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

  • Nat Commun. 2025 Apr 3;16(1):3194. doi: 10.1038/s41467-025-58354-9.
Zihan Xu  #  1  2  3 ,  Xiujing He  #  1 ,  Yu Gui  #  1 ,  Lingkai Tang  #  4 ,  Yuxin Zhao  5 ,  Linlin Song  1 ,  Tianyue Xu  1 ,  Meixu Chen  1 ,  Yujie Zhao  1 ,  Peixin Du  1 ,  Xin Wang  1 ,  Siyi Chen  6 ,  Yong Luo  2  7 ,  Feng Luo  2  3 ,  Huan Meng  8 ,  Jianping Hu  4 ,  Wei Zhuo  9  10 ,  Jing Jing  11 ,  Hubing Shi  12
Affiliations
  • 1. Institute of Breast Health Medicine, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation Center, Chengdu, Sichuan, China.
  • 2. Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
  • 3. Lung Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
  • 4. Key Laboratory of Medicinal and Edible Plants Resources Development of Sichuan Education Department, School of Pharmacy, Chengdu University, Chengdu, Sichuan, China.
  • 5. Department of Ultrasound, the Affiliated Hospital of Southwest Jiaotong University, the Third People's Hospital of Chengdu City, Chengdu, Sichuan, China.
  • 6. Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
  • 7. Yingshan Hospital, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
  • 8. CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology, Beijing, China.
  • 9. Department of Colorectal Surgery and Oncology, Center for Medical Research and Innovation in Digestive System Tumors, Ministry of Education, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China. [email protected].
  • 10. Department of Cell Biology, Center for Medical Research and Innovation in Digestive System Tumors, Ministry of Education, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China. [email protected].
  • 11. Institute of Breast Health Medicine, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation Center, Chengdu, Sichuan, China. [email protected].
  • 12. Institute of Breast Health Medicine, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation Center, Chengdu, Sichuan, China. [email protected].
  • # Contributed equally.
PMID: 40180981 DOI: 10.1038/s41467-025-58354-9
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.

Products