Near-Infrared Fluorescent Macromolecular Reporters for Real-Time Imaging and Urinalysis of Cancer Immunotherapy,Journal of the American Chemical Society

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Near-Infrared Fluorescent Macromolecular Reporters for Real-Time Imaging and Urinalysis of Cancer Immunotherapy
Journal of the American Chemical Society ( IF 14.4 ) Pub Date : 2020-03-20 , DOI: 10.1021/jacs.0c00659
Shasha He ₁ , Jingchao Li ₁ , Yan Lyu ₁ , Jiaguo Huang ₁ , Kanyi Pu ₁

Affiliation

Real-time imaging of immunoactivation is imperative for cancer immunotherapy and drug discovery; however, most existing imaging agents possess "always-on" signals and thus have poor signal correlation with immune responses. Herein, renal-clearable near-infrared (NIR) fluorescent macromolecular reporters are synthesized to specifically de-tect an immunoactivation-related biomarker (Granzyme B) for real-time evaluation of cancer immunotherapy. Com-posed of a peptide-caged NIR signaling moiety linked with a hydrophilic poly(ethylene glycol) (PEG) passivation chain, the reporters not only specifically activates its fluorescence by Granzyme B but also passively target the tumor of living mice after systemic administration. Such a Granzyme B induced in vivo signals of the reporters are validated to correlate well with the populations of cytotoxic T lymphocytes (CD8+) and T helper (CD4+) cells detected in tumor tissues. By virtue of its ideal renal clearance efficiency (60% injected doses at 24 h post-injection), the reporters can be used for optical uranalysis of immunoactivation simply by detecting the status of excreted reporters. This study thus proposes a molecular optical imaging approach for noninvasive evaluation of cancer immunotherapeutic efficacy in living animals.

中文翻译：

用于癌症免疫治疗的实时成像和尿液分析的近红外荧光大分子报告基因

免疫激活的实时成像对于癌症免疫治疗和药物发现是必不可少的；然而，大多数现有的显像剂具有“永远在线”的信号，因此与免疫反应的信号相关性很差。在此，合成了可肾脏清除的近红外 (NIR) 荧光大分子报告基因，以特异性检测免疫激活相关的生物标志物 (Granzyme B)，用于实时评估癌症免疫治疗。由与亲水性聚（乙二醇）（PEG）钝化链连接的肽笼式 NIR 信号部分组成，报道分子不仅通过颗粒酶 B 特异性激活其荧光，而且在全身给药后还被动靶向活小鼠的肿瘤。这种由报告基因诱导的体内信号的颗粒酶 B 被证实与在肿瘤组织中检测到的细胞毒性 T 淋巴细胞 (CD8+) 和 T 辅助 (CD4+) 细胞群密切相关。凭借其理想的肾脏清除效率（注射后 24 小时注射剂量为 60%），报告基因只需检测排泄报告基因的状态即可用于免疫激活的光学尿分析。因此，本研究提出了一种分子光学成像方法，用于对活体动物的癌症免疫治疗功效进行无创评估。

更新日期：2020-03-20

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