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通过肿瘤相关巨噬细胞特异性一氧化氮的比率近红外荧光成像可视化抗肿瘤药物的疗效

Visualizing Efficacy of Antineoplastic Drug via Ratiometric Near-Infrared Fluorescence Imaging of Tumor-Associated Macrophage-Specific Nitric Oxide.

作者信息

Wu Chuanchen, Zhang Fanghui, Mao Yuantao, Qi Xinru, Wang Xin, Zhang Wen, Tang Bo, Li Ping

机构信息

College of Chemistry, Chemical Engineering and Materials Science, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Institutes of Biomedical Sciences, Shandong Normal University, Jinan 250014, People's Republic of China.

出版信息

Chem Biomed Imaging. 2023 Mar 13;1(4):372-379. doi: 10.1021/cbmi.3c00016. eCollection 2023 Jul 24.

DOI:10.1021/cbmi.3c00016
PMID:39473936
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11503663/
Abstract

Elevated nitric oxide (NO) within tumor-associated macrophages (TAMs) suggests a reduction of TAM-mediated tumoral immune tolerance. This cellular event could be a reliable indicator for efficacy evaluation of antineoplastic drugs. However, a suitable method for TAM-specific NO measurement is still lacking. In this work, a simple and fast efficacy evaluation method for antineoplastic drugs is established based on a ratiometric TAM-specific NO near-infrared (NIR) fluorescence probe TAM-Cy-NO. Molecular fluorescence probe Cy-NO for NO response was encapsulated in the TAM-targeting peptide (M2pep)-functionalized liposome to construct TAM-Cy-NO. After TAM enters through M2pep, Cy-NO reacts with NO specifically, resulting in a dose-dependent ratiometric fluorescence signal ( / ) change manner. Utilizing this strategy, we observed that PLX-3397, metformin, and ibrutinib triggered NO generation within TAM greater than that with sorafenib. Notably, metformin and ibrutinib promoted TNF-α and reduced PD-L1 expressions, which suggest reductions of TAM-mediated immunosuppression. As expected, these drugs delayed tumor progression in mice. This method provides a promising efficacy evaluation strategy for rapid screening of antineoplastic drugs.

摘要

肿瘤相关巨噬细胞（TAM）中一氧化氮（NO）水平升高表明TAM介导的肿瘤免疫耐受降低。这一细胞事件可能是抗肿瘤药物疗效评估的可靠指标。然而，仍缺乏一种适用于特异性测量TAM中NO的方法。在这项工作中，基于比率型TAM特异性NO近红外（NIR）荧光探针TAM-Cy-NO，建立了一种简单快速的抗肿瘤药物疗效评估方法。将对NO有响应的分子荧光探针Cy-NO包裹在靶向TAM的肽（M2pep）功能化脂质体中，构建TAM-Cy-NO。TAM通过M2pep进入后，Cy-NO与NO特异性反应，导致剂量依赖性的比率荧光信号（ / ）变化方式。利用该策略，我们观察到PLX-3397、二甲双胍和伊布替尼在TAM中引发的NO生成量大于索拉非尼。值得注意的是，二甲双胍和伊布替尼促进了TNF-α的表达并降低了PD-L1的表达，这表明TAM介导免疫抑制作用的降低。正如预期的那样，这些药物延缓了小鼠肿瘤的进展。该方法为快速筛选抗肿瘤药物提供了一种有前景的疗效评估策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/577e/11503663/5ff8d97f5e45/im3c00016_0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/577e/11503663/52fee6921502/im3c00016_0007.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/577e/11503663/148116764c23/im3c00016_0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/577e/11503663/7f97fbd8b813/im3c00016_0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/577e/11503663/5693ab8f2be4/im3c00016_0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/577e/11503663/32f05d71ed2f/im3c00016_0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/577e/11503663/5ff8d97f5e45/im3c00016_0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/577e/11503663/52fee6921502/im3c00016_0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/577e/11503663/6fb83cb4128e/im3c00016_0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/577e/11503663/148116764c23/im3c00016_0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/577e/11503663/7f97fbd8b813/im3c00016_0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/577e/11503663/5693ab8f2be4/im3c00016_0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/577e/11503663/32f05d71ed2f/im3c00016_0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/577e/11503663/5ff8d97f5e45/im3c00016_0006.jpg

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