A dual-pronged strategy: multi-bioactive nanoplatform synergizes ROS antidote and iron stabilization to protect against liver ischemia-reperfusion injury

, together synergistically alleviating LIRI. Se@MelP possessed excellent ROS scavenging activity, strong iron chelating capability, and favorable biosafety. In vitro experiments confirmed that Se@MelP effectively eliminated excessive ROS, alleviated Fe²⁺ overload, and mitigated mitochondrial damage, protecting cells from oxidative stress and ferroptosis. Upon intravenous administration in the LIRI model, Se@MelP markedly improved liver function, attenuated tissue injury, and mitigated oxidative stress, inflammatory responses, and ferroptosis. Notably, Se@MelP activated the AMPK/Nrf2 pathway, enhancing the endogenous antioxidant defenses and anti-ferroptotic capacity, thereby conferring protection against liver injury. This multi-bioactive nanoplatform offers a promising therapeutic strategy for LIRI and other oxidative stress‑related liver diseases.