Screening a DNA Aptamer Specifically Targeting Integrin β3 and Partially Inhibiting Tumor Cell Migration

Due to its key roles in malignant tumor progression and reprograming of the tumor microenvironment, integrin β3 has attracted great attention as a new target for tumor therapy. However, the structure–function relationship of integrins β3 remains incompletely understood, leading to the shortage of sp...

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Bibliographic Details
Published in:Analytical chemistry (Washington) 2023-08, Vol.95 (33), p.12406-12418
Main Authors: Teng, Xiaoyan, Wang, Yu, You, Liuxia, Wei, Lirong, Zhang, Chao, Du, Yuzhen
Format: Article
Language:English
Subjects:
Amino acids
Analytical chemistry
Aptamers
Cancer
Cancer therapies
Cell adhesion & migration
Cell migration
Conformation
DNA probes
Integrins
Stability analysis
Structure-function relationships
Tumor microenvironment
Tumors
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Summary:Due to its key roles in malignant tumor progression and reprograming of the tumor microenvironment, integrin β3 has attracted great attention as a new target for tumor therapy. However, the structure–function relationship of integrins β3 remains incompletely understood, leading to the shortage of specific and effective targeting probes. This work uses a purified extracellular domain of integrin β3 and integrin β3-positive cells to screen aptamers, specifically targeting integrin β3 in the native conformation on live cells through the SELEX approach. Following meticulous truncation and characterization of the initial aptamer candidates, the optimized aptamer S10yh2 was produced, exhibiting a low equilibrium dissociation constant (K d) in the nanomolar range. S10yh2 displays specific recognition of cancer cells with varying levels of integrin β3 expression and demonstrates favorable stability in serum. Subsequent analysis of docking sites revealed that S10yh2 binds to the seven amino acid residues located in the core region of integrin β3. The S10yh2 aptamer can downregulate the level of integrin heterodimer αvβ3 on integrin β3 overexpressed cancer cells and partially inhibit cell migration behavior. In summary, S10yh2 is a promising probe with a small size, simple synthesis, good stability, high binding affinity, and selectivity. It therefore holds great potential for investigating the structure–function relationship of integrins.
ISSN:0003-2700
1520-6882
DOI:10.1021/acs.analchem.3c01995