Department of Bioengineering, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, United States.
Micro and Nanotechnology Laboratory, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, United States.
ACS Nano. 2022 Feb 22;16(2):1999-2012. doi: 10.1021/acsnano.1c07010. Epub 2022 Feb 2.
Macrophages are white blood cells with diverse functions contributing to a healthy immune response as well as the pathogenesis of cancer, osteoarthritis, atherosclerosis, and obesity. Due to their pleiotropic and dynamic nature, tools for imaging and tracking these cells at scales spanning the whole body down to microns could help to understand their role in disease states. Here we report fluorescent and radioisotopic quantum dots (QDs) for multimodal imaging of macrophage cells , , and . Macrophage specificity is imparted by click-conjugation to dextran, a biocompatible polysaccharide that natively targets these cell types. The emission spectral band of the crystalline semiconductor core was tuned to the near-infrared for optical imaging deep in tissue, and probes were covalently conjugated to radioactive iodine for nuclear imaging. The performance of these probes was compared with all-organic dextran probe analogues in terms of their capacity to target macrophages in visceral adipose tissue using positron emission tomography/computed tomography (PET/CT) imaging, fluorescence imaging, fluorescence, post-mortem isotopic analyses, and optical microscopy. All probe classes exhibited equivalent physicochemical characteristics in aqueous solution and similar targeting specificity. However, dextran-mimetic QDs provided enhanced signal-to-noise ratio for improved optical quantification, long-term photostability, and resistance to chemical fixation. In addition, the vascular circulation time for the QD-based probes was extended 9-fold compared with dextran, likely due to differences in conformational flexibility. The enhanced photophysical and photochemical properties of dextran-mimetic QDs may accelerate applications in macrophage targeting, tracking, and imaging across broad resolution scales, particularly advancing capabilities in single-cell and single-molecule imaging and quantification.
巨噬细胞是具有多种功能的白细胞，有助于健康的免疫反应以及癌症、骨关节炎、动脉粥样硬化和肥胖的发病机制。由于其多效性和动态特性，用于在从全身到微米的范围内对这些细胞进行成像和跟踪的工具可以帮助我们了解它们在疾病状态下的作用。在这里，我们报告了用于巨噬细胞细胞的多模式成像的荧光和放射性同位素量子点 (QD) ， ，和 。通过点击化学将葡聚糖（一种生物相容性多糖，天然靶向这些细胞类型）偶联到葡聚糖上，赋予巨噬细胞特异性。该晶态半导体核的发射光谱带被调谐到近红外，以进行组织深处的光学成像，并将探针共价偶联到放射性碘以进行核成像。这些探针的性能与全有机葡聚糖探针类似物进行了比较，这些探针在使用正电子发射断层扫描/计算机断层扫描 (PET/CT) 成像、荧光成像、荧光、死后同位素分析和光学显微镜检测内脏脂肪组织中的巨噬细胞方面的靶向能力。所有探针类别在水溶液中均表现出等效的物理化学特性，并且具有相似的靶向特异性。然而，葡聚糖模拟 QD 提供了增强的信噪比，用于改善光学定量、长期光稳定性和对化学固定的抗性。此外，与葡聚糖相比，基于 QD 的探针的血管循环时间延长了 9 倍，这可能是由于构象灵活性的差异。葡聚糖模拟 QD 的增强光物理和光化学特性可能会加速在广泛分辨率范围内进行巨噬细胞靶向、跟踪和成像的应用，特别是在单细胞和单分子成像和定量方面的应用。
