Precise delivery of medical gases by engineered nanomedicine for enhanced liver fibrosis therapy.

Liver fibrosis, a significant global health issue, results from sustained liver injury and is characterized by progressive damage to the liver. Treating liver fibrosis poses considerable challenges due to difficulty in reversal and frequent association with complex, chronic liver injuries. Recently, medical gas therapies have emerged as a promising novel approach for addressing liver fibrosis. The primary gases involved include carbon monoxide (CO), hydrogen (H2), nitric oxide (NO), hydrogen sulfide (H2S), sulfur dioxide (SO2), and oxygen (O2). Several gases exist as endogenous gasotransmitters, thereby inherently capable of participating in known cellular signaling pathways that can be exploited for therapeutic purposes. The principal therapeutic advantages of these gases revolve around the attenuation of key features of liver fibrosis. They exert antioxidant and anti-inflammatory effects, inhibit hepatic stellate cell (HSC) activation and cytokine production, neutralize reactive oxygen species (ROS), and prevent hepatocyte apoptosis. Leveraging on the unique, attractive properties of medical gases, this review examines current scientific findings and investigates the use of advanced delivery modalities, including molecular donors and nanotechnology-based systems, to enhance the specificity of gas therapy for liver fibrosis.