抗氧化剂
线粒体
重编程
肌萎缩
化学
骨骼肌
线粒体ROS
癌症研究
氧化应激
药理学
氧化磷酸化
医学
生物相容性
细胞生物学
活性氧
生物信息学
粒体自噬
合成代谢
生物
生物化学
自噬
心肌细胞
再生(生物学)
线粒体毒性
杜氏肌营养不良
KEAP1型
线粒体基质
心肌保护
信号转导
作者
Zhang Liu,Zile Shen,Hengli Lu,Bingqiang Lu,Peng Zhang,W J Chen,Guowei Huang,Xinyu Qu,Z. Yu,Feng Chen,Wangfu Zang
出处
期刊:ACS Nano
[American Chemical Society]
日期:2025-12-30
卷期号:20 (1): 1431-1447
标识
DOI:10.1021/acsnano.5c18226
摘要
Sarcopenia, a progressive skeletal muscle disorder marked by loss of mass and function, presents growing societal challenges due to limited therapeutic options. Here, we identify mitochondrial dysfunction and oxidative stress as central drivers of sarcopenia through integrated bioinformatics and clinical validation. To address this pathophysiology, we engineer a muscle-targeted nanocomposite (BP-PEG-MOTS-c, BM) combining mitochondrial-derived peptide MOTS-c with antioxidant black phosphorus nanosheets (BP). BM exhibits dual functionality: MOTS-c restores mitochondrial function, while BP synergistically amplifies ROS scavenging capacity. In cellular and murine models with age-related sarcopenia, BM treatment alleviates muscle dysfunction and muscle loss, concurrently normalizing mitochondrial function and reducing lipid peroxidation. Mechanistic profiling via RNA-seq reveals BM's activation of PI3K/AKT/Nrf2 and suppression of ROS/p38 MAPK signaling pathway, mediating antioxidant responses and maintenance of mitochondrial homeostasis. The nanocomposite demonstrats superior biocompatibility in toxicity assays, outperforming conventional delivery systems. Our findings establish that BM has been established as a promising mitochondrial redox modulator with translational potential for sarcopenia and related age-associated pathologies.
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