Abstract Tumor-associated macrophages (TAMs) exhibit the M2 phenotype and serve as critical tumor-promoting immune cells in the tumor microenvironment. As TAMs are an important target, we examined the effect of gold nanoparticles (AuNPs) with radiotherapy (RT) on M2 TAMs in tumors. We synthesized CD163 antibody-conjugated, silica-coated AuNPs (CD163-GNPs) that were specifically recognized by M2 TAMs. Bone marrow-derived macrophages and Raw 264.7 macrophages were polarized into M1 and M2 phenotypes. The effect of CD163-GNPs combined with RT was evaluated in a CT26 syngeneic mouse model (BALB/c mice). Immunostaining, flow cytometry, microscopic analyses, enzyme-linked immunosorbent assay, quantitative real-time polymerase chain reaction (qRT-PCR), and tumor growth delay assay were performed following irradiation combined with CD163-GNP treatment. We observed selective phagocytosis of CD163-GNPs by Raw 264.7 macrophages following M1/M2 polarization. Immunostaining analyses revealed higher numbers of CD163-GNPs taken up by M2 macrophages than M0 or M1 type. CD163-GNPs combined with RT significantly reduced tumor growth in the CT26 syngeneic mouse model. Macrophages subjected to the combination treatment showed increased expression of M1 markers. The depletion of M2 TAMs in tumors upon combination treatment with CD163-GNPs enhances the efficiency of RT.

中文翻译：

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通过结合靶向肿瘤相关巨噬细胞的 Au@SiO2 纳米粒子增强放疗的抗肿瘤作用

摘要 肿瘤相关巨噬细胞 (TAM) 表现出 M2 表型，是肿瘤微环境中关键的促肿瘤免疫细胞。由于 TAMs 是一个重要的靶点，我们研究了金纳米粒子 (AuNPs) 与放疗 (RT) 对肿瘤中 M2 TAMs 的影响。我们合成了 CD163 抗体偶联的、二氧化硅包覆的 AuNPs (CD163-GNPs)，它被 M2 TAMs 特异性识别。骨髓来源的巨噬细胞和 Raw 264.7 巨噬细胞被极化为 M1 和 M2 表型。CD163-GNPs 与 RT 结合的效果在 CT26 同源小鼠模型 (BALB/c 小鼠) 中进行了评估。免疫染色、流式细胞术、显微镜分析、酶联免疫吸附测定、定量实时聚合酶链反应 (qRT-PCR) 和肿瘤生长延迟测定在辐照和 CD163-GNP 治疗后进行。我们观察到原始 264.7 巨噬细胞在 M1/M2 极化后选择性吞噬 CD163-GNP。免疫染色分析显示，与 M0 或 M1 型相比，M2 巨噬细胞吸收的 CD163-GNP 数量更多。CD163-GNPs 联合放疗显着降低了 CT26 同源小鼠模型中的肿瘤生长。接受联合治疗的巨噬细胞表现出 M1 标志物的表达增加。在与 CD163-GNP 联合治疗后，肿瘤中 M2 TAM 的消耗提高了放疗的效率。接受联合治疗的巨噬细胞表现出 M1 标志物的表达增加。在与 CD163-GNP 联合治疗后，肿瘤中 M2 TAM 的消耗提高了放疗的效率。接受联合治疗的巨噬细胞表现出 M1 标志物的表达增加。在与 CD163-GNP 联合治疗后，肿瘤中 M2 TAM 的消耗提高了放疗的效率。