Diagnosing Orthotopic Lung Tumor Using a NTR-Activatable Near-Infrared Fluorescent Probe by Tracheal Inhalation,Analytical Chemistry

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Diagnosing Orthotopic Lung Tumor Using a NTR-Activatable Near-Infrared Fluorescent Probe by Tracheal Inhalation
Analytical Chemistry ( IF 6.7 ) Pub Date : 2023-09-12 , DOI: 10.1021/acs.analchem.3c02760
Jun Yan ₁ , Kaizhen Wang ₁ , Lijuan Gui ₁ , Xian Liu ₂ , Yingying Ji ₁ , Jingjing Lin ₁ , Man Luo ₁ , Hong Xu ₁ , Jingxuan Lv ₁ , Fang Tan ₃ , Liangting Lin ₂ , Zhenwei Yuan ₁

Affiliation

Nitroreductase (NTR) is an enzyme that is upregulated under tumor-depleted oxygen conditions. The majority of studies have been conducted on NTR, but many existing fluorescent imaging tools for monitoring NTR inevitably suffer from weak targeting, low sensitivity, and simple tumor models. Research on diagnosing lung tumors has been very popular in recent years, but targeting assays in orthotopic lung tumors is still of great research value, as such models better mimic the reality of cancer in the organism. Here, we developed a novel near-infrared (NIR) fluorescent probe IR-ABS that jointly targets NTR and carbonic anhydrase IX (CAIX). IR-ABS has excellent sensitivity and selectivity and shows exceptional NTR response in spectroscopic tests. The measurements ensured that this probe has good biosafety in both cells and mice. A better NTR response was found in hypoxic tumor cells at the cellular level, distinguishing tumor cells from normal cells. In vivo experiments demonstrated that IR-ABS achieves a hypoxic response at the zebrafish level and enables rapid and accurate tumor margin distinguishment in different mouse tumor models. More importantly, we successfully applied IR-ABS for NTR detection in orthotopic lung tumor models, further combined with tracheal inhalation drug delivery to improve targeting. To the best of our knowledge, we present for the first time a near-infrared imaging method for targeting lung cancerous tumor in situ via tracheal inhalation drug delivery, in contrast to the reported literature. This NIR fluorescence diagnostic strategy for targeting orthotopic lung cancer holds exciting potential for clinical aid in cancer diagnosis.

中文翻译：

使用 NTR 可激活近红外荧光探针通过气管吸入诊断原位肺肿瘤

硝基还原酶 (NTR) 是一种在肿瘤缺氧条件下上调的酶。大多数研究都是针对NTR进行的，但许多现有的监测NTR的荧光成像工具不可避免地存在靶向性弱、灵敏度低和肿瘤模型简单等问题。近年来，诊断肺肿瘤的研究非常流行，但原位肺肿瘤的靶向测定仍然具有很大的研究价值，因为此类模型可以更好地模拟生物体中癌症的现实。在这里，我们开发了一种新型近红外（NIR）荧光探针IR-ABS，它联合靶向NTR和碳酸酐酶IX（CAIX）。IR-ABS具有出色的灵敏度和选择性，并在光谱测试中表现出出色的 NTR 响应。测量结果确保该探针在细胞和小鼠中均具有良好的生物安全性。在细胞水平上，缺氧肿瘤细胞中发现了更好的 NTR 反应，从而将肿瘤细胞与正常细胞区分开来。体内实验表明，IR-ABS能够实现斑马鱼水平的缺氧反应，并能够在不同的小鼠肿瘤模型中快速准确地区分肿瘤边缘。更重要的是，我们成功地将IR-ABS应用于原位肺肿瘤模型中的NTR检测，并进一步结合气管吸入给药以提高靶向性。据我们所知，我们首次提出了一种通过气管吸入药物输送原位靶向肺癌肿瘤的近红外成像方法，与报道的文献相反。这种针对原位肺癌的近红外荧光诊断策略在癌症诊断的临床辅助方面具有令人兴奋的潜力。

更新日期：2023-09-12

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