An APE1 gated signal amplified biosensor driven by catalytic hairpin assembly for the specific imaging of microRNA in situ

Int J Biol Macromol. 2024 Mar;262(Pt 1):129902. doi: 10.1016/j.ijbiomac.2024.129902. Epub 2024 Feb 1.

Abstract

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

Keywords: AND-gate; APE1; CHA; DNA tetrahedron; In situ imaging; microRNA.

MeSH terms

  • Animals
  • Biosensing Techniques* / methods
  • Catalysis
  • Endonucleases
  • Mice
  • MicroRNAs* / genetics
  • Neoplasms*

Substances

  • MicroRNAs
  • Endonucleases