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

Molecular Therapy. Nucleic Acids
Hui ZhangWeihong Tan

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 ...Continue Reading

Citations

Jan 1, 2019·Journal of Drug Targeting·Ge GaoJuewen Liu
Apr 4, 2021·Biomedicines·Fernando Cartón-GarcíaFernando Pastor
Jun 8, 2021·Frontiers in Cell and Developmental Biology·Zheng LiChao Liang
Jun 12, 2019·Journal of the American Chemical Society·Xiaoqiu WuWeihong Tan
Dec 21, 2021·ACS Applied Materials & Interfaces·Hui ZhangWeihong Tan

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Methods Mentioned

BETA
surgical resection
SELEX
PCR
xenograft
flow cytometry
confocal microscopy
flow
Fluorescence
Fluorescence Imaging

Software Mentioned

GraphPad Prism
Nupack

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