免疫疗法
癌症
中性粒细胞弹性蛋白酶
生物标志物
癌症研究
癌症免疫疗法
医学
免疫学
生物
内科学
炎症
生物化学
作者
Penghui Cheng,Shasha He,Chi Zhang,Jing Liu,Kanyi Pu
标识
DOI:10.1002/anie.202301625
摘要
Abstract NETosis, the peculiar type of neutrophil death, plays important roles in pro‐tumorigenic functions and inhibits cancer immunotherapy. Non‐invasive real‐time imaging is thus imperative for prognosis of cancer immunotherapy yet remains challenging. Herein, we report a T andem‐locked N ETosis R eporter 1 (TNR 1 ) that activates fluorescence signals only in the presence of both neutrophil elastase (NE) and cathepsin G (CTSG) for the specific imaging of NETosis. In the aspect of molecular design, the sequence of biomarker‐specific tandem peptide blocks can largely affect the detection specificity towards NETosis. In live cell imaging, the tandem‐locked design allows TNR 1 to differentiate NETosis from neutrophil activation, while single‐locked reporters fail to do so. The near‐infrared signals from activated TNR 1 in tumor from living mice were consistent with the intratumoral NETosis levels from histological results. Moreover, the near‐infrared signals from activated TNR 1 negatively correlated with tumor inhibition effect after immunotherapy, thereby providing prognosis for cancer immunotherapy. Thus, our study not only demonstrates the first sensitive optical reporter for noninvasive monitoring of NETosis levels and evaluation of cancer immunotherapeutic efficacy in tumor‐bearing living mice, but also proposes a generic approach for tandem‐locked probe design.
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