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Delivery of Molecular Hydrogen for Precision Immunomodulation: Mechanisms, Detection Methods, and Applications

Gangfeng Li, Hannan Cui, Ruixiao Fan, Guming Liu, Zishuo Hou, Yibo Zhang, Xuanming Che, Tengjiao Wang, Hongbo Wei, Peng Li

Advanced Science · 2025 · 12(32) · e00283

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Abstract

The delivery of molecular hydrogen (H2) is increasingly recognized for its potential in precision immunomodulation, primarily through multiple pathways such as antioxidant action, modulation of inflammatory factors, and inhibition of apoptosis. These effects contribute to a balanced and functional immune system, highlighting the therapeutic promise of H2 in various inflammatory conditions. However, two critical issues remain unresolved: the unclear mechanism underlying the immunomodulatory effects of H2 and the lack of precision detection methods to clarify the dose-efficacy relationship in vivo. Since previous reviews focused on developing nanomaterials for H2 delivery, they often overlook analyses of the immunomodulation mechanisms and fail to update the detection methods. To address these gaps, a review that explores the immunomodulatory mechanisms of H2 is proposed, the recent detection methods, and the classification and applications of advanced H2 delivery systems, aiming to enhance the understanding of precision immunomodulation strategies leveraging their properties.

Study details

Article type
Review
Disease / injury model
Inflammatory diseases (arthritis, chronic wounds, cardiovascular injury, tumors, bacterial infections, liver diseases)
Dose comparison
The review discusses the importance of dose-efficacy relationships, challenges in achieving sustained therapeutic concentrations, and the need for precision detection methods to clarify dose-response in vivo.
Dose-dependent effect
Yes
Outcome
Mixed
Findings
This review highlights the therapeutic promise of molecular hydrogen (H2) in precision immunomodulation, details its mechanisms (antioxidant, anti-inflammatory, anti-apoptotic), noting H2 modulates the expression of inflammatory genes and proteins via signaling pathways like NF-κB, MAPK, and Nrf2/HO-1. The review also discusses advanced delivery and detection methods, and summarizes applications in various diseases It emphasizes the need for improved delivery systems, real-time monitoring, and mechanistic understanding for clinical translation.

Classification

Organs & Tissues
Physiological Systems
Countries
Also
Methods of Administration ComparedDose/Concentration ComparedDrug/Therapy/Supplement ComparedPharmacokinetics Discussed