Ultrasound initiated tumor catalytic PANoptosis by mesoporous piezoelectric nanocatalysts

Abstract Background PANoptosis has been identified as a robust inflammatory cell death pathway triggered upon host defense against invaded pathogens such as bacteria and viruses, however, pathogen-free tumor PANoptosis has not been achieved yet. Reactive oxygen and nitrogen species capable of induci...

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Main Authors: Xuan-Shou Xu, Wei-Wei Ren, Heng Zhang, Dong-Liang Huo, Qi Lyu, Mei-Xiao Zhan, Hui-Xiong Xu, Li-Ying Wang, Min-Feng Huo, Jian-Lin Shi
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Language:English
Published: BMC 2025-07-01
Series:Military Medical Research
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Online Access:https://doi.org/10.1186/s40779-025-00629-9
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author Xuan-Shou Xu
Wei-Wei Ren
Heng Zhang
Dong-Liang Huo
Qi Lyu
Mei-Xiao Zhan
Hui-Xiong Xu
Li-Ying Wang
Min-Feng Huo
Jian-Lin Shi
author_facet Xuan-Shou Xu
Wei-Wei Ren
Heng Zhang
Dong-Liang Huo
Qi Lyu
Mei-Xiao Zhan
Hui-Xiong Xu
Li-Ying Wang
Min-Feng Huo
Jian-Lin Shi
author_sort Xuan-Shou Xu
collection DOAJ
description Abstract Background PANoptosis has been identified as a robust inflammatory cell death pathway triggered upon host defense against invaded pathogens such as bacteria and viruses, however, pathogen-free tumor PANoptosis has not been achieved yet. Reactive oxygen and nitrogen species capable of inducing robust and diverse cell death pathways such as pyroptosis, apoptosis, and necroptosis are supposed to be the potential triggers for tumor PANoptosis by ultrasound (US)-controlled sono-piezodynamic therapy. Methods S-nitrosothiols (SNO)-zinc peroxide (ZnO2)@cyclic dinucleotide (CDN)@mesoporous tetragonal barium titanate (mtBTO) nanoparticles (NZCB NPs) were synthesized by hydrothermal method with subsequent annealing, in situ growth, and finally surface functionalization. Scanning electron microscopy, transmission electron microscopy, X-ray diffraction, atomic force microscopy, Fourier transform infrared spectroscopy, and electron spin resonance were used for materials characterizations. Murine melanoma B16 cells are employed to investigate the in vitro US-initiated tumor PANoptosis by NZCB NPs. In vivo US-initiated tumor PANoptosis was investigated on B16 tumor-bearing C57BL/6J mice. Results A “boiling-bubbling” strategy is developed to endow the piezoelectric BTO nanocatalysts, with mesoporous architecture, which enables the encapsulation of the immune-agonist CDN (9.4 wt%) to initiate innate immunity of the host. Then, SNO-functionalized ZnO2 was further employed to cap the mesoporous nanocatalysts, forming multifunctional piezocatalytic NZCB NPs. Under US irradiation, intracellular massive reactive oxygen and nitrogen species such as superoxide anion radicals, nitric oxide (NO), and peroxynitrite (ONOO−) could be produced from the piezoelectric NZCB NPs, which, synergized with CDN-triggered antitumoral immunity, lead to highly immunogenic tumor PANoptosis by NZCB NPs through the tumor microenvironment remodeling. Intratumoral injection of NZCB NPs leads to substantial tumor PANoptosis with immune potentiation, ultimately destroying the tumor xenografts effectively. Conclusion The present work presents the mesostructure design of piezocatalytic nanomaterials and the crosstalk between oxidative stress and antitumor immunity within the tumor, facilitating promising tumor PANoptosis by nanocatalytic oxidation with high effectiveness and biocompatibility.
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spelling doaj-art-40f5350b4839498cb689a0d5b3394b6f2025-08-20T03:42:23ZengBMCMilitary Medical Research2054-93692025-07-0112112110.1186/s40779-025-00629-9Ultrasound initiated tumor catalytic PANoptosis by mesoporous piezoelectric nanocatalystsXuan-Shou Xu0Wei-Wei Ren1Heng Zhang2Dong-Liang Huo3Qi Lyu4Mei-Xiao Zhan5Hui-Xiong Xu6Li-Ying Wang7Min-Feng Huo8Jian-Lin Shi9Department of Medical Ultrasound, Shanghai Tenth People’s Hospital, Shanghai Frontiers Science Center of Nanocatalytic Medicine, the Institute for Biomedical Engineering and Nano Science School of Medicine, Tongji University School of MedicineDepartment of Medical Ultrasound, Shanghai Tenth People’s Hospital, Shanghai Frontiers Science Center of Nanocatalytic Medicine, the Institute for Biomedical Engineering and Nano Science School of Medicine, Tongji University School of MedicineDepartment of Ultrasound, Zhuhai People’s Hospital (the Affiliated Hospital of Beijing Institute of Technology, Zhuhai Clinical Medical College of Jinan University)Department of Medical Ultrasound, Shanghai Tenth People’s Hospital, Shanghai Frontiers Science Center of Nanocatalytic Medicine, the Institute for Biomedical Engineering and Nano Science School of Medicine, Tongji University School of MedicineDepartment of Ultrasound, Zhongshan Hospital, Institute of Ultrasound in Medicine and Engineering, Fudan UniversityDepartment of Ultrasound, Zhuhai People’s Hospital (the Affiliated Hospital of Beijing Institute of Technology, Zhuhai Clinical Medical College of Jinan University)Department of Ultrasound, Zhongshan Hospital, Institute of Ultrasound in Medicine and Engineering, Fudan UniversityDepartment of Medical Ultrasound, Shanghai Tenth People’s Hospital, Shanghai Frontiers Science Center of Nanocatalytic Medicine, the Institute for Biomedical Engineering and Nano Science School of Medicine, Tongji University School of MedicineDepartment of Medical Ultrasound, Shanghai Tenth People’s Hospital, Shanghai Frontiers Science Center of Nanocatalytic Medicine, the Institute for Biomedical Engineering and Nano Science School of Medicine, Tongji University School of MedicineDepartment of Medical Ultrasound, Shanghai Tenth People’s Hospital, Shanghai Frontiers Science Center of Nanocatalytic Medicine, the Institute for Biomedical Engineering and Nano Science School of Medicine, Tongji University School of MedicineAbstract Background PANoptosis has been identified as a robust inflammatory cell death pathway triggered upon host defense against invaded pathogens such as bacteria and viruses, however, pathogen-free tumor PANoptosis has not been achieved yet. Reactive oxygen and nitrogen species capable of inducing robust and diverse cell death pathways such as pyroptosis, apoptosis, and necroptosis are supposed to be the potential triggers for tumor PANoptosis by ultrasound (US)-controlled sono-piezodynamic therapy. Methods S-nitrosothiols (SNO)-zinc peroxide (ZnO2)@cyclic dinucleotide (CDN)@mesoporous tetragonal barium titanate (mtBTO) nanoparticles (NZCB NPs) were synthesized by hydrothermal method with subsequent annealing, in situ growth, and finally surface functionalization. Scanning electron microscopy, transmission electron microscopy, X-ray diffraction, atomic force microscopy, Fourier transform infrared spectroscopy, and electron spin resonance were used for materials characterizations. Murine melanoma B16 cells are employed to investigate the in vitro US-initiated tumor PANoptosis by NZCB NPs. In vivo US-initiated tumor PANoptosis was investigated on B16 tumor-bearing C57BL/6J mice. Results A “boiling-bubbling” strategy is developed to endow the piezoelectric BTO nanocatalysts, with mesoporous architecture, which enables the encapsulation of the immune-agonist CDN (9.4 wt%) to initiate innate immunity of the host. Then, SNO-functionalized ZnO2 was further employed to cap the mesoporous nanocatalysts, forming multifunctional piezocatalytic NZCB NPs. Under US irradiation, intracellular massive reactive oxygen and nitrogen species such as superoxide anion radicals, nitric oxide (NO), and peroxynitrite (ONOO−) could be produced from the piezoelectric NZCB NPs, which, synergized with CDN-triggered antitumoral immunity, lead to highly immunogenic tumor PANoptosis by NZCB NPs through the tumor microenvironment remodeling. Intratumoral injection of NZCB NPs leads to substantial tumor PANoptosis with immune potentiation, ultimately destroying the tumor xenografts effectively. Conclusion The present work presents the mesostructure design of piezocatalytic nanomaterials and the crosstalk between oxidative stress and antitumor immunity within the tumor, facilitating promising tumor PANoptosis by nanocatalytic oxidation with high effectiveness and biocompatibility.https://doi.org/10.1186/s40779-025-00629-9Piezoelectric nanocatalystTumor PANoptosisSonodynamic therapyImmunotherapyMesopore engineering
spellingShingle Xuan-Shou Xu
Wei-Wei Ren
Heng Zhang
Dong-Liang Huo
Qi Lyu
Mei-Xiao Zhan
Hui-Xiong Xu
Li-Ying Wang
Min-Feng Huo
Jian-Lin Shi
Ultrasound initiated tumor catalytic PANoptosis by mesoporous piezoelectric nanocatalysts
Military Medical Research
Piezoelectric nanocatalyst
Tumor PANoptosis
Sonodynamic therapy
Immunotherapy
Mesopore engineering
title Ultrasound initiated tumor catalytic PANoptosis by mesoporous piezoelectric nanocatalysts
title_full Ultrasound initiated tumor catalytic PANoptosis by mesoporous piezoelectric nanocatalysts
title_fullStr Ultrasound initiated tumor catalytic PANoptosis by mesoporous piezoelectric nanocatalysts
title_full_unstemmed Ultrasound initiated tumor catalytic PANoptosis by mesoporous piezoelectric nanocatalysts
title_short Ultrasound initiated tumor catalytic PANoptosis by mesoporous piezoelectric nanocatalysts
title_sort ultrasound initiated tumor catalytic panoptosis by mesoporous piezoelectric nanocatalysts
topic Piezoelectric nanocatalyst
Tumor PANoptosis
Sonodynamic therapy
Immunotherapy
Mesopore engineering
url https://doi.org/10.1186/s40779-025-00629-9
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