Lighting Up the Plasma Membrane: Development and Applications of Fluorescent Ligands for Transmembrane Proteins

Despite the fact that transmembrane proteins represent the main therapeutic targets for decades, complete and in-depth knowledge about their biochemical and pharmacological profiling is not fully available. In this regard, target-tailored small-molecule fluorescent ligands are a viable approach to fill in the missing pieces of the puzzle. Such tools, coupled with the ability of high-precision optical techniques to image with an unprecedented resolution at a single-molecule level, helped unraveling many of the conundrums related to plasma proteins’ life-cycle and druggability. Herein, we review the recent progress made during the last two decades in fluorescent ligand design and potential applications in fluorescence microscopy of voltage-gated ion channels, ligand-gated ion channels and G-coupled protein receptors.     

A Small-Molecule Diketopyrrolopyrrole-Based Dye for in vivo NIR-IIa Fluorescence Bioimaging

Organic small-molecule fluorophores with near-infrared IIa (NIR-IIa) emission have great potential in pre-clinical detection and inoperative imaging due to the high-spatial resolution and deep penetration. However, developments of the NIR-IIa fluorophores are still facing considerable challenges. In this work, a series of diketopyrrolopyrrole (DPP)-based fluorophores were designed and synthesized. Subsequently, nanomaterial T25@F127 with significant NIR-IIa emission properties was rationally prepared by encapsulating DPP-based fluorophore T25 , and was selected for fluorescence angiography and cerebral vascular microscopic imaging with nearly 800 μm penetrating depth and excellent signal-background ratio of 4.07 and 2.26 (at 250 and 400 μm), respectively. Furthermore, the nanomaterial T25@cRGD with tumor targeting ability can image tiny metastatic tumor on intestine with a small size of 0.3 mm×1.0 mm and high-spatial resolution (SBR=3.84). This study demonstrates that the nanomaterials which encapsulated T25 behave as excellent NIR-IIa fluorescence imaging agents and have a great potential for in vivo biological application.     

Facile Synthesis of Manganese Tellurite Nanoparticles for Magnetic Resonance Imaging-Guided Photothermal Therapy

In this study, manganese tellurite (MnTeO₃) nanoparticles are developed as theranostic agents for magnetic resonance imaging (MRI)-guided photothermal therapy of tumor. MnTeO₃ nanoparticles are synthesized via a simple one-step method. The as-synthesized MnTeO₃ nanoparticles with uniform size show good biocompatibility. In particular, MnTeO₃ nanoparticles exhibit a high photothermal conversion efficiency (η = 26.3%), which is higher than that of gold nanorods. Moreover, MnTeO₃ nanoparticles also have high MRI performance. The longitudinal relaxivity (r₁) value of MnTeO₃ nanoparticles is determined to be 8.08 ± 0.2 mm ⁻¹ s⁻¹, which is higher than that of clinically approved T₁-contrast agents Gd-DTPA (4.49 ± 0.1 mm ⁻¹ s⁻¹). The subsequent MnTeO₃ nanoparticles-mediated photothermal therapy displays a highly efficient ablation of tumor cells both in vitro and in vivo with negligible toxicity. It is demonstrated that MnTeO₃ nanoparticles can serve as promising theranostic agents with great potentials for MRI-guided photothermal therapy.     

Tantalum Nitride Nanosheets for Photoacoustic Imaging-Guided Photothermal Cancer Therapy

In this study, the synthesis of TaN nanosheets and their application in theranostic agents is reported. After coating polyethylene glycol (PEG) on the TaN nanosheets, the as-synthesized PEG-modified TaN nanosheets (TaN-PEG) show good stability and biocompatibility. Because of their high absorbance in the near-IR region, TaN-PEG can be utilized as photoacoustic imaging contrast agents for tumor imaging. Moreover, TaN-PEG has significant photothermal conversion performance, exhibiting effective laser-induced tumor ablation capability. The TaN-PEG possessing excellent photoacoustic contrast effect and photothermal properties thus have great promise in theranostic applications, especially imaging-guided cancer treatment.     

Nanomaterials in Cerebrovascular Disease Diagnose and Treatment

Cerebrovascular diseases (CVDs) are among the most serious diseases with high mortality and disability rates. The prevalent diagnosis and treatment methods of CVDs include imaging and interventional therapy. With the development of nanotechnology, large numbers of nanomaterials have been applied to the diagnosis and treatment of CVDs, mainly including carbon nanotubes, quantum dots, fullerenes, and dendrimers. In this review, the applications of nanomaterials in the field of diagnosis and treatment of CVDs, mainly including drug target delivery, imaging, therapy, endovascular treatment, and angiogenesis, are summarized. The applications of nanomaterials in the field of CVD are almost in the laboratory, and more effort is needed for clinical translation. The aim of this review is to provide useful information for future research and equipment development.     

FIBSIMS: A review of secondary ion mass spectrometry for analytical dual beam focussed ion beam instruments

Secondary ion mass spectrometry (SIMS) is a well-known technique for 3D chemical mapping at the nanoscale, with detection sensitivity in the range of ppm or even ppb. Energy dispersive X-ray spectroscopy (EDS) is the standard chemical analysis and imaging technique in modern scanning electron microscopes (SEM), and related dual-beam focussed ion beam (FIBSEM) instruments. Contrary to the use of an electron beam, in the past the ion beam in FIBSEMs has predominantly been used for local milling or deposition of material. Here, we review the emerging FIBSIMS technique which exploits the focused ion beam as an analytical probe, providing the capability to perform secondary ion mass spectrometry measurements on FIBSEM instruments: secondary ions, sputtered by the FIB, are collected and selected according to their mass by a mass spectrometer. In this way a complete 3D chemical analysis with high lateral resolution <?50 nm and a depth resolution <?10 nm is attainable.We first report on the historical developments of both SIMS and FIB techniques and review recent developments in both instruments. We then review the physics of interaction for incident particles using Monte Carlo simulations. Next, the components of modern FIBSIMS instruments, from the primary ion generation in the liquid metal source in the FIB column, the focussing optics, the sputtered ion extraction optics, to the different mass spectrometer types are all detailed. The advantages and disadvantages of parallel and serial mass selection in terms of data acquisition and interpretation are highlighted, while the effects of pressure in the FIBSEM, acceleration voltage, ion take-off angles and charge compensation techniques on the analysis results are then discussed. The capabilities of FIBSIMS in terms of sensitivity, lateral and depth resolution and mass resolution are reviewed. Different data acquisition strategies related to dwell time, binning and beam control strategies as well as roughness and edge effects are discussed. Data analysis routines for mass identification based on isotope ratios and molecular fragments are outlined. Application examples are then presented for the fields of thin films, polycrystalline metals, batteries, cultural heritage materials, isotope labelling, and geological materials. Finally, FIBSIMS is compared to EDS, and the potential of the technique for correlative microscopy with other FIBSEM based imaging techniques is discussed.     

碲锌镉面元辐射探测器堆积载流子屏蔽效应

采用铑(Rh)靶45 kV X射线源进行了碲锌镉(CdZnTe)面元像素阵列探测器成像实验。实验结果表明：在探测距离1 mm,管电压45 kV条件下,管电流增大至20 μA时,辐照中心区域像素单元信号丢失,出现围绕辐照中心区域的边缘高事件计数环形探测图像。随着管电流的增大,无响应像素区域扩大,探测器总体事件计数明显降低。进一步根据泊松方程建立了CdZnTe晶体内部电势分布模型,仿真结果表明：单位面积光子通量为5×105 mm-2·s-1时,由于CdZnTe晶体较低的空穴迁移率,晶体内部存在堆积空穴载流子形成的高空间电荷密度分布区域。晶体内部电场产生扭曲,电子载流子无法迁移至对应阳极位置,导致辐照中心区域产生信号屏蔽效应。     

准随机点阵二值化Gabor波带片聚焦特性的数值计算

Fresnel波带片有多个焦点,作为单色器波长选择元件使用时会受到高级衍射的影响。而Gabor波带片只有一个焦点,有更好的聚焦特性,但制作难度较大,准随机点阵二值化Gabor波带片概念的提出则解决了这个问题。介绍了准随机点阵二值化Gabor波带片的设计,并利用优化的程序分别对Fresnel波带片和准随机点阵二值化Gabor波带片的聚焦特性进行了模拟计算,通过对计算结果进行分析比较,发现准随机点阵二值化Gabor波带片具有抑制高阶衍射的特性。     

一种基于萘酰亚胺的检测细胞内pH值的荧光探针及其生物成像应用

细胞内溶酶体的pH值对细胞自噬、吞噬、酶加工等各项生命活动有着重要影响.细胞核是真核细胞中最大的细胞器,控制着生物体内的遗传和代谢过程,参与代谢过程的酶对pH值的变化很敏感.因此,研究细胞体内的pH值变化至关重要.我们设计并以简单的两步反应合成了一种新型荧光探针NpH-1.该探针以萘酰亚胺作为荧光团,以吗啉基团作为对p...     

螺旋CT成像联合血清copeptin、IL-18水平检测在急性脑梗死患者神经功能及预后评估中的应用价值

本文选取74例急性脑梗死(ACI)患者作为研究对象,入院时根据美国国立卫生院卒中量表(NIHSS)评分分为重度组(NIHSS评分＞15分,n=21)、中度组(NIHSS评分5?15分,n=24)、轻度组(NIHSS评分＜5分,n=29),均接受血清copeptin和IL-18水平检测及螺旋CT成像检查.结果发现,随AC...