Health Sciences Institute, China Medical University, Shenyang 110122, Liaoning, China; College of Basic Medical Science, Key Laboratory of Medical Cell Biology, Ministry of Education, Key Laboratory of Liaoning Province, China Medical University, Shenyang 110122, Liaoning, China.
Health Sciences Institute, China Medical University, Shenyang 110122, Liaoning, China; College of Basic Medical Science, Key Laboratory of Medical Cell Biology, Ministry of Education, Key Laboratory of Liaoning Province, China Medical University, Shenyang 110122, Liaoning, China; Department of Urology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, Shanxi, China.
Biomaterials. 2025 Mar;314:122863. doi: 10.1016/j.biomaterials.2024.122863. Epub 2024 Sep 27.
Sarcopenia is a progressive skeletal muscle disorder characterized by the accelerated loss of muscle mass and function, with no promising pharmacotherapies. Understanding the imbalance of myoprotein homeostasis within myotubes, which causes sarcopenia, may facilitate the development of novel treatments for clinical use. In this study, we found a strong correlation between low serum selenium levels and muscle function in elderly patients with sarcopenia. We hypothesized that supplementation with selenium might be beneficial for the management of sarcopenia. To verify this hypothesis, we developed diselenide-bridged mesoporous silica nanoparticles (Se-Se-MSNs) with ROS-responsive degradation and release to supplement selenium. Se-Se-MSNs outperformed free selenocysteine in alleviating sarcopenia in both dexamethasone (Dex)- and denervation-induced mouse models. Subsequently, Se-Se-MSNs were loaded with leucine (Leu@Se-Se-MSNs), another nutritional supplement used in sarcopenia management. Oral administration of Leu@Se-Se-MSNs restored myoprotein homeostasis by enhancing mTOR/S6K signaling and inactivating Akt/FoxO3a/MuRF1 signaling, thus exerting optimal therapeutic effects against sarcopenia and exhibiting a more favorable in vivo safety profile. This study provides a proof of concept for treating sarcopenia by maintaining myoprotein and redox homeostasis simultaneously and offers valuable insights into the development of multifunctional nanoparticle-based supplements for sarcopenia management.
肌肉减少症是一种进行性的骨骼肌疾病，其特征是肌肉质量和功能加速丧失，目前尚无有效的药物治疗方法。了解肌管内肌蛋白稳态失衡导致肌肉减少症的机制，可能有助于开发新的治疗方法用于临床应用。在这项研究中，我们发现血清硒水平低与老年肌肉减少症患者的肌肉功能之间存在很强的相关性。我们假设补充硒可能有益于肌肉减少症的治疗。为了验证这一假设，我们开发了具有 ROS 响应性降解和释放的二硒键合介孔硅纳米粒子（Se-Se-MSNs）来补充硒。与游离硒代半胱氨酸相比，Se-Se-MSNs 在地塞米松（Dex）和去神经诱导的小鼠模型中均能更有效地缓解肌肉减少症。随后，将亮氨酸（Leu@Se-Se-MSNs）负载到 Se-Se-MSNs 中，Leu@Se-Se-MSNs 是另一种用于肌肉减少症管理的营养补充剂。亮氨酸（Leu@Se-Se-MSNs）通过增强 mTOR/S6K 信号通路和抑制 Akt/FoxO3a/MuRF1 信号通路来恢复肌蛋白稳态，从而对肌肉减少症发挥最佳的治疗效果，并表现出更有利的体内安全性特征。这项研究为通过同时维持肌蛋白和氧化还原稳态来治疗肌肉减少症提供了概念验证，并为开发用于肌肉减少症管理的多功能纳米粒子基补充剂提供了有价值的见解。
