Biomimetic dual-catalytic nanozyme remodels the liver fibrotic microenvironment to alleviate fibrosis.
4 affiliations
- 1Department of Ultrasound, Affiliated Hospital of Southwest Jiaotong University, The Third People's Hospital of Chengdu, Chengdu 610031, China.
- 2School of Medical Imaging, North Sichuan Medical College, Nanchong 637000, China.
- 3College of Medicine, Southwest Jiaotong University, Chengdu 610031, China.
- 4Department of Ultrasound, Huili People's Hospital, Liangshan 615100, China.
Abstract
Activated hepatic stellate cells (HSCs) are the primary drivers of pathological extracellular matrix accumulation in liver fibrosis. Thus, inhibiting HSC activation is crucial for treatment; however, therapeutic efficacy often falls short of expectations. A major obstacle is the hypoxic, reactive oxygen species (ROS)-rich microenvironment, which fuels persistent HSC activation and compromises long-term treatment success. Here, we developed an activated HSC-targeted biomimetic nanozyme, HSC-HMMDN, by coating hollow mesoporous manganese dioxide nanoparticles (HMMDN) with membranes derived from activated HSCs to synergistically clear ROS and alleviate hypoxia. This homologous coating strategy enables precise recognition of surface adhesion molecules (such as integrins and N-cadherin) that are highly expressed on activated HSCs, ensuring targeted delivery. Once there, the nanozyme, endowed with superoxide dismutase- and catalase-like activities, scavenges excessive ROS, revives mitochondrial function and suppresses the TGF-β/Smad cascade to inhibit HSC activation. In a carbon tetrachloride (CCl4)-induced liver fibrosis rat model, HSC-HMMDN significantly ameliorated fibrosis and alleviated the hypoxic microenvironment without showing detectable toxicity. Overall, this targeted microenvironment remodeling strategy provides a new avenue for liver fibrosis therapy.
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BibTeX
@article{tang2026biomimetic,
title = {{Biomimetic dual-catalytic nanozyme remodels the liver fibrotic microenvironment to alleviate fibrosis.}},
author = {Xueyao Tang and Juying Zhang and Jixuan Zhang and Lei Huang and Changbao Li and Hong Zhou and Ming Ye and Jujie Du and Yang Liu and Yang Zhou and Ying Liu},
journal = {Regenerative biomaterials},
year = {2026},
month = nov,
doi = {10.1093/rb/rbag163},
url = {https://europepmc.org/article/MED/42997765},
note = {CC BY},
}
RIS
TY - JOUR
TI - Biomimetic dual-catalytic nanozyme remodels the liver fibrotic microenvironment to alleviate fibrosis.
AU - Xueyao Tang
AU - Juying Zhang
AU - Jixuan Zhang
AU - Lei Huang
AU - Changbao Li
AU - Hong Zhou
AU - Ming Ye
AU - Jujie Du
AU - Yang Liu
AU - Yang Zhou
AU - Ying Liu
PY - 2026
DA - 2026/11/03
JO - Regenerative biomaterials
DO - 10.1093/rb/rbag163
UR - https://europepmc.org/article/MED/42997765
AB - Activated hepatic stellate cells (HSCs) are the primary drivers of pathological extracellular matrix accumulation in liver fibrosis. Thus, inhibiting HSC activation is crucial for treatment; however, therapeutic efficacy often falls short of expectations. A major obstacle is the hypoxic, reactive oxygen species (ROS)-rich microenvironment, which fuels persistent HSC activation and compromises long-term treatment success. Here, we developed an activated HSC-targeted biomimetic nanozyme, HSC-HMMDN, by coating hollow mesoporous manganese dioxide nanoparticles (HMMDN) with membranes derived from activated HSCs to synergistically clear ROS and alleviate hypoxia. This homologous coating strategy enables precise recognition of surface adhesion molecules (such as integrins and N-cadherin) that are highly expressed on activated HSCs, ensuring targeted delivery. Once there, the nanozyme, endowed with superoxide dismutase- and catalase-like activities, scavenges excessive ROS, revives mitochondrial function and suppresses the TGF-β/Smad cascade to inhibit HSC activation. In a carbon tetrachloride (CCl4)-induced liver fibrosis rat model, HSC-HMMDN significantly ameliorated fibrosis and alleviated the hypoxic microenvironment without showing detectable toxicity. Overall, this targeted microenvironment remodeling strategy provides a new avenue for liver fibrosis therapy.
SN - 2056-3418
SN - 2056-3426
ER -