Protective effect of platinum nano-antioxidant and nitric oxide against hepatic ischemia-reperfusion injury

Jing Mu, Chunxiao Li, Yu Shi, Guoyong Liu, Jianhua Zou, Dong-Yang Zhang, Chao Jiang, Xiuli Wang, Liangcan He (), Peng Huang (), Yuxin Yin () and Xiaoyuan Chen ()
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Jing Mu: Peking University Shenzhen Hospital
Chunxiao Li: Tongji University
Yu Shi: Peking University Shenzhen Hospital
Guoyong Liu: Peking University Shenzhen Hospital
Jianhua Zou: National University of Singapore
Dong-Yang Zhang: Shenzhen University
Chao Jiang: Shenzhen University
Xiuli Wang: Tongji University
Liangcan He: Harbin Institute of Technology
Peng Huang: Shenzhen University
Yuxin Yin: Peking University Shenzhen Hospital
Xiaoyuan Chen: National University of Singapore

Nature Communications, 2022, vol. 13, issue 1, 1-12

Abstract: Abstract Therapeutic interventions of hepatic ischemia-reperfusion injury to attenuate liver dysfunction or multiple organ failure following liver surgery and transplantation remain limited. Here we present an innovative strategy by integrating a platinum nanoantioxidant and inducible nitric oxide synthase into the zeolitic imidazolate framework-8 based hybrid nanoreactor for effective prevention of ischemia-reperfusion injury. We show that platinum nanoantioxidant can scavenge excessive reactive oxygen species at the injury site and meanwhile generate oxygen for subsequent synthesis of nitric oxide under the catalysis of nitric oxide synthase. We find that such cascade reaction successfully achieves dual protection for the liver through reactive oxygen species clearance and nitric oxide regulation, enabling reduction of oxidative stress, inhibition of macrophage activation and neutrophil recruitment, and ensuring suppression of proinflammatory cytokines. The current work establishes a proof of concept of multifunctional nanotherapeutics against ischemia-reperfusion injury, which may provide a promising intervention solution in clinical use.

Date: 2022
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DOI: 10.1038/s41467-022-29772-w

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