Highly Sensitive Imaging of Tumor Metastasis Based on the Targeting and Polarization of M2-like Macrophages,Journal of the American Chemical Society

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Highly Sensitive Imaging of Tumor Metastasis Based on the Targeting and Polarization of M2-like Macrophages
Journal of the American Chemical Society ( IF 14.4 ) Pub Date : 2023-03-29 , DOI: 10.1021/jacs.2c13218
Pengcheng Yuan ₁ , Xiaodan Xu ₁ , Doudou Hu ₁ , Yong Chen ₁ , Jiaqi Fan ₁ , Shasha Yao ₁ , Ying Piao ₁ , Zhuxian Zhou ₁ , Shiqun Shao ₁ , Nigel K H Slater ₁ , Youqing Shen ₁ , Jianbin Tang ₁

Affiliation

Tumor-associated macrophages, especially M2-like macrophages, are extensively involved in tumor growth and metastasis, suppressing the innate immunity to help tumor cells escape and reshaping the microenvironment to help metastatic cells grow. However, in vivo, real-time visualized migration of M2-like macrophages has never been explored to monitor the tumor metastasis process. Herein, we prepared an M2-like macrophage-targeting nitric oxide (NO)-responsive nanoprobe (NRP@M-PHCQ) consisting of an amphiphilic block copolymer with mannose and hydroxychloroquine (HCQ) moieties (denoted as M-PHCQ) and a NO-responsive NIR-II probe (denoted as NRP). The mannose moieties provided M2-like macrophage-targeting capacity, and the HCQ moieties polarized M2-like macrophages to M1-like ones with enhanced NO secretion. Consequently, NRP@M-PHCQ was lit up by the secreted NO to visualize the migration and polarization of M2-like macrophages in real time. In vivo metastasis imaging with NRP@M-PHCQ successfully tracked early tumor metastasis in the lymph nodes and the lungs with high sensitivity, even superior to Luci-labeled bioluminescence imaging, suggesting the extensive distribution and critical role of M2-like macrophages in tumor metastasis. In general, this work provided a new strategy to sensitively image metastatic tumors by tracking the polarization of M2-like macrophages and visually disclosed the critical role of M2-like macrophages in early tumor metastasis.

中文翻译：

基于 M2 样巨噬细胞靶向和极化的肿瘤转移高灵敏度成像

肿瘤相关巨噬细胞，尤其是M2样巨噬细胞，广泛参与肿瘤生长和转移，抑制先天免疫帮助肿瘤细胞逃逸，重塑微环境帮助转移细胞生长。然而，在体内，从未探索过 M2 样巨噬细胞的实时可视化迁移来监测肿瘤转移过程。在此，我们制备了一种 M2 样巨噬细胞靶向一氧化氮 (NO) 响应纳米探针 ( NRP@M-PHCQ) 由具有甘露糖和羟氯喹 (HCQ) 部分的两亲嵌段共聚物（表示为 M-PHCQ）和 NO 响应 NIR-II 探针（表示为 NRP）组成。甘露糖部分提供了 M2 样巨噬细胞靶向能力，而 HCQ 部分将 M2 样巨噬细胞极化为 M1 样巨噬细胞，并增强了 NO 分泌。因此，NRP@M-PHCQ被分泌的 NO 点亮，实时观察 M2 样巨噬细胞的迁移和极化。NRP@M-PHCQ体内转移成像成功地以高灵敏度追踪淋巴结和肺部的早期肿瘤转移，甚至优于 Luci 标记的生物发光成像，表明 M2 样巨噬细胞在肿瘤转移中的广泛分布和关键作用。总的来说，这项工作提供了一种通过跟踪 M2 样巨噬细胞的极化对转移性肿瘤进行敏感成像的新策略，并直观地揭示了 M2 样巨噬细胞在早期肿瘤转移中的关键作用。

更新日期：2023-03-29

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