Tianyi Wu, Yun Teng, Dawei Song, Yuqi Yang, Huaishuang Shen, Xiao Sun, Rui Chen, Leyu Zhao, Xianggu Zhong, Qi Yan, Junjie Niu, Jun Ge, Liang Cheng, Jun Zou
{"title":"A strategy targeting ferroptosis for mitochondrial reprogramming and intervertebral disc degeneration therapy.","authors":"Tianyi Wu, Yun Teng, Dawei Song, Yuqi Yang, Huaishuang Shen, Xiao Sun, Rui Chen, Leyu Zhao, Xianggu Zhong, Qi Yan, Junjie Niu, Jun Ge, Liang Cheng, Jun Zou","doi":"10.7150/thno.117725","DOIUrl":null,"url":null,"abstract":"<p><p><b>Background:</b> Intervertebral disc degeneration (IVDD) is a leading cause of low back pain, yet current therapies fail to reverse the degenerative process or restore disc function. Ferroptosis, a form of iron-dependent cell death characterized by lipid peroxidation, has been implicated in IVDD progression. <b>Methods:</b> We synthesized Deferoxamine mesylate (DFOM)-loaded cerium oxide nanoparticles (DFOM@CeO<sub>2</sub>) as a novel ferroptosis-targeting therapeutic. <b>Results:</b> DFOM@CeO<sub>2</sub> exhibited dual functionality by scavenging reactive oxygen species (ROS) and chelating excess iron, thereby protecting nucleus pulposus (NP) cells from ferroptosis and extracellular matrix (ECM) degradation. DFOM@CeO<sub>2</sub> demonstrated strong antioxidant capacity, effectively reducing iron accumulation and lipid peroxidation, and restoring glutathione peroxidase 4 (GPX4) expression in NP cells. Furthermore, DFOM@CeO<sub>2</sub> improved mitochondrial respiratory chain function, reduce mitochondrial ROS production and prevent mitochondrial dysfunction. In a rat model of IVDD, DFOM@CeO<sub>2</sub> significantly preserved disc height, reduced ECM degradation, and demonstrated superior therapeutic efficacy compared with DFOM or CeO<sub>2</sub> alone. Transcriptome analysis revealed that DFOM@CeO<sub>2</sub> modulates key ferroptosis-related genes and promotes mitochondrial reprogramming. <b>Conclusions:</b> These findings highlight DFOM@CeO<sub>2</sub> as a promising therapeutic strategy for IVDD, targeting both ferroptosis and mitochondrial dysfunction.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"15 17","pages":"9159-9178"},"PeriodicalIF":13.3000,"publicationDate":"2025-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12439470/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Theranostics","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.7150/thno.117725","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
Background: Intervertebral disc degeneration (IVDD) is a leading cause of low back pain, yet current therapies fail to reverse the degenerative process or restore disc function. Ferroptosis, a form of iron-dependent cell death characterized by lipid peroxidation, has been implicated in IVDD progression. Methods: We synthesized Deferoxamine mesylate (DFOM)-loaded cerium oxide nanoparticles (DFOM@CeO2) as a novel ferroptosis-targeting therapeutic. Results: DFOM@CeO2 exhibited dual functionality by scavenging reactive oxygen species (ROS) and chelating excess iron, thereby protecting nucleus pulposus (NP) cells from ferroptosis and extracellular matrix (ECM) degradation. DFOM@CeO2 demonstrated strong antioxidant capacity, effectively reducing iron accumulation and lipid peroxidation, and restoring glutathione peroxidase 4 (GPX4) expression in NP cells. Furthermore, DFOM@CeO2 improved mitochondrial respiratory chain function, reduce mitochondrial ROS production and prevent mitochondrial dysfunction. In a rat model of IVDD, DFOM@CeO2 significantly preserved disc height, reduced ECM degradation, and demonstrated superior therapeutic efficacy compared with DFOM or CeO2 alone. Transcriptome analysis revealed that DFOM@CeO2 modulates key ferroptosis-related genes and promotes mitochondrial reprogramming. Conclusions: These findings highlight DFOM@CeO2 as a promising therapeutic strategy for IVDD, targeting both ferroptosis and mitochondrial dysfunction.
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.