfinement effects in our system also enable imaging single proteins on cellular membrane. Our SNECL approach may pave the way to decipher the nanoconfinement effects during electrochemical process, and build bridges between mesoporous nanoarchitectures and potential electrochemical applications.