Curcumin-copper complex nanoparticles as antioxidant nanozymes for acute kidney injury alleviation
Xinyu Huang, Fengxian Zhang, Yuan Yang, Jiawei Liu, Xiangyun Tan, Peng Zhou, Xiaolei Tang, Junjie Hu, Liang Chen, Ming Yuan, Guohua Zheng, Ziqiang Xu, Zhenpeng Qiu
Abstract
Acute kidney injury (AKI) is a heterogeneous disorder frequently occurring in hospitalized patients with multiple comorbidities. Chemotherapy-associated AKI (e.g., cisplatin-induced AKI, CP-AKI) and rhabdomyolysis-induced AKI (RM-AKI) are initiated by the excessive accumulation of reactive oxygen species (ROS). Herein, metal phenolic networks (MPNs) composed of copper (II) (Cu 2+ ), a typical cofactor in the native superoxide dismutase (SOD), and a well-studied natural antioxidant curcumin (Cur) (denoted as Cur-Cu) were fabricated to integrate the ROS-scavenging properties of metal ions and polyphenols. The results indicate that Cur-Cu nanoparticles (NPs) possessed robust antioxidative enzyme-like activities. Meanwhile, Cur-Cu NPs with polyethylene glycol (PEG) covalent modification (Cur-Cu@PEG) abolished the ROS-triggered oxidative damage of HK-2 cells. Moreover, Cur-Cu@PEG displayed acceptable biocompatibility in vivo . Furthermore, Cur-Cu@PEG alleviated CP-AKI and RM-AKI in mice with kidney-targeted delivery. Mechanistically, Cur-Cu@PEG effectively lessened the production of ROS, thereby repressing caspase-3-dependent apoptotic/pyroptotic cell death in the kidneys of AKI mice. Altogether, these results offer a viable approach for synthesizing antioxidant metal phenolic networks mimics to ameliorate ROS-related diseases. • Curcumin-copper-based antioxidant MPNs were prepared. •Cur-Cu@PEG exhibited favorable biocompatibility and kidney-targeted capability. •Cur-Cu@PEG mitigated acute kidney injury by scavenging ROS in vivo . •Cur-Cu@PEG repressed ROS/caspase-3-triggered apoptotic/pyroptotic PCD in AKI kidneys.