中南大学唐建兵团队报道了基于M2样巨噬细胞靶向和极化的肿瘤转移的高灵敏成像。相关研究成果发表在2023年3月29日出版的《美国化学会杂志》。

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，抑制先天免疫以帮助肿瘤细胞逃逸，并重塑微环境以帮助转移细胞生长。然而，在体内，M2样巨噬细胞的实时可视化迁移从未被探索用于监测肿瘤转移过程。

该文中，研究人员制备了一种由具有甘露糖和羟氯喹（HCQ）部分的两亲性嵌段共聚物（表示为M-PHCQ）和NO响应性NIR-II探针（表示为NRP）组成的M2样巨噬细胞靶向一氧化氮（NO）反应纳米探针(NRP@M-PHCQ)。甘露糖部分提供M2样巨噬细胞靶向能力，HCQ部分使M2样巨噬细胞极化为M1样巨噬细胞，NO分泌增强。因此NRP@M-PHCQ被分泌的NO照亮，实时观察M2样巨噬细胞的迁移和极化。体内转移成像NRP@M-PHCQ成功地以高灵敏度追踪了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，这表明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，该项工作提供了一种新的策略，通过跟踪M2样巨噬细胞的极化来敏感地成像转移性肿瘤，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。

附：英文原文

Title: Highly Sensitive Imaging of Tumor Metastasis Based on the Targeting and Polarization of M2-like Macrophages

Author: Pengcheng Yuan, Xiaodan Xu, Doudou Hu, Yong Chen, Jiaqi Fan, Shasha Yao, Ying Piao, Zhuxian Zhou, Shiqun Shao, Nigel K. H. Slater, Youqing Shen, Jianbin Tang

Issue&Volume: March 29, 2023

Abstract: 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.

DOI: 10.1021/jacs.2c13218

Source: https://pubs.acs.org/doi/10.1021/jacs.2c13218