基于 BODIPY 的 NO 探针用于巨噬细胞靶向免疫治疗反应监测,Analytical Chemistry

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基于 BODIPY 的 NO 探针用于巨噬细胞靶向免疫治疗反应监测
Analytical Chemistry ( IF 6.7 ) Pub Date : 2023-04-27 , DOI: 10.1021/acs.analchem.3c00409
Xudong Li ₁ , Hui Chen ₂ , Yuran Wang ₁ , Haijun Chen ₂ , Yu Gao ₁

Affiliation

准确快速地检测免疫反应对于及时调整治疗方案至关重要。肿瘤相关巨噬细胞 (TAM) 从促肿瘤发生表型 (M2) 到抗肿瘤发生表型 (M1) 的免疫调节在巨噬细胞靶向免疫治疗中至关重要。在此，我们开发了一种基于硼二吡咯甲烯 (BODIPY) 的荧光探针BDP3，通过监测 M1 TAM 释放的一氧化氮 (NO) 来检测免疫治疗后的免疫反应。具有芳香伯单胺结构和中间位置的对甲氧基苯胺电子供体，BDP3不仅通过光诱导电子转移 (PET) 过程通过 NO 特异性激活稳定和敏感的荧光，而且还实现了长发射波长，用于有效的体外和体内成像。这种 NO 诱导的BDP3荧光信号经验证与巨噬细胞系和肿瘤组织中检测到的 TAM 表型密切相关。对两种临床使用的免疫治疗药物的不同感知效果进一步证实了BDP3能够特异性监测 M1/M2 开关以响应巨噬细胞靶向免疫治疗。凭借良好的生物相容性和适当的肿瘤保留时间，BDP3可能是一种潜在的荧光探针，用于无创评估巨噬细胞靶向免疫治疗对活体动物的免疫治疗效果。

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BODIPY-Based NO Probe for Macrophage-Targeted Immunotherapy Response Monitoring

Precise and rapid detection of immune responses is critical for timely therapeutic regimen adjustment. Immunomodulation of tumor-associated macrophages (TAMs) from a protumorigenic phenotype (M2) to an antitumorigenic phenotype (M1) is crucial in macrophage-targeted immunotherapy. Herein, we developed a boron dipyrromethene (BODIPY)-based fluorescence probe BDP3 to detect the immune responses after immunotherapy by monitoring the nitric oxide (NO) released by M1 TAMs. With an aromatic primary monoamine structure and a p-methoxyanilin electron donor in the meso-position, BDP3 not only specifically activates stable and sensitive fluorescence by NO via a photoinduced electron transfer (PET) process but also achieves a long emission wavelength for efficient in vitro and in vivo imaging. Such NO-induced fluorescence signals of BDP3 are validated to correlate well with the phenotypes of TAMs detected in macrophage cell lines and tumor tissues. The distinct sensing effects toward two types of clinically used immunotherapeutic drugs further confirm the ability of BDP3 for specific monitoring of the M1/M2 switch in response to the macrophage-targeted immunotherapy. By virtue of good biocompatibility and appropriate tumor retention time, BDP3 could be a potential fluorescent probe for noninvasive evaluation of the immunotherapeutic efficacy of macrophage-targeted immunotherapy in living animals.

更新日期：2023-04-27

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