An PH-driven DNA Nanodevice for Impeding Metastasis by Selectively Blocking Cell Signaling

Overview

Journal Natl Sci Rev

Date 2025 Mar 5

PMID 40041032

Authors

Kun Yuan

Hong-Min Meng

Hongzhi Sun

Lingbo Qu

Zhaohui Li

Weihong Tan

Affiliations

Soon will be listed here.

Abstract

Invasion and metastasis dominate tumor progression, causing a substantial proportion of cancer-related deaths. However, the efficacy of current antimetastatic treatments is hampered by the dearth of targeted therapeutics. Recently developed synthetic-receptor toolkits offer potential for artificially regulating cellular behavior. However, to the best of our knowledge, none has yet successfully suppressed tumor metastasis . Here, we report the first extracellular pH (pH)-driven DNA nanodevice for use in antimetastatic treatment by manipulating heterogeneous receptors on the tumor cell surface. This DNA nanodevice was constructed by partially locking tumorigenic receptor-specific aptamers with two i-motifs. Acidic extracellular pH induced dynamic allosteric reassembly within the nanodevice. The restructured nanodevice enabled oligomerization of c-Met and transferrin receptor, which inhibited tumor metastasis by blocking the hepatic growth factor (HGF)/c-Met signaling pathway. A suppressive efficacy of 86.25% was verified in an early hepatocarcinoma-pulmonary-metastasis mouse model. Such impressive antimetastatic efficacy suggests an efficient paradigm for developing adaptive antimetastatic therapeutics.

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