A Non-G-Quadruplex DNA Aptamer Targeting NCL for Diagnosis and Therapy in Bladder Cancer,Advanced Healthcare Materials

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A Non-G-Quadruplex DNA Aptamer Targeting NCL for Diagnosis and Therapy in Bladder Cancer
Advanced Healthcare Materials ( IF 10.0 ) Pub Date : 2023-06-01 , DOI: 10.1002/adhm.202300791
Yunyi Liu ₁ , Bei Hu ₁ , Xiaming Pei ₂ , Juan Li ₁ , Dan Qi ₃ , Yuxi Xu ₁ , Hailong Ou ₁ , Yatao Wu ₁ , Lei Xue ₄ , Jason H Huang _{3,

5} , Erxi Wu _{3,

5,

6,

7} , Xiaoxiao Hu _{1,

8,

9,

10}

Affiliation

State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Biology, Molecular Science and Biomedicine Laboratory and Aptamer Engineering Center of Hunan Province, Hunan University, Changsha, Hunan, 410082, China.
Department of Urology, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine. Changsha, Hunan, 410013, China.
Department of Neurosurgery and Neuroscience Institute, Baylor Scott & White Health, Temple, TX, 76508, USA.
Department of Pathology, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine. Changsha, Hunan, 410013, China.
Department of Medical Education, Texas A&M University School of Medicine, College Station, TX, 77843, USA.
Department of Pharmaceutical Sciences, Texas A&M University School of Pharmacy, College Station, TX, 77843, USA.
LIVESTRONG Cancer Institutes and Department of Oncology, Dell Medical School, The University of Texas at Austin, Austin, TX, 78712, USA.
Research Institute of Hunan University in Chongqing, Chongqing, 401120, China.
Shenzhen Research Institute, Hunan University, Shenzhen, Guangdong, 518000, China.
Hunan Yonghe-sun Biotechnology Co. Ltd., Changsha, Hunan, 410082, China.

Bladder cancer (BC) is a highly aggressive malignant tumor affecting the urinary system, characterized by metastasis and a poor prognosis that often leads to limited therapeutic success. This study aims to develop a novel DNA aptamer for the diagnosis and treatment of BC using a tissue-based systematic evolution of ligands by an exponential enrichment (SALEX) process. By using SELEX, this work successfully generates a new aptamer named TB-5, which demonstrates a remarkable and specific affinity for nucleolin (NCL) in BC tissues and displays marked biocompatibility both in vitro and in vivo. Additionally, this work shows that NCL is a reliable tissue-specific biomarker in BC. Moreover, according to circular dichroism spectroscopy, TB-5 forms a non-G-quadruplex structure, distinguishing it from the current NCL–targeting aptamer AS1411, and exhibits a distinct binding region on NCL compared to AS1411. Notably, this study further reveals that TB-5 activates NCL function by promoting autophagy and suppressing the migration and invasion of BC cells, which occurs by disrupting mRNA transcription processes. These findings highlight the critical role of NCL in the pathological examination of BC and warrant more comprehensive investigations on anti-NCL aptamers in BC imaging and treatment.

中文翻译：

靶向 NCL 的非 G 四链体 DNA 适配子用于膀胱癌的诊断和治疗

膀胱癌（BC）是一种影响泌尿系统的高度侵袭性恶性肿瘤，其特征是转移和不良预后，通常会导致有限的治疗成功。本研究旨在通过指数富集（SALEX）过程使用基于组织的配体系统进化来开发一种新型 DNA 适配体，用于诊断和治疗 BC。通过使用 SELEX，这项工作成功生成了一种名为 TB-5 的新型适配体，它对 BC 组织中的核仁素（NCL）表现出显着的特异性亲和力，并在体外和体内表现出显着的生物相容性。此外，这项工作表明 NCL 是 BC 中可靠的组织特异性生物标志物。此外，根据圆二色谱光谱，TB-5 形成非 G 四链体结构，区别于目前靶向 NCL 的适配体 AS1411，并且与 AS1411 相比，在 NCL 上表现出独特的结合区。值得注意的是，这项研究进一步揭示了 TB-5 通过促进自噬和抑制 BC 细胞的迁移和侵袭来激活 NCL 功能，这是通过破坏 mRNA 转录过程来实现的。这些发现强调了 NCL 在 BC 病理检查中的关键作用，并需要对 BC 成像和治疗中的抗 NCL 适配体进行更全面的研究。

更新日期：2023-06-01

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