An Activatable and Switchable Nanoaggregate Probe for Detecting H₂ S and Its Application in Mice Brains

Area of Science:

• Chemical Biology
• Molecular Imaging
• Mitochondrial Research

Background:

• Hydrogen sulfide (H₂S) is a crucial signaling molecule involved in various physiological processes.
• Tracking endogenous H₂S in biological systems, especially within mitochondria, remains challenging.
• Developing advanced probes is essential for understanding H₂S-related biological functions.

Purpose of the Study:

• To design and synthesize a novel, switchable, dual-mode nanoprobe (HSDPP) for detecting hydrogen sulfide (H₂S).
• To investigate the probe's capability in imaging both exogenous and endogenous H₂S in living cells.
• To apply the nanoprobe for tracking mitochondrial H₂S dynamics in vivo, particularly in response to specific stimuli.

Main Methods:

• Sequential activation probe design method.
• Synthesis and characterization of the HSDPP nanoprobe.
• In vitro and in vivo imaging of H₂S using fluorescence microscopy.
• Application in tracking endogenous H₂S upregulation in mice brains stimulated by S-adenosyl-L-methionine (SAM).

Main Results:

• The HSDPP nanoprobe exhibits sequential activation, initially forming H-type aggregates with green emission upon H₂S detection.
• The probe subsequently binds to mtDNA, switching emission from green to deep-red, allowing dual-mode imaging.
• Successfully imaged exogenous and endogenous H₂S in living cells.
• Demonstrated in vivo tracking of H₂S upregulation in mice brains, correlating with SAM stimulation.
• The probe possesses an optimal partition coefficient (LogP=1.269) for biological applications.

Conclusions:

• HSDPP is an effective tool for imaging exogenous and endogenous H₂S in vitro and in vivo.
• The study presents a novel design strategy for switchable chemosensors targeting biomolecules and mitochondrial DNA.
• This research provides valuable insights into H₂S signaling pathways and mitochondrial function.