Molecular Recognition and In-Vitro-Targeted Inhibition of Renal Cell Carcinoma Using a DNA Aptamer

Hui Zhang; Zhibo Wang; Lin Xie; Yibin Zhang; Tanggang Deng; Jianglin Li; Jing Liu; Wei Xiong; Lei Zhang; Lin Zhang; Bo Peng; Leye He; Mao Ye; Xiaoxiao Hu; Weihong Tan

doi:10.1016/j.omtn.2018.07.015

Molecular Recognition and In-Vitro-Targeted Inhibition of Renal Cell Carcinoma Using a DNA Aptamer

Mol Ther Nucleic Acids. 2018 Sep 7:12:758-768. doi: 10.1016/j.omtn.2018.07.015. Epub 2018 Aug 4.

Authors

Hui Zhang¹, Zhibo Wang¹, Lin Xie¹, Yibin Zhang¹, Tanggang Deng¹, Jianglin Li¹, Jing Liu², Wei Xiong³, Lei Zhang⁴, Lin Zhang¹, Bo Peng¹, Leye He⁵, Mao Ye⁶, Xiaoxiao Hu⁷, Weihong Tan⁸

Affiliations

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 410082, China.
² Molecular Biology Research Center, School of Life Sciences, Central South University, Changsha, Hunan 410078, China.
³ Ophthalmology and Eye Research Center, the Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China.
⁴ Department of Nephrology, the Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China.
⁵ Department of Urology, the Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, China.
⁶ 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 410082, China. Electronic address: goldleaf@hnu.edu.cn.
⁷ 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 410082, China. Electronic address: xxhu@hnu.edu.cn.
⁸ 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 410082, China. Electronic address: tan@chem.ufl.edu.

Abstract

Renal cell carcinoma (RCC) is the most common malignant tumor of the urinary system, and it has a high frequency of local invasion and distant metastasis. Although multiple advances have been made in the diagnosis and therapy of RCC, the vast majority of patients with metastatic RCC remain incurable. In this study, an aptamer named SW-4 against RCC 786-O cells was identified from a known sequence pool. The identified aptamer exhibited high binding affinity for target cells with dissociation constants in the nanomolar range. Binding analysis revealed that SW-4 only bound to RCC 786-O cells, but not HEK293T cells or human proximal tubular HK-2 cells, indicating that SW-4 has excellent binding selectivity. By sequence optimization, the 26-nt truncated SW-4b demonstrated improved binding affinity, and it was internalized into target cells via caveolae-mediated endocytosis in a temperature-dependent manner. Furthermore, fluorescence imaging confirmed that SW-4b accumulated at tumor sites in 786-O xenograft nude mice models and specifically recognized clinical RCC tissues. Meanwhile, SW-4b inhibited proliferation of 786-O cells by arresting cell cycle progression at the S phase. Taken together, these results indicate that SW-4b is a potential candidate for development into a novel tool for diagnosis and targeted therapy of RCC.

Keywords: aptamer; binding affinity; internalization; proliferation; renal cell carcinoma.