PtCu-bimetallic modified MOF nanozyme composites for alleviating acute liver injury via reactive oxygen species elimination and inflammation regulation.
Cai Yu-Ying, Yang Lin-Jiao, Pan Meng-Meng, Nurtay Nefise, Yu Yan-Ping, Xie Minjie, Jiang Ming, Wang Yao, Yu Xu, Xu Li
Abstract
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.
Key Findings
- MPCNH nanozyme composite exhibits cascade SOD-like and CAT-like catalytic activities for rapid ROS clearance and mitochondrial protection in hepatocytes.
- MPCNH activates the Keap1-Nrf2 antioxidant pathway in vivo, reducing serum transaminases and alleviating acute liver injury.
- MPCNH shifts macrophage polarization toward an anti-inflammatory M2 phenotype and restores metabolic balance, combining catalytic and pharmacological functions.
Clinical Significance
The MPCNH nanozyme composite offers a promising therapeutic platform for treating oxidative stress-driven acute liver injury by simultaneously eliminating ROS and regulating inflammation, potentially improving outcomes beyond current treatments like N-acetylcysteine.
Citation
Cai Yu-Ying, Yang Lin-Jiao, Pan Meng-Menget al.. PtCu-bimetallic modified MOF nanozyme composites for alleviating acute liver injury via reactive oxygen species elimination and inflammation regulation. Journal of controlled release : official journal of the Controlled Release Society. 2026-May-10.