Dopant‐Regulated Piezocatalysts Evoke Sonopiezoelectric and Enzymatic PANoptosis for Synergistic Cancer Therapy

Abstract Piezocatalyst‐enabled sonopiezoelectric therapy offers noninvasive treatment with high spatiotemporal selectivity, yet existing piezocatalysts are limited by suboptimal efficacy, cancer cell resistance to oxidative stress, and biosafety concerns. Here, hafnia (HfO2), one of the only few FDA...

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Main Authors: Linhong Zhong, Xun Guo, Liming Deng, Xiaoting Wang, Hongye He, Nianhong Wu, Rui Tang, Liang Chen, Yu Chen, Pan Li
Format: Article
Language:English
Published: Wiley 2025-05-01
Series:Advanced Science
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Online Access:https://doi.org/10.1002/advs.202500406
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author Linhong Zhong
Xun Guo
Liming Deng
Xiaoting Wang
Hongye He
Nianhong Wu
Rui Tang
Liang Chen
Yu Chen
Pan Li
author_facet Linhong Zhong
Xun Guo
Liming Deng
Xiaoting Wang
Hongye He
Nianhong Wu
Rui Tang
Liang Chen
Yu Chen
Pan Li
author_sort Linhong Zhong
collection DOAJ
description Abstract Piezocatalyst‐enabled sonopiezoelectric therapy offers noninvasive treatment with high spatiotemporal selectivity, yet existing piezocatalysts are limited by suboptimal efficacy, cancer cell resistance to oxidative stress, and biosafety concerns. Here, hafnia (HfO2), one of the only few FDA‐approved inorganic nanomaterials for clinical trials, is identified as a promising piezocatalyst with high translational potential for sonopiezoelectric and enzymatic PANoptosis‐boosted nanocatalytic therapy. Specifically, engineered transition metal‐substituted HfO2 nanocatalysts are synthesized to optimize piezoelectric and enzyme‐mimicking activities. Among these, Mn‐substituted HfO2 with a 20% Mn ratio (HMO) demonstrates superior performance in sono‐triggered reactive oxygen species generation, attributed to its reduced bandgap and increased oxygen vacancies. HMO also exhibits multiple enzyme‐mimicking activities, including peroxidase (POD), catalase (CAT), and glutathione peroxidase (GPx), amplifying oxidative stress through tumor‐specific catalytic reactions. These dual catalytic effects enable the activation of cancer cell PANoptosis to elicit a robust antitumor immune response. Biological evaluations show significant tumor suppression and antitumor immune responses by HMO‐mediated nanocatalytic therapy. Unlike utilizing the radiosensitization ability of HfO2 in the clinic, this work unveils the distinctive sonopiezoelectric effect and multienzymatic activities of HfO2‐based nanocatalysts for biomedical applications, holding the potential to overcome the challenges of radiation damage associated with radiotherapy.
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spelling doaj-art-c47a48bdb00a4a0cb47b268dd683b61a2025-08-20T02:56:12ZengWileyAdvanced Science2198-38442025-05-011217n/an/a10.1002/advs.202500406Dopant‐Regulated Piezocatalysts Evoke Sonopiezoelectric and Enzymatic PANoptosis for Synergistic Cancer TherapyLinhong Zhong0Xun Guo1Liming Deng2Xiaoting Wang3Hongye He4Nianhong Wu5Rui Tang6Liang Chen7Yu Chen8Pan Li9Ultrasound Department of the Second Affiliated Hospital of Chongqing Medical University Chongqing Key Laboratory of Ultrasound Molecular Imaging Chongqing 400010 P. R. ChinaUltrasound Department of the Second Affiliated Hospital of Chongqing Medical University Chongqing Key Laboratory of Ultrasound Molecular Imaging Chongqing 400010 P. R. ChinaThe First Affiliated Hospital of Chongqing Medical University Chongqing 400010 P. R. ChinaUltrasound Department of the Second Affiliated Hospital of Chongqing Medical University Chongqing Key Laboratory of Ultrasound Molecular Imaging Chongqing 400010 P. R. ChinaUltrasound Department of the Second Affiliated Hospital of Chongqing Medical University Chongqing Key Laboratory of Ultrasound Molecular Imaging Chongqing 400010 P. R. ChinaUltrasound Department of the Second Affiliated Hospital of Chongqing Medical University Chongqing Key Laboratory of Ultrasound Molecular Imaging Chongqing 400010 P. R. ChinaUltrasound Department of the Second Affiliated Hospital of Chongqing Medical University Chongqing Key Laboratory of Ultrasound Molecular Imaging Chongqing 400010 P. R. ChinaMaterdicine Lab School of Life Sciences Shanghai University Shanghai 200444 P. R. ChinaMaterdicine Lab School of Life Sciences Shanghai University Shanghai 200444 P. R. ChinaUltrasound Department of the Second Affiliated Hospital of Chongqing Medical University Chongqing Key Laboratory of Ultrasound Molecular Imaging Chongqing 400010 P. R. ChinaAbstract Piezocatalyst‐enabled sonopiezoelectric therapy offers noninvasive treatment with high spatiotemporal selectivity, yet existing piezocatalysts are limited by suboptimal efficacy, cancer cell resistance to oxidative stress, and biosafety concerns. Here, hafnia (HfO2), one of the only few FDA‐approved inorganic nanomaterials for clinical trials, is identified as a promising piezocatalyst with high translational potential for sonopiezoelectric and enzymatic PANoptosis‐boosted nanocatalytic therapy. Specifically, engineered transition metal‐substituted HfO2 nanocatalysts are synthesized to optimize piezoelectric and enzyme‐mimicking activities. Among these, Mn‐substituted HfO2 with a 20% Mn ratio (HMO) demonstrates superior performance in sono‐triggered reactive oxygen species generation, attributed to its reduced bandgap and increased oxygen vacancies. HMO also exhibits multiple enzyme‐mimicking activities, including peroxidase (POD), catalase (CAT), and glutathione peroxidase (GPx), amplifying oxidative stress through tumor‐specific catalytic reactions. These dual catalytic effects enable the activation of cancer cell PANoptosis to elicit a robust antitumor immune response. Biological evaluations show significant tumor suppression and antitumor immune responses by HMO‐mediated nanocatalytic therapy. Unlike utilizing the radiosensitization ability of HfO2 in the clinic, this work unveils the distinctive sonopiezoelectric effect and multienzymatic activities of HfO2‐based nanocatalysts for biomedical applications, holding the potential to overcome the challenges of radiation damage associated with radiotherapy.https://doi.org/10.1002/advs.202500406enzymatic activityhafnium oxidenanocatalytic therapyPANoptosispiezoelectric biomaterials
spellingShingle Linhong Zhong
Xun Guo
Liming Deng
Xiaoting Wang
Hongye He
Nianhong Wu
Rui Tang
Liang Chen
Yu Chen
Pan Li
Dopant‐Regulated Piezocatalysts Evoke Sonopiezoelectric and Enzymatic PANoptosis for Synergistic Cancer Therapy
Advanced Science
enzymatic activity
hafnium oxide
nanocatalytic therapy
PANoptosis
piezoelectric biomaterials
title Dopant‐Regulated Piezocatalysts Evoke Sonopiezoelectric and Enzymatic PANoptosis for Synergistic Cancer Therapy
title_full Dopant‐Regulated Piezocatalysts Evoke Sonopiezoelectric and Enzymatic PANoptosis for Synergistic Cancer Therapy
title_fullStr Dopant‐Regulated Piezocatalysts Evoke Sonopiezoelectric and Enzymatic PANoptosis for Synergistic Cancer Therapy
title_full_unstemmed Dopant‐Regulated Piezocatalysts Evoke Sonopiezoelectric and Enzymatic PANoptosis for Synergistic Cancer Therapy
title_short Dopant‐Regulated Piezocatalysts Evoke Sonopiezoelectric and Enzymatic PANoptosis for Synergistic Cancer Therapy
title_sort dopant regulated piezocatalysts evoke sonopiezoelectric and enzymatic panoptosis for synergistic cancer therapy
topic enzymatic activity
hafnium oxide
nanocatalytic therapy
PANoptosis
piezoelectric biomaterials
url https://doi.org/10.1002/advs.202500406
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