Elucidation and Structural Modeling of CD71 as a Molecular Target for Cell-Specific Aptamer Binding

  • J Am Chem Soc. 2019 Jul 10;141(27):10760-10769. doi: 10.1021/jacs.9b03720.
Xiaoqiu Wu  1 ,  Honglin Liu  1  2 ,  Dongmei Han  1 ,  Bo Peng  1 ,  Hui Zhang  1 ,  Lin Zhang  1 ,  Jianglin Li  1 ,  Jing Liu ,  Cheng Cui  1  3 ,  Senbiao Fang ,  Min Li ,  Mao Ye  1 ,  Weihong Tan  1  3  4
Affiliations
  • 1. Molecular Science and Biomedicine Laboratory (MBL), State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Biology, College of Chemistry and Chemical Engineering, Aptamer Engineering Center of Hunan Province , Hunan University , Changsha , Hunan 410082 , China.
  • 2. School of Food and Biological Engineering , Hefei University of Technology , Hefei , Anhui 230009 , China.
  • 3. Department of Chemistry and Department of Physiology and Functional Genomics, Center for Research at the Bio/Nano Interface, Health Cancer Center, UF Genetics Institute, McKnight Brain Institute , University of Florida , Gainesville , Florida 32611 , United States.
  • 4. Institute of Molecular Medicine (IMM), Renji Hospital, Shanghai Jiao Tong University School of Medicine, and College of Chemistry and Chemical Engineering , Shanghai Jiao Tong University , Shanghai 200240 , China.
PMID: 31185171 DOI: 10.1021/jacs.9b03720
Abstract

Pancreatic Cancer is a highly lethal malignancy associated with tissues of the pancreas. Early diagnosis and effective treatment are crucial to improving the survival rate of patients with pancreatic Cancer. In a previous study, we employed the cell-SELEX strategy to obtain an ssDNA aptamer termed XQ-2d with high binding affinity for pancreatic Cancer. Here, we first identify CD71 as the XQ-2d-binding target. We found that knockdown of CD71 abolished the binding of XQ-2d and that the binding affinity of XQ-2d is associated with membrane-bound CD71, rather than total CD71 levels. Competitive analysis revealed that XQ-2d shares the same binding site on CD71 with transferrin (Tf), but not anti-CD71 antibody. We then used a surface energy transfer (SET) nanoruler to measure the distance between the binding sites of XQ-2d and anti-CD71 antibody, and it was about 15 nm. Furthermore, we did molecular dynamics simulation to clarify that the spatial structure of XQ-2d and Tf competitively binding to CD71. We also engineered XQ-2d-mediated targeted therapy for pancreatic Cancer, using an XQ-2d-based complex for loading doxorubicin (Dox). Because CD71 is overexpressed not only in pancreatic Cancer but also in a variety of tumors, our work provides a systematic novel way of studying a potential biomarker and also promising tools for Cancer diagnosis and therapy, opening new doors for effective Cancer theranostics.

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