PtCu-bimetallic modified MOF nanozyme composites for alleviating acute liver injury via reactive oxygen species elimination and inflammation regulation.

作者：Yuying Cai, Lin-Jiao Yang, Mengmeng Pan, Nefise Nurtay, Yan Yu, Min-Jie Xie, Ming Jiang, Yao Wang, Xu Yu, Li Xu · 发表于：Journal of Controlled Release · 年份：2026 · DOI：10.1016/j.jconrel.2026.114774 · 被引用次数：8 · 研究领域：Medicine

Excessive reactive oxygen species (ROS) accumulation and dysregulated inflammation drive acetaminophen (APAP)-induced acute liver injury (ALI), yet the therapeutic effect of the commonly used clinical drug N-acetylcysteine (NAC) still has certain limitations at present. Here, we engineered a multifunctional nanozyme nanocomposite, MPCNH, by in situ deposition of bimetallic PtCu nanoparticles onto UiO-66 metal-organic frameworks (MOFs), loading NAC, and coating with hyaluronic acid (HA) to enhance biocompatibility. MPCNH exhibited cascade superoxide dismutase (SOD)-like and catalase (CAT)-like catalytic activities, enabling rapid ROS clearance and mitochondrial protection in APAP-challenged hepatocytes. Meanwhile, the delivery of the therapeutic drug NAC was achieved. In vivo, MPCNH lowered serum transaminases, activated the Keap1-Nrf2 antioxidant pathway, shifted macrophages polarization toward an anti-inflammatory M2 phenotype and restored metabolic balance. By integrating catalytic and pharmacological functions, MPCNH offers a synergistic strategy to simultaneously eliminate oxidative stress and regulate inflammation, providing a promising therapeutic platform for oxidative stress-driven liver injury.