A strategy targeting ferroptosis for mitochondrial reprogramming and intervertebral disc degeneration therapy.

IF 13.3 1区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL
Theranostics Pub Date : 2025-08-16 eCollection Date: 2025-01-01 DOI:10.7150/thno.117725
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
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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.

针对铁下垂的线粒体重编程和椎间盘退变治疗策略。
背景:椎间盘退变(IVDD)是腰痛的主要原因,但目前的治疗方法无法逆转退变过程或恢复椎间盘功能。铁死亡是一种以脂质过氧化为特征的铁依赖性细胞死亡形式,与IVDD的进展有关。方法:我们合成了甲磺酸去铁胺(DFOM)负载的氧化铈纳米颗粒(DFOM@CeO2)作为一种新型的针对铁中毒的治疗药物。结果:DFOM@CeO2具有清除活性氧(ROS)和螯合过量铁的双重功能,从而保护髓核(NP)细胞免受铁凋亡和细胞外基质(ECM)降解。DFOM@CeO2显示出强大的抗氧化能力,有效地减少铁积累和脂质过氧化,恢复NP细胞中谷胱甘肽过氧化物酶4 (GPX4)的表达。此外,DFOM@CeO2改善线粒体呼吸链功能,减少线粒体ROS的产生,防止线粒体功能障碍。在IVDD大鼠模型中,DFOM@CeO2显著保留了椎间盘高度,减少了ECM降解,与单独使用DFOM或CeO2相比,显示出更好的治疗效果。转录组分析显示DFOM@CeO2调节铁凋亡相关的关键基因并促进线粒体重编程。结论:这些发现强调DFOM@CeO2是IVDD的一种有希望的治疗策略,针对铁下垂和线粒体功能障碍。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Theranostics
Theranostics MEDICINE, RESEARCH & EXPERIMENTAL-
CiteScore
25.40
自引率
1.60%
发文量
433
审稿时长
1 months
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.
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