Mitochondrial H₂S_n-Mediated Anti-Inflammatory Theranostics.

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Pharmacology

Background:

• Non-steroidal anti-inflammatory drugs (NSAIDs) demand improved delivery systems to minimize side effects.
• Inflammation site biomarkers, like hydrogen polysulfide (H2Sn), offer targets for responsive drug delivery.
• Theranostics combine diagnosis and therapy, presenting a promising avenue for advanced anti-inflammatory treatments.

Purpose of the Study:

• To develop a novel theranostic agent (TA1) for targeted anti-inflammatory drug delivery.
• To design a system responsive to hydrogen polysulfide (H2Sn) for selective drug release at inflammation sites.
• To evaluate the therapeutic and diagnostic capabilities of TA1 in vitro and in vivo.

Main Methods:

• Synthesis of a theranostic agent (TA1) comprising an H2Sn-responsive trigger, a mitochondria-targeting fluorophore (Rhodol-TPP), and indomethacin.
• In vitro studies using inflammation-induced cells to assess TA1's response to H2Sn and its localization.
• In vivo experiments with inflammation-induced mouse models to evaluate drug release, therapeutic efficacy, and diagnostic potential.

Main Results:

• TA1 selectively reacted with H2Sn, releasing Rhodol-TPP and indomethacin.
• Confocal microscopy confirmed TA1 localization in mitochondria of inflammation-induced cells.
• TA1 suppressed COX-2 and prostaglandin E2 levels in vitro and in vivo, demonstrating therapeutic effects and inflammation-site-selective drug release.

Conclusions:

• The developed theranostic agent TA1 effectively targets inflammation sites and releases drugs in response to H2Sn.
• TA1 demonstrates significant anti-inflammatory therapeutic effects and diagnostic capabilities in preclinical models.
• This H2Sn-responsive theranostic approach holds high applicability for treating inflammatory diseases.