癌细胞
癌症研究
免疫疗法
癌症免疫疗法
癌症
生物
细胞生物学
遗传学
作者
Zhaopeng Chen,Weijia Zeng,Yan‐Mei Lei,Yong‐Min Liang,Xia Yang,Ruo Yuan,Chaoyong Yang,Ying Zhuo
标识
DOI:10.1002/anie.202414064
摘要
Granzyme A (GzmA) secreted by natural killer (NK) cells has garnered considerable interest as a biomarker to evaluate the efficacy of cancer immunotherapy. However, current methodologies to selectively monitor the spatial distribution of GzmA in cancer cells during NK cell‐targeted therapy are extremely challenging, primarily due to the existence of diverse cell populations, the low levels of GzmA expression, and the limited availability of GzmA probes. Herein we develop a multi‐modular, structurally‐ordered DNA nanodevice for evaluating NK cell‐mediated cancer immunotherapy (MODERN), that permits spatioselective imaging of GzmA in cancer cells through GzmA‐induced apurinic/apyrimidinic endonuclease 1 (APE1) inactivation. The MODERN incorporates multiple functional modules, including an APE1‐gated recognition module, a photo‐activated amplification module, an aptamer‐mediated tumor‐target module, and a polycatenane DNA module, enabling improved sensitivity and specificity towards intracellular GzmA. The MODERN was activated (on) in cancer cells due to the overexpression of APE1, whereas it remained silent (off) in the NK‐treated cancer cells owing to the GzmA‐induced APE1 inactivation. Furthermore, we demonstrated that GzmA‐induced APE1 inactivation blocks the cellular repair of target cells, resulting in efficient cell death. This MODERN that relies on the specific inactivation of APE1 by GzmA should be beneficial for evaluating the efficacy of cancer immunotherapy.
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