肿瘤相关巨噬细胞，特别是M2型巨噬细胞，在肿瘤生长和转移中扮演了重要角色，抑制先天免疫以帮助肿瘤细胞逃脱，重塑微环境以促进转移细胞生长。然而，在体内，实时可视化的M2型巨噬细胞迁移从未被探究，以监测肿瘤转移过程。因此，我们制备了一种M2型巨噬细胞靶向的亚硝酸(NO)响应型纳米探针(NRP @ M-PHCQ)，由含有甘露糖和羟氯喹(HCQ)基团的两亲共聚物(amphiphilic block copolymer)（称为M-PHCQ）和一个NO响应的NIR-II探针(称为NRP)组成。甘露糖基团提供了M2型巨噬细胞靶向能力，HCQ基团使M2型巨噬细胞极化为M1型巨噬细胞，并增强NO分泌。因此，NRP@M-PHCQ可以由分泌的NO点亮，实时可视化M2型巨噬细胞的迁移和极化。NRP@M-PHCQ在体内转移成像成功追踪了淋巴结和肺的早期肿瘤转移，具有高灵敏度，甚至优于Luci标记的生物发光成像，说明M2型巨噬细胞在肿瘤转移中广泛分布和发挥了关键作用。总的来说，这项工作提供了一种新的策略，通过跟踪M2型巨噬细胞的极化，敏感地成像转移性肿瘤，并在视觉上揭示了M2型巨噬细胞在早期肿瘤转移中的关键作用。

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.