Screening a DNA Aptamer Specifically Targeting Integrin & beta;3 and Partially Inhibiting Tumor Cell Migration

Due to its key roles in malignant tumor progression andreprogramingof the tumor microenvironment, integrin & beta;3 has attracted greatattention as a new target for tumor therapy. However, the structure-functionrelationship of integrins & beta;3 remains incompletely understood,leading to the shortage of specific and effective targeting probes.This work uses a purified extracellular domain of integrin & beta;3and integrin & beta;3-positive cells to screen aptamers, specificallytargeting integrin & beta;3 in the native conformation on live cellsthrough the SELEX approach. Following meticulous truncation and characterizationof the initial aptamer candidates, the optimized aptamer S10yh2 wasproduced, exhibiting a low equilibrium dissociation constant (K (d)) in the nanomolar range. S10yh2 displays specificrecognition of cancer cells with varying levels of integrin & beta;3expression and demonstrates favorable stability in serum. Subsequentanalysis of docking sites revealed that S10yh2 binds to the sevenamino acid residues located in the core region of integrin & beta;3.The S10yh2 aptamer can downregulate the level of integrin heterodimer & alpha;v & beta;3 on integrin & beta;3 overexpressed cancer cells andpartially inhibit cell migration behavior. In summary, S10yh2 is apromising probe with a small size, simple synthesis, good stability,high binding affinity, and selectivity. It therefore holds great potentialfor investigating the structure-function relationship of integrins.