Nanosystems for monitoring and tracking T cells provide an important basis for evaluating the functionality and efficacy of T cell-based immunotherapy. To this end, we designed herein an efficient nanoprobe for T cell monitoring and tracking using poly(amidoamine) (PAMAM) dendrimer-entrapped gold nanoparticles (Au DENPs) conjugated with Fluo-4 for dual-mode computed tomography (CT) and fluorescence imaging. In this study, PAMAM dendrimers of generation 5 (G5) were modified with hydroxyl-terminated polyethylene glycol (PEG) and then used to entrap 2.0 nm Au NPs followed by acetylation of the excess amine groups on the dendrimer surface. Subsequently, the calcium ion probe was covalently attached to the dendrimer nanohybrids through the PEG hydroxyl end groups to gain the functional {(Au⁰)₂₅-G5.NHAc-(PEG)₁₄-(Fluo-4)₂} nanoprobe. This nanoprobe had excellent water solubility, high X-ray attenuation coefficient, and good cytocompatibility in the given concentration range, as well as a high T cell labeling efficiency. Confocal microscopy and flow cytometry results demonstrated that the nanoprobe was able to fluorescently sense activated T cells. Moreover, the nanoprobe was able to realize both CT and fluorescence imaging of subcutaneously injected T cells in vivo. Thus, the developed novel dendrimer-based nanosystem may hold great promise for advancing and improving the clinical application of T cell-based immunotherapy.

中文翻译：

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多功能树枝状聚合物包裹的金纳米颗粒，用于通过双模态计算机断层扫描和荧光成像标记和追踪T细胞。

监测和追踪T细胞的纳米系统为评估基于T细胞的免疫疗法的功能和功效提供了重要的基础。为此，我们在本文中设计了一种有效的纳米探针，用于T细胞的监测和跟踪，该方法使用掺有Fluo-4的聚酰胺基胺（PAMAM）树枝状聚合物包裹的金纳米颗粒（Au DENPs）进行双模计算机断层扫描（CT）和荧光成像。在这项研究中，用羟基封端的聚乙二醇（PEG）修饰了第5代（G5）的PAMAM树状聚合物，然后用于捕获2.0 nm Au NP，然后在树状聚合物表面上乙酰化了多余的胺基。随后，将钙离子探针通过PEG羟基端基共价连接至树枝状聚合物纳米杂化物，从而获得功能性{（Au ⁰）₂₅-G5.NHAc-（PEG）_14-（Fluo-4）₂ }纳米探针。这种纳米探针在给定的浓度范围内具有极佳的水溶性，高X射线衰减系数和良好的细胞相容性，以及高T细胞标记效率。共聚焦显微镜和流式细胞仪结果表明，纳米探针能够荧光检测活化的T细胞。而且，纳米探针能够在体内实现皮下注射的T细胞的CT和荧光成像。因此，开发的新颖的基于树状聚合物的纳米系统对于推进和改善基于T细胞的免疫疗法的临床应用可能具有广阔的前景。