Cell Membrane-Anchored DNA Nanoinhibitor for Inhibition of Receptor Tyrosine Kinase Signaling Pathways via Steric Hindrance and Lysosome-Induced Protein Degradation.

Autor:	Tang J; School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450001, Henan, China., Qi C; School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450001, Henan, China., Bai X; School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450001, Henan, China., Ji M; School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450001, Henan, China., Wang Z; School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450001, Henan, China., Luo Y; School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450001, Henan, China., Ni S; School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450001, Henan, China., Zhang T; School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450001, Henan, China., Liu K; School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450001, Henan, China.; Henan Provincial Cooperative Innovation Center for Cancer Chemoprevention, Zhengzhou 450000, Henan, China.; State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou 450001, Henan, China.; China-US (Henan) Hormel Cancer Institute, Zhengzhou 450003, Henan, China.; Cancer Chemoprevention International Collaboration Laboratory, Zhengzhou 450000, Henan, China., Yuan B; School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450001, Henan, China.; Henan Provincial Cooperative Innovation Center for Cancer Chemoprevention, Zhengzhou 450000, Henan, China.; State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou 450001, Henan, China.
Jazyk:	angličtina
Zdroj:	ACS pharmacology & translational science [ACS Pharmacol Transl Sci] 2023 Dec 12; Vol. 7 (1), pp. 110-119. Date of Electronic Publication: 2023 Dec 12 (Print Publication: 2024).
DOI:	10.1021/acsptsci.3c00190
Abstrakt:	Receptor tyrosine kinase (RTK) plays a crucial role in cancer progression, and it has been identified as a key drug target for cancer targeted therapy. Although traditional RTK-targeting drugs are effective, there are some limitations that potentially hinder the further development of RTK-targeting drugs. Therefore, it is urgently needed to develop novel, simple, and general RTK-targeting inhibitors with a new mechanism of action for cancer targeted therapy. Here, a cell membrane-anchored RTK-targeting DNA nanoinhibitor is developed to inhibit RTK function. By using a DNA tetrahedron as a framework, RTK-specific aptamers as the recognition elements, and cholesterol as anchoring molecules, this DNA nanoinhibitor could rapidly anchor on the cell membrane and specifically bind to RTK. Compared with traditional RTK-targeting inhibitors, this DNA nanoinhibitor does not need to bind at a limited domain on RTK, which increases the possibilities of developing RTK inhibitors. With the cellular-mesenchymal to epithelial transition factor (c-Met) as a target RTK, the DNA nanoinhibitor can not only induce steric hindrance effects to inhibit c-Met activation but also reduce the c-Met level via lysosome-mediated protein degradation and thus inhibition of c-Met signaling pathways and related cell behaviors. Moreover, the DNA nanoinhibitor is feasible for other RTKs by just replacing aptamers. This work may provide a novel, simple, and general RTK-targeting nanoinhibitor and possess great value in RTK-targeted cancer therapy. Competing Interests: The authors declare no competing financial interest. (© 2023 American Chemical Society.)
Databáze:	MEDLINE
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