The focus of nanoparticles in vivo trafficking has been mostly on their tissue-level biodistribution and clearance. Recent progress in the nanomedicine field suggests that the targeting of nanoparticles to immune cells can be used to modulate the immune response and enhance therapeutic delivery to the diseased tissue. In the presence of tumor lesions, monocytic-myeloid-derived suppressor cells (M-MDSCs) expand significantly in the bone marrow, egress into peripheral blood, and traffic to the solid tumor, where they help maintain an immuno-suppressive tumor microenvironment. In this study, we investigated the interaction between PAMAM dendrimers and M-MDSCs in two murine models of glioblastoma, by examining the cell-level biodistribution kinetics of the systemically injected dendrimers. We found that M-MDSCs in the tumor and lymphoid organs can efficiently endocytose hydroxyl dendrimers. Interestingly, the trafficking of M-MDSCs from the bone marrow to the tumor contributed to the deposition of hydroxyl dendrimers in the tumor. M-MDSCs showed different capacities of endocytosing dendrimers of different functionalities in vivo. This differential uptake was mediated by the unique serum proteins associated with each dendrimer surface functionality. The results of this study set up the framework for developing dendrimer-based immunotherapy to target M-MDSCs for cancer treatment.

中文翻译：

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使用树枝状聚合物及其细胞水平生物分布动力学系统靶向单核细胞骨髓源性抑制细胞


纳米颗粒体内运输的焦点主要集中在其组织水平的生物分布和清除上。纳米医学领域的最新进展表明，纳米颗粒靶向免疫细胞可用于调节免疫反应并增强对患病组织的治疗递送。在存在肿瘤病变的情况下，单核细胞骨髓源性抑制细胞（M-MDSC）在骨髓中显着扩增，进入外周血，并运输到实体瘤，在那里它们帮助维持免疫抑制的肿瘤微环境。在这项研究中，我们通过检查系统注射的树枝状聚合物的细胞水平生物分布动力学，研究了两种胶质母细胞瘤小鼠模型中 PAMAM 树枝状聚合物和 M-MDSC 之间的相互作用。我们发现肿瘤和淋巴器官中的M-MDSC可以有效地内吞羟基树枝状聚合物。有趣的是，M-MDSC 从骨髓运输到肿瘤有助于羟基树枝状聚合物在肿瘤中的沉积。 M-MDSCs 在体内表现出不同功能的内吞不同功能的树枝状聚合物的能力。这种差异吸收是由与每种树枝状聚合物表面功能相关的独特血清蛋白介导的。这项研究的结果为开发基于树状聚合物的免疫疗法以靶向 M-MDSC 进行癌症治疗奠定了框架。