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

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.

 

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This research describes the development of a nanoprobe (NRP@M-PHCQ) that targets M2-like macrophages in order to track their migration and polarization in real-time during tumor metastasis. The nanoprobe consists of an amphiphilic block copolymer with mannose and hydroxychloroquine (HCQ) moieties that provide M2-like macrophage-targeting capacity and polarize M2-like macrophages to M1-like ones with enhanced NO secretion. The NO-responsive NIR-II probe (NRP) in the nanoprobe is lit up by the secreted NO, allowing for the visualization of the migration and polarization of M2-like macrophages.

In vivo metastasis imaging with NRP@M-PHCQ was able to track early tumor metastasis in the lymph nodes and lungs with high sensitivity, even superior to Luci-labeled bioluminescence imaging. This suggests that M2-like macrophages have an extensive distribution and play a critical role in tumor metastasis.

Overall, this research provides a new strategy to sensitively image metastatic tumors by tracking the polarization of M2-like macrophages and visually discloses the critical role of M2-like macrophages in early tumor metastasis.

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S4430 Hydroxychloroquine (HCQ) Sulfate Hydroxychloroquine (HCQ) Sulfate is an antimalarial agent used for the treatment of systemic lupus erythematosus, rheumatoid arthritis and other autoimmune, inflammatory and dermatologic conditions. Also acts as an inhibitor of autophagy and toll-like receptor (TLR) 7/9.

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