一种参与能量代谢的纳米药物维持线粒体稳态以减轻细胞衰老。
An energy metabolism-engaged nanomedicine maintains mitochondrial homeostasis to alleviate cellular ageing.
作者信息
Chen Liyuan, Fan Yijie, Jiang Nan, Huang Xiaoshuai, Yu Min, Zhang He, Xu Zhengren, He Danqing, Wang Yu, Ding Chengye, Wu Xiaolan, Li Chang, Zhang Shiying, Liu Hangbo, Shi Xinmeng, Zhang Fanghui, Zhang Ting, Luo Dan, Wang Cunyu, Liu Yan
机构信息
Department of Orthodontics, National Center for Stomatology, National Clinical Research Center for Oral Diseases, National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Beijing Key Laboratory of Digital Stomatology, Research Center of Engineering and Technology for Computerized Dentistry Ministry of Health, NMPA Key Laboratory for Dental Materials, National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Peking University School and Hospital of Stomatology, Beijing, People's Republic of China.
Beijing Institute of Nanoenergy and Nanosystems, Chinese Academy of Sciences, Beijing, People's Republic of China.
出版信息
Nat Nanotechnol. 2025 Aug 19. doi: 10.1038/s41565-025-01972-7.
Energy restriction is closely related to cellular senescence and species longevity. Here, based on the structure and function of ATP synthase, a key enzyme for energy generation, we develop energy metabolism-engaged nanomedicines (EM-eNMs) to rejuvenate aged stromal/stem cells, and help to prevent skeletal ageing. We show that EM-eNMs infiltrate the mitochondria of aged bone marrow mesenchymal stromal/stem cells (BMMSCs), driving mitochondrial fission, mitophagy, glycolysis and maintaining BMMSC stemness and multifunction. The EM-eNMs directly bind to the ATP synthase and promote mitophagy through induction of the dynamin-related protein 1 (DRP1) gene. Remarkably, EM-eNMs selectively target bone tissues through systemic delivery and significantly reverse osteoporotic bone loss in aged mice by enhancing mitochondrial fission and mitophagy, while simultaneously restoring the stemness and osteogenic potential of aged BMMSCs in situ. Taken together, our findings highlight the potential of the EM-eNMs as a targeted therapy to alleviate cellular senescence and age-related diseases.
能量限制与细胞衰老和物种寿命密切相关。在此，基于能量生成的关键酶ATP合酶的结构和功能，我们开发了参与能量代谢的纳米药物（EM-eNMs），以使衰老的基质/干细胞恢复活力，并有助于预防骨骼衰老。我们表明，EM-eNMs渗入衰老的骨髓间充质基质/干细胞（BMMSCs）的线粒体，驱动线粒体分裂、线粒体自噬、糖酵解，并维持BMMSC的干性和多功能性。EM-eNMs直接与ATP合酶结合，并通过诱导动力相关蛋白1（DRP1）基因促进线粒体自噬。值得注意的是，EM-eNMs通过全身给药选择性地靶向骨组织，并通过增强线粒体分裂和线粒体自噬显著逆转老年小鼠的骨质疏松性骨质流失，同时原位恢复衰老BMMSC的干性和成骨潜力。综上所述，我们的研究结果突出了EM-eNMs作为一种靶向疗法减轻细胞衰老和与年龄相关疾病的潜力。
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