Selection of a novel DNA thioaptamer against HER2 structure
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Y. Hu [4] ; J. Duan [4] ; B. Cao [4] ; L. Zhang [4] ; X. Lu [1] ; F. Wang [1] ; F. Yao [1] ; Z. Zhu [1] ; W. Yuan [2] ; C. Wang [3] ; X.-D. Yang [4]
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[1] Peking Union Medical College Hospital
Peking Union Medical College Hospital
China
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[2] Tianjin Medical University Cancer Institute and Hospital
Tianjin Medical University Cancer Institute and Hospital
China
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[3] National Center for Nanoscience and Technology
National Center for Nanoscience and Technology
China
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[4] Chinese Academy of Medical Sciences, China
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- Localización: Clinical & translational oncology, ISSN 1699-048X, Vol. 17, Nº. 8 (August), 2015, págs. 647-656
- Idioma: inglés
- Texto completo no disponible (Saber más ...)
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Resumen
Purpose Human epithelial growth factor receptor 2 (HER2) is over-expressed in several malignancies and represents an important therapeutic target. Aptamers are oligonucleotides that may potentially serve as tumor-homing ligand with excellent affinity and specificity for targeted cancer therapy. However, aptamers need to have nuclease resistance in order to function in vivo. The aim of this study was to generate a novel HER2 thioaptamer with enhanced nuclease resistance.
Methods The HER2 thioaptamer is selected in an evolutionary process called systematic evolution of ligands by exponential enrichment.
Results The thioaptamer could bind to the extracellular domain of HER2 with a K d of 172 nM and had minimal cross reactivity to trypsin or IgG. Moreover, the thioaptamer was found capable of binding with the HER2-positive breast cancer cells SK-BR-3 and MDA-MB-453, but not the HER2-negative cells MDA-MB-231. Notably, the thioaptamer HY6 largely maintained its structural integrity facing the nucleases in serum, while regular DNA aptamers were mostly digested. Additionally, the thioaptamer retained the capability of binding with the HER2-positive cells in the presence of serum, whereas non-thionated HER2 aptamer lost the binding function.
Conclusion The results indicated that the selected thioaptamer was more resistant to nuclease than regular DNA aptamers and might potentially function as a HER2-targeting ligand in complicated environment.
