Dual-Modality Accurate Visualization of Drug Synergy Based on Mass Spectrometry and Fluorescence Imaging

Area of Science:

• Biomedical Engineering
• Pharmacology
• Analytical Chemistry

Background:

• The synergistic potential between nonsteroidal anti-inflammatory drugs (NSAIDs) and hydrogen sulfide (H2S) is recognized, but direct evidence and effective visualization methods are lacking.
• Accurate confirmation of synergistic effects is challenging with single fluorescence detection methods.
• Gastric mucosal damage is a common side effect associated with NSAID use.

Purpose of the Study:

• To develop an integrated diagnostic and therapeutic fluorescent probe for visualizing drug synergy.
• To quantitatively assess the release of H2S from the developed probe.
• To confirm the synergistic anti-inflammatory and protective effects of naproxen and H2S in cellular and animal models.

Main Methods:

• Synthesis of a novel integrated fluorescent probe, Nap-NP-NSB, by conjugating naproxen with a self-immolative spacer, enabling H2S release.
• In vitro and cellular evaluation of H2S quantitative release and assessment of synergistic effects on inflammation and oxidative damage in gastric mucosa cells.
• In vivo dual-modal imaging using fluorescence and mass spectrometry imaging in a mouse model of acute hepatitis to visualize drug synergy in liver and stomach tissues.

Main Results:

• The Nap-NP-NSB probe successfully released H2S quantitatively in vitro and in cells.
• The synergistic effect of H2S and naproxen was confirmed, demonstrating enhanced anti-inflammatory activity and reduced gastric mucosal damage.
• Dual-modal imaging provided accurate visualization of the drug synergistic effect and confirmed improved therapeutic outcomes.

Conclusions:

• The developed Nap-NP-NSB probe offers a dual visualization method combining fluorescence and mass spectrometry imaging for studying drug synergies.
• This approach provides a new strategy for investigating the synergistic effects of NSAIDs and H2S, leading to improved therapeutic strategies.
• The findings highlight the potential for developing targeted therapies with reduced side effects, particularly for gastric protection.