BODIPY-Based Ratiometric Fluorescent Probe for Sensing Peroxynitrite in Inflammatory Cells and Tissues

Biosensors (Basel). 2024 Dec 22;14(12):638. doi: 10.3390/bios14120638.

Abstract

Peroxynitrite (ONOO-) plays an important role in many physiological and pathological processes. Excessive ONOO- in cells leads to oxidative stress and inflammation. However, precise monitoring of ONOO- levels in specific organelles (e.g., mitochondria) is still lacking and urgently needed. Herein, we rationally designed a mitochondria-targeted ratiometric fluorescent probe, MOBDP-I, for imaging of ONOO- in the mitochondria of inflammatory cells and model mice. This probe, MOBDP-I, was synthesized by conjugating a BODIPY fluorophore to a mitochondria-targeting moiety-indole-salt group by a carbon-carbon double bond (C=C). In the presence of ONOO-, the C=C bond between the BODIPY backbone and the indole-salt group was oxidized and broken, leading to an 18-fold enhancement of fluorescence at 510 nm, along with a significant fluorescence decrease at 596 nm. The ratiometric response property bestowed the probe with advantages in the precise quantification of ONOO- in cells, thus allowing estimation of the extent of inflammation in living cells and mouse models of rheumatoid arthritis, peritonitis, and brain inflammation. MOBDP-I could act as an effective molecular tool to study the relationship between ONOO- and the occurrence and development of inflammatory diseases.

Keywords: fluorescence imaging; inflammatory; peroxynitrite; ratiometric probe.

MeSH terms

  • Animals
  • Biosensing Techniques
  • Boron Compounds* / chemistry
  • Fluorescent Dyes*
  • Humans
  • Inflammation*
  • Mice
  • Mitochondria / metabolism
  • Peroxynitrous Acid* / analysis

Substances

  • Fluorescent Dyes
  • Peroxynitrous Acid
  • Boron Compounds
  • 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene