Targeted Imaging of Tumor Associated Macrophages in Breast Cancer
Targeted Imaging of Tumor Associated Macrophages in Breast Cancer
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DOI：
10.15212/bioi-2022-0010
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发表时间：
2022
期刊：
影响因子：
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通讯作者：
Yanni Xu;Yunting Zeng;Xiaoyun Xiao;Hejun Liu;Boyang Zhou;B. Luo;Phei Er Saw;Q. Jiang
中科院分区：
文献类型：
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作者：
Yanni Xu;Yunting Zeng;Xiaoyun Xiao;Hejun Liu;Boyang Zhou;B. Luo;Phei Er Saw;Q. Jiang
乳腺癌是一种缺乏预后标志物的高度异质性疾病。肿瘤微环境中的肿瘤相关巨噬细胞（TAM）与乳腺癌的远处转移以及较差的预后相关。因此，监测 TAM 可以指导预后评估。本研究探索了一种基于两步点击化学程序的成像模式，用于检测乳腺癌中的 TAM。制备了封装 Ac4GalNAz 的甘露糖靶向脂质体 (MAN-lipo-AAG) 和非靶向脂质体 (lipo-AAG) 并进行了全面表征。制备的MAN-lipo-AAG和lipo-AAG的尺寸分别为126±0.22和93±0.23 nm。体外研究表明，RAW264.7 细胞对 MAN-lipo-AAG 的摄取量高于 lipo-AAG。此外，流式细胞术和共聚焦显微镜证实，MAN-lipo-AAG 组的 RAW264.7 细胞膜上存在明亮、均匀的荧光标记。此外，体内分析表明，与 lipo-AAG 相比，MAN-lipo-AAG 在 4T1 异种移植模型中具有更高的积累，并且被甘露糖过表达的 TAM 摄取更高。这项研究描述了一种通过代谢糖工程进行特异性、非侵入性 TAM 靶向成像的有前途的方法。
Breast cancer is a highly heterogeneous disease lacking prognostic markers. Tumor-associated macrophages (TAMs) in the tumor microenvironment are associated with distant metastasis as well as poorer outcomes in breast cancer. Therefore, monitoring TAMs may guide prognostic assessment. This study explores an imaging modality based on a two-step click chemistry procedure for detecting TAMs in breast cancer. Mannose-targeted liposomes (MAN-lipo-AAG) and non-targeted liposomes (lipo-AAG) encapsulating Ac4GalNAz were prepared and comprehensively characterized. The sizes of the prepared MAN-lipo-AAG and lipo-AAG were 126 ± 0.22 and 93 ± 0.23 nm, respectively. In vitro studies demonstrated higher uptake of MAN-lipo-AAG than lipo-AAG by RAW264.7 cells. Moreover, flow cytometry and confocal microscopy confirmed that bright, homogeneous fluorescence labeling was present on RAW264.7 cell membranes in the MAN-lipo-AAG group. Furthermore, in vivo analysis indicated that MAN-lipo-AAG, compared with lipo-AAG, had higher accumulation in a 4T1 xenograft model and higher uptake by mannose-overexpressing TAMs. This study describes a promising approach for specific and non-invasive TAM-targeted imaging via metabolic glycoengineering.