STING signaling in liver diseases and the therapeutic potential of nanodrug delivery systems

As a key player in cytosolic DNA surveillance, the stimulator of interferon genes (STING) pathway orchestrates both innate and adaptive immunity, predominantly via type I interferon (IFN-I) induction. Within the liver, STING activity is elevated in nonparenchymal cells, where it critically regulates immune homeostasis. Recent studies have increasingly revealed the versatile regulatory functions of the STING pathway throughout diverse liver disease progression, including viral hepatitis, metabolic dysfunction-associated steatotic liver disease, alcohol-induced hepatotoxicity, liver fibrosis, immune-mediated hepatic disorders, and hepatocellular carcinoma. Concurrently, advancements in nanodrug delivery systems (NDDSs) have revolutionized targeted therapy due to the reinforced stability, precise targeting ability, and enhanced permeability and retention. This review synthesizes current knowledge on the mechanistic interplay between the STING signaling and liver diseases and explores the ability of NDDS-based strategies to facilitate immunomodulation and improve outcomes.