Anran Zhang, Haiyang Gao, Xianglong Chen, Pengzhi Shi, Zhangrong Cheng, Yuhang Chen, Wang Wu, Wenbo Wu, Cao Yang, Yukun Zhang
{"title":"Tailorable bimetallic nanozyme mitigates intervertebral disc degeneration by inhibiting oxidative stress and inflammageing.","authors":"Anran Zhang, Haiyang Gao, Xianglong Chen, Pengzhi Shi, Zhangrong Cheng, Yuhang Chen, Wang Wu, Wenbo Wu, Cao Yang, Yukun Zhang","doi":"10.7150/thno.108592","DOIUrl":null,"url":null,"abstract":"<p><p><b>Rationale:</b> Scavenging reactive oxygen species (ROS), modulating extracellular matrix (ECM) anabolism, and preventing senescence of nucleus pulposus cells (NPCs) are crucial factors of treatment approaches for intervertebral disc degeneration (IDD). However, addressing these issues simultaneously has been challenging due to the interactions among the various pathological factors in the disc microenvironment. <b>Methods:</b> Herein, we utilize self-assembly technology and the excellent drug-carrying potential of mesoporous Prussian blue to design a tailorable bimetallic nanozyme platform of a Mn-modified mesoporous Prussian blue loaded with Cibotium barometz (MPB-Mn3-CB) for the treatment of IDD. <b>Results:</b> The enhancement of multiple antioxidant enzyme activities by MPB-Mn3-CB is ascribed to the lower activation energy of the MnN<sub>4</sub> active site compared to the FeN<sub>4</sub> active site. <i>In vitro</i> and <i>in vivo</i> experiments show that MPB-Mn3-CB efficiently scavenges ROS, promotes ECM synthesis, and rescues the senescent phenotype of NPCs by inhibiting the P53 pathway. <b>Conclusion:</b> This work addresses the specific microenvironmental challenges in severe IDD by synchronously tackling multiple interacting pathological factors and provides a potential therapeutic strategy by multifunctional bimetallic nanozyme for IDD treatment.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"15 14","pages":"6957-6982"},"PeriodicalIF":12.4000,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12203817/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Theranostics","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.7150/thno.108592","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"Q1","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
引用次数: 0
Abstract
Rationale: Scavenging reactive oxygen species (ROS), modulating extracellular matrix (ECM) anabolism, and preventing senescence of nucleus pulposus cells (NPCs) are crucial factors of treatment approaches for intervertebral disc degeneration (IDD). However, addressing these issues simultaneously has been challenging due to the interactions among the various pathological factors in the disc microenvironment. Methods: Herein, we utilize self-assembly technology and the excellent drug-carrying potential of mesoporous Prussian blue to design a tailorable bimetallic nanozyme platform of a Mn-modified mesoporous Prussian blue loaded with Cibotium barometz (MPB-Mn3-CB) for the treatment of IDD. Results: The enhancement of multiple antioxidant enzyme activities by MPB-Mn3-CB is ascribed to the lower activation energy of the MnN4 active site compared to the FeN4 active site. In vitro and in vivo experiments show that MPB-Mn3-CB efficiently scavenges ROS, promotes ECM synthesis, and rescues the senescent phenotype of NPCs by inhibiting the P53 pathway. Conclusion: This work addresses the specific microenvironmental challenges in severe IDD by synchronously tackling multiple interacting pathological factors and provides a potential therapeutic strategy by multifunctional bimetallic nanozyme for IDD treatment.
期刊介绍:
Theranostics serves as a pivotal platform for the exchange of clinical and scientific insights within the diagnostic and therapeutic molecular and nanomedicine community, along with allied professions engaged in integrating molecular imaging and therapy. As a multidisciplinary journal, Theranostics showcases innovative research articles spanning fields such as in vitro diagnostics and prognostics, in vivo molecular imaging, molecular therapeutics, image-guided therapy, biosensor technology, nanobiosensors, bioelectronics, system biology, translational medicine, point-of-care applications, and personalized medicine. Encouraging a broad spectrum of biomedical research with potential theranostic applications, the journal rigorously peer-reviews primary research, alongside publishing reviews, news, and commentary that aim to bridge the gap between the laboratory, clinic, and biotechnology industries.