H₂ can be delivered via nanocarriers or nanogenerators to achieve targeted accumulation at disease sites, significantly improving therapeutic effects compared to systemic H₂ administration
How Does It Work?
Three key mechanisms: Antioxidant (scavenging •OH and ONOO⁻), Anti-inflammatory (down-regulating IL-1β, IL-6, TNF-α), Anti-neoplastic (activating apoptosis via AMPK pathway)
Why Does It Matter?
Overcomes limitations of conventional H₂ therapy (poor targeting, low utilization) and enables synergistic effects with photothermal therapy, chemotherapy, and radiotherapy
Key Mechanisms: How H₂ Works
Mechanism
Action
Pathways Involved
Antioxidant
Selectively scavenges •OH, ONOO⁻
Nrf2, ERK1/2, JNK, Ca²⁺ signaling
Anti-inflammatory
Down-regulates cytokines
NF-κB, HMGB-1, TLR4
Anti-neoplastic
Enhances cancer cell apoptosis
AMPK, caspase-3, AIF
Selectivity is key: H₂ only reduces toxic ROS while preserving signaling ROS
Nanomaterial Strategies
H₂ Carriers
Microbubbles, Mg@p-SiO₂, mesoporous silica
Enable controlled release via stimuli (pH, light, ultrasound)
H₂ Generators
PdH₀.₂ nanocrystals, liposomal nanoreactors
Produce H₂ in situ at tumor sites via photocatalysis
Advantages
Passive targeting via EPR effect
Active targeting through surface modification
Sustained H₂ release at therapeutic concentrations
Conclusion
Combining H₂ therapy with nanomaterials represents a paradigm shift from systemic to precision gas therapy. This approach enables targeted delivery, controlled release, and synergistic effects with conventional treatments, opening new avenues for cancer therapy and inflammatory disease management.