An APE1 gated signal amplified biosensor driven by catalytic hairpin assembly for the specific imaging of microRNA in situ,International Journal of Biological Macromolecules

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An APE1 gated signal amplified biosensor driven by catalytic hairpin assembly for the specific imaging of microRNA in situ
International Journal of Biological Macromolecules ( IF 7.7 ) Pub Date : 2024-02-01 , DOI: 10.1016/j.ijbiomac.2024.129902
Mengxin Zhang ₁ , Yingyu Zhang ₂ , Qionglin Wang ₃ , Kangbo Liu ₄ , Lifeng Li ₁ , Zhidan Yu ₁ , Ligong Hou ₅ , Xianwei Zhang ₁ , Huan Zhao ₆ , Weyland Cheng ₃ , Wancun Zhang ₇

Affiliation

Health Commission of Henan Province Key Laboratory for Precision Diagnosis and Treatment of Pediatric Tumor, Children's Hospital Affiliated to Zhengzhou University, Zhengzhou 450018, China.
Henan Key Laboratory of Rare Diseases, Endocrinology and Metabolism Center, The First Affiliated Hospital, College of Clinical Medicine of Henan University of Science and Technology, Luoyang 471003, China.
Health Commission of Henan Province Key Laboratory for Precision Diagnosis and Treatment of Pediatric Tumor, Children's Hospital Affiliated to Zhengzhou University, Zhengzhou 450018, China; Henan Key Laboratory of Children's Genetics and Metabolic Diseases, Children's Hospital Affiliated to Zhengzhou University, Zhengzhou 450018, China.
Henan Medical Equipment Inspection Institute, Zhengzhou 450018, China.
Henan International Joint Laboratory for Prevention and Treatment of Pediatric Disease, Children's Hospital Affiliated to Zhengzhou University, Zhengzhou 450018, China.
Department of oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450018, China.
Health Commission of Henan Province Key Laboratory for Precision Diagnosis and Treatment of Pediatric Tumor, Children's Hospital Affiliated to Zhengzhou University, Zhengzhou 450018, China; Henan International Joint Laboratory for Prevention and Treatment of Pediatric Disease, Children's Hospital Affiliated to Zhengzhou University, Zhengzhou 450018, China; Henan Key Laboratory of Children's Genetics and Metabolic Diseases, Children's Hospital Affiliated to Zhengzhou University, Zhengzhou 450018, China.

imaging of microRNA (miRNA) content and distribution is valuable for monitoring tumor progression. However, tumor specific imaging remains a challenge due to low miRNA abundance, lack of biological compatibility, and poor specificity. In this study, we designed a DNA tetrahedral framework complex with hairpins (DTF-HP) consisting of an apurinic/apyrimidinic site (AP site) that could be specifically recognized and cleaved by apurinic/apyrimidinic endonuclease 1 (APE1). Efficient and specific imaging of miR-21 in tumors was thus achieved through catalytic hairpin assembly (CHA) reaction. In this study, DTF-HP was successfully constructed to trigger the cumulative amplification of fluorescence signal . The specificity, sensitivity and serum stability of DTF-HP were verified , and DTF-HP could be easily taken up by cells, acting as a biosensor to detect tumors in mice. Furthermore, we verified the ability of DTF-HP to specifically image miR-21 in tumors, and demonstrated its capability for tumor-specific imaging in clinical samples.

中文翻译：

由催化发夹组装驱动的 APE1 门控信号放大生物传感器，用于 microRNA 原位特异性成像

microRNA (miRNA) 含量和分布的成像对于监测肿瘤进展很有价值。然而，由于 miRNA 丰度低、缺乏生物相容性和特异性差，肿瘤特异性成像仍然是一个挑战。在这项研究中，我们设计了一种带有发夹的DNA四面体框架复合物（DTF-HP），其由脱嘌呤/脱嘧啶位点（AP位点）组成，可以被脱嘌呤/脱嘧啶核酸内切酶1（APE1）特异性识别和切割。因此，通过催化发夹组装（CHA）反应实现了肿瘤中miR-21的高效和特异性成像。本研究成功构建了DTF-HP来触发荧光信号的累积放大。验证了DTF-HP的特异性、敏感性和血清稳定性，并且DTF-HP易于被细胞摄取，可作为检测小鼠肿瘤的生物传感器。此外，我们验证了DTF-HP对肿瘤中miR-21进行特异性成像的能力，并展示了其在临床样本中进行肿瘤特异性成像的能力。

更新日期：2024-02-01

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