ROS-responsive hydrogel nanoarmor enables stepwise photodynamic viral inactivation and sustained anti-inflammation for monkeypox therapy.

Currently, monkeypox virus (MPXV) treatment methods face a dilemma of potential drug resistance. They cannot simultaneously address two core pathological mechanisms driving infection: continuous viral replication and uncontrolled inflammatory storm. To overcome these challenges, we innovatively developed a dual-function therapeutic strategy with precise virus clearance and anti-inflammatory effects, constructing a dual hydrogel system synergistically combining phototherapy and immunomodulatory effects. Specifically, aggregation-induced emission (AIE) nanoparticles (NPs) are embedded in a reactive oxygen species (ROS)-degradable polyvinyl alcohol (PVA)-N1-(4-borobenzoyl)-N3-(4-borobenzoyl)-the N1, the N1, N3, N3-tetramethylpropane-1,3-diamine (tsPBA) hydrogel, while the anti-inflammatory agent is loaded in a zwitterionic hydrogel (SBMA) matrix. Under near-infrared band laser irradiation, AIE NPs efficiently generate large amounts of ROS, which, together with inflammation-produced endogenous ROS, trigger the rapid degradation of the ROS-responsive hydrogel and release of AIE NPs. The generated ROS effectively destroys the MPXV shell and strongly inactivates the virus. After virus clearance, the SBMA hydrogel continuously releases anti-inflammatory drugs (Dexamethasone, DXMS) to inhibit excessive pro-inflammatory cytokines and reduce inflammation-induced tissue damage. In mouse, rabbit, and non-human primate models with MPXV-induced skin damage, this hydrogel nanoparticle protective layer significantly inhibits viral replication and accelerates wound healing, representing a transformative, convertible platform for treating MPXV and other highly inflammatory viral infections.