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


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.

SUBMITTER: Wu X 

PROVIDER: S-EPMC6625514 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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

Wu Xiaoqiu X   Liu Honglin H   Han Dongmei D   Peng Bo B   Zhang Hui H   Zhang Lin L   Li Jianglin J   Liu Jing J   Cui Cheng C   Fang Senbiao S   Li Min M   Ye Mao M   Tan Weihong W  

Journal of the American Chemical Society 20190701 27


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 aff  ...[more]

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