Intrapleural pressure-controlled piezo-catalytic nanozyme for the inhibition of malignant pleural effusion

Zihan Xu, Xiujing He, Yu Gui, Lingkai Tang, Yuxin Zhao, Linlin Song, Tianyue Xu, Meixu Chen, Yujie Zhao, Peixin Du, Xin Wang, Siyi Chen, Yong Luo, Feng Luo, Huan Meng, Jianping Hu, Wei Zhuo (), Jing Jing () and Hubing Shi ()
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Zihan Xu: Sichuan University and Collaborative Innovation Center
Xiujing He: Sichuan University and Collaborative Innovation Center
Yu Gui: Sichuan University and Collaborative Innovation Center
Lingkai Tang: Chengdu University
Yuxin Zhao: the Third People’s Hospital of Chengdu City
Linlin Song: Sichuan University and Collaborative Innovation Center
Tianyue Xu: Sichuan University and Collaborative Innovation Center
Meixu Chen: Sichuan University and Collaborative Innovation Center
Yujie Zhao: Sichuan University and Collaborative Innovation Center
Peixin Du: Sichuan University and Collaborative Innovation Center
Xin Wang: Sichuan University and Collaborative Innovation Center
Siyi Chen: Sichuan University
Yong Luo: Sichuan University
Feng Luo: Sichuan University
Huan Meng: National Center for Nanoscience and Technology
Jianping Hu: Chengdu University
Wei Zhuo: Zhejiang University School of Medicine
Jing Jing: Sichuan University and Collaborative Innovation Center
Hubing Shi: Sichuan University and Collaborative Innovation Center

Nature Communications, 2025, vol. 16, issue 1, 1-20

Abstract: Abstract Malignant pleural effusion (MPE), persistently generated by thorax tumor cells at the advanced stage, remains a major challenge for cancer therapy. Herein, we develop an ultra-sensitive piezoelectric nano-system by doping ytterbium in metal-organic framework (O3P@LPYU), which can be triggered by physiological intrapleural pressure during breath. Under the gently alterative pressure, the piezoelectric nanoparticles with notable peroxidase-like activity effectively produce a burst of reactive oxygen species and induce immunogenic cell death by catalysis of carried ozone as well as peroxide in interstitial fluid. A clear and sustained biodistribution is observed in thorax effusion and tumors upon intrapleural administration of particle. Remarkably, due to the abundant substrates in oxygen-rich environment of pleural cavity, O3P@LPYU particle provides a potent reduction of MPE volume and durable inhibition of tumor growth in thorax. Our work not only develops a bio-responsive piezoelectric nano-system, but also provides a strategy for persistent suppression of MPE in clinics.

Date: 2025
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DOI: 10.1038/s41467-025-58354-9

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