Selection and characterization of DNA aptamer for metastatic prostate cancer recognition and tissue imaging

2016 
// Minlan Duan 1, * , Yuqian Long 1, * , Cai Yang 1, * , Xiaoqiu Wu 1 , Yang Sun 1 , Jianglin Li 1 , Xiaoxiao Hu 1 , Wei Lin 1 , Dongmei Han 1 , Yifan Zhao 1 , Jing Liu 2 , Mao Ye 1 , Weihong Tan 1, 3, 4 1 Molecular Science and Biomedicine Laboratory, State Key Laboratory for Chemo/Biosensing and Chemometrics, College of Biology, College of Chemistry and Chemical Engineering, Collaborative Innovation Center for Molecular Engineering for Theranostics, Hunan University, Changsha, Hunan 410082, China 2 School of Life Sciences, State Key Laboratory of Medical Genetics, Central South University, Changsha, Hunan 410078, China 3 Department of Chemistry, Center for Research at Bio/Nano Interface, University Health Cancer Center, University of Florida Genetics Institute and McKnight Brain Institute, University of Florida, Gainesville, FL 32611, USA 4 Department of Physiology and Functional Genomics, University of Florida, Gainesville, FL 32611, USA * These authors contributed equally to this work Correspondence to: Weihong Tan, email: tan@chem.ufl.edu Mao Ye, email: yemaocsu@hotmail.com Keywords: prostate cancer, aptamer, SELEX, metastasis, binding affinity Received: January 28, 2016      Accepted: April 02, 2016      Published: May 10, 2016 ABSTRACT Prostate cancer (PCa) is the second leading cause of death and most prevalent cancer in men. The absence of curative options for castration-resistant metastatic prostate cancer and biomarkers able to discriminate between indolent and aggressive tumors contribute to these statistics. In this study, a DNA aptamer termed DML-7 was successfully selected against human PCa cell line DU145 by using the cell-based systematic evolution of ligands by exponential enrichment (SELEX) method. The selected aptamer DML-7 was found to internalize into target cells in a temperature-dependent manner and exhibit high binding affinity for target cells with dissociation constants in the nanomolar range. Binding analysis further revealed that DML-7 only binds to DU145 and PC-3 cells with metastatic potential, but not to LNCaP or 22Rv1 cells with low or nonmetastatic potential, demonstrating that DML-7 has excellent selectivity for the recognition of the metastatic PCa cells. Clinical tissue imaging further confirmed these results. Therefore, both high binding affinity and specificity to metastatic PCa cells and tissues afford DML-7 with the potential for development into a novel tool for diagnosis and targeted drug delivery against metastatic prostate cancer.
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