2. Academic Validation
  3. Selective inhibition of c-Met signaling pathways with a bispecific DNA nanoconnector for the targeted therapy of cancer

Selective inhibition of c-Met signaling pathways with a bispecific DNA nanoconnector for the targeted therapy of cancer

  • Int J Biol Macromol. 2024 Jun 13;273(Pt 2):133134. doi: 10.1016/j.ijbiomac.2024.133134.
Cuihua Qi 1,  Wei Li 1,  Yanchao Luo 1,  Shanshan Ni 1,  Mengmeng Ji 1,  Zhaoting Wang 1,  Tianlu Zhang 1,  Xue Bai 1,  Jinlu Tang 2,  Baoyin Yuan 3,  Kangdong Liu 4
Affiliations

Affiliations

  • 1 School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450001, Henan, China.
  • 2 School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450001, Henan, China; State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou 450001, Henan, China. Electronic address: tangjl@zzu.edu.cn.
  • 3 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. Electronic address: yuanbaoyin@zzu.edu.cn.
  • 4 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.
PMID: 38876234 DOI: 10.1016/j.ijbiomac.2024.133134
Abstract

Hepatocyte growth factor receptor (c-Met) is a suitable molecular target for the targeted therapy of Cancer. Novel c-Met-targeting drugs need to be developed because conventional small-molecule inhibitors and Antibodies of c-Met have some limitations. To synthesize such drugs, we developed a bispecific DNA nanoconnector (STPA) to inhibit c-Met function. STPA was constructed by using DNA triangular prism as a scaffold and Aptamers as binding molecules. After c-Met-specific SL1 and nucleolin-specific AS1411 Aptamers were integrated with STPA, STPA could bind to c-Met and nucleolin on the cell membrane. This led to the formation of the c-Met/STPA/nucleolin complex, which in turn blocked c-Met activation. In vitro experiments showed that STPA could not only inhibit the c-Met signaling pathways but also facilitate c-Met degradation through lysosomes. STPA also inhibited c-Met-promoted cell migration, invasion, and proliferation. The results of in vivo experiments showed that STPA could specifically target to tumor site in xenograft mouse model, and inhibit tumor growth with low toxicity by downregulating c-Met pathways. This study provided a novel and simple strategy to develop c-Met-targeting drugs for the targeted therapy of Cancer.

Keywords

Aptamer; Cancer targeted therapy; DNA nanoconnector.

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