Light-Driven Mitochondrion-to-Nucleus DNA Cascade Fluorescence Imaging and Enhanced Cancer Cell Photoablation

J Am Chem Soc. 2024 May 15;146(19):12941-12949. doi: 10.1021/jacs.3c13095. Epub 2024 Apr 29.

Abstract

Nucleic acids are mainly found in the mitochondria and nuclei of cells. Detecting nucleic acids in the mitochondrion and nucleus in cascade mode is crucial for understanding diverse biological processes. This study introduces a novel nucleic acid-based fluorescent styrene dye (SPP) that exhibits light-driven cascade migration from the mitochondrion to the nucleus. By introducing N-arylpyridine on one side of the styrene dye skeleton and a bis(2-ethylsulfanyl-ethy)-amino unit on the other side, we found that SPP exhibits excellent DNA specificity (16-fold, FDNA/Ffree) and a stronger binding force to nuclear DNA (-5.09 kcal/mol) than to mitochondrial DNA (-2.59 kcal/mol). SPP initially accumulates in the mitochondrion and then migrates to the nucleus within 10 s under light irradiation. By tracking the damage to nucleic acids in apoptotic cells, SPP allows the successful visualization of the differences between apoptosis and ferroptosis. Finally, a triphenylamine segment with photodynamic effects was incorporated into SPP to form a photosensitizer (MTPA-SPP), which targets the mitochondria for photosensitization and then migrates to the nucleus under light irradiation for enhanced photodynamic cancer cell treatment. This innovative nucleic acid-based fluorescent molecule with light-triggered mitochondrion-to-nucleus migration ability provides a feasible approach for the in situ identification of nucleic acids, monitoring of subcellular physiological events, and efficient photodynamic therapy.

MeSH terms

  • Apoptosis / drug effects
  • Cell Line, Tumor
  • Cell Nucleus* / chemistry
  • Cell Nucleus* / metabolism
  • DNA / chemistry
  • Fluorescent Dyes* / chemical synthesis
  • Fluorescent Dyes* / chemistry
  • HeLa Cells
  • Humans
  • Light*
  • Mitochondria* / chemistry
  • Mitochondria* / drug effects
  • Mitochondria* / metabolism
  • Neoplasms / diagnostic imaging
  • Optical Imaging*
  • Photochemotherapy
  • Photosensitizing Agents / chemistry
  • Photosensitizing Agents / pharmacology