PDA@Pt nanoparticles: Dual antiviral and anti-inflammatory effects against influenza A virus through multi-target mechanisms.

Influenza A virus (IAV) infection can lead to severe complications, including acute lung injury, driven by hypoxia, excessive reactive oxygen species (ROS), and cytokine release syndrome (CRS). To address the limitations of current therapies, such as insufficient antiviral efficacy and poor CRS control, we developed polydopamine-platinum core-shell nanoparticles (PDA@Pt) with dual antiviral and anti-inflammatory functions. The PDA core scavenges ROS to alleviate CRS and disrupts viral replication, while the Pt shell inhibits viral entry and catalyzes the decomposition of H2O2 into O2 to relieve hypoxia. PDA@Pt demonstrated excellent biocompatibility and potent antiviral activity by suppressing viral replication through dual mechanisms: inhibition of clathrin-mediated endocytosis via downregulation of clathrin heavy chain and dynamin, and multimodal therapeutic effects via ROS scavenging, O2 generation, and suppression of proinflammatory cytokines. Furthermore, PDA@Pt modulated key signaling pathways, including JAK/STAT and NF-κB, highlighting its broad-spectrum potential against viral infections and associated inflammatory complications.