Self-Assembly of DNA Nanoflares in Mitochondria for Sensitive In Situ Imaging of Cancer Markers

ACS Nano. 2025 Jun 3;19(21):19918-19926. doi: 10.1021/acsnano.5c02952. Epub 2025 May 21.

Abstract

Real-time monitoring of cancer markers at the organelle level offers an effective approach to understanding the mechanisms of cancer generation. Herein, we have developed a sensitive in situ imaging method for human apurinic/apyrimidinic endonuclease 1 (APE1), a cancer biomarker that regulates mitochondrial function by triggering a chain reaction within mitochondria to form highly efficient DNA nanoflares through palindrome-driven assembly (PDA). To deliver the DNA sequences with palindromes for the chain reaction, we prepared triphenylphosphine (TPP)-modified polymeric nanoparticles specifically targeting mitochondria. The presence of APE1 in mitochondria triggered the PDA, leading to the in situ assembly of DNA nanoflares and yielding highly sensitive imaging of APE1. This strategy demonstrates the high capability of combined chain reactions for the real-time monitoring of cancer markers within organelles.

Keywords: APE1; DNA nanoflare; chain reaction; mitochondria; self-assembly; sensitive imaging.

MeSH terms

  • Biomarkers, Tumor* / analysis
  • Biomarkers, Tumor* / metabolism
  • DNA* / chemistry
  • DNA* / metabolism
  • DNA-(Apurinic or Apyrimidinic Site) Lyase* / analysis
  • DNA-(Apurinic or Apyrimidinic Site) Lyase* / metabolism
  • HeLa Cells
  • Humans
  • Mitochondria* / metabolism
  • Nanoparticles* / chemistry
  • Organophosphorus Compounds / chemistry

Substances

  • DNA
  • Biomarkers, Tumor
  • DNA-(Apurinic or Apyrimidinic Site) Lyase
  • APEX1 protein, human
  • triphenylphosphine
  • Organophosphorus Compounds