高效靶向线粒体转移和AUTAC4增强类风湿性关节炎的双重更新策略
High-Efficiency Targeted Mitochondrial Transfer and AUTAC4-Enhanced Dual Renewal Strategy for Rheumatoid Arthritis.
摘要(中文译文)
类风湿性关节炎（RA）是一种慢性自身免疫性疾病，传统生物材料的治疗效果有限，往往缺乏靶向准确性、递送效率和生物相容性。在此，我们提出了一种仿生工程化载体材料，利用线粒体作为“活材料”来恢复RA中的细胞稳态。该双功能载体由叶酸修饰的巨噬细胞膜组成，靶向RA关节中活化的M1巨噬细胞，能够实现原位线粒体转移，递送效率提高两倍以上，这正是当前方法的关键瓶颈。通过促进健康线粒体的精准胞内转移，并结合自噬靶向嵌合体4（AUTAC4）选择性破坏功能障碍的线粒体，该设计实现了线粒体的完全更新，提升了能量代谢和稳态。在RA模型中，双效线粒体更新疗法（DAMRT）显示出显著的治疗潜力。它可作为治疗RA及其他线粒体功能障碍的新型平台。
Abstract
Rheumatoid arthritis (RA) is a chronic autoimmune disease with limited therapeutic effectiveness of conventional biomaterials, which often lack targeted accuracy, delivery efficiency, and biocompatibility. Here, we present a biomimetically engineered carrier material using mitochondria as "living materials" to restore cell homeostasis in RA. The dual action carrier consists of a folic acid-modified macrophage membrane targeting activated M1 macrophages in RA joints, and it enables in situ mitochondrial transfer with more than twofold increase of delivery efficiency, which is a critical limitation of current approaches. By facilitating precise intracellular transfer of healthy mitochondria, and incorporating autophagy targeting chimera 4 (AUTAC4) in order to selectively destroy dysfunctional mitochondria, this design achieves complete mitochondrial renewal, increasing energy metabolism and homeostasis. In an RA model, the Dual-Action Mitochondrial Renewal Therapy (DAMRT) showed significant therapeutic potential. It could be used as a novel platform for treatment for RA and other mitochondrial dysfunction.
如何引用
AMA
Fuxiao Wang, Hao Zhang, Dongyang Zhou, Xuan Tang, Jian Wang, Han Liu, et al. High-Efficiency Targeted Mitochondrial Transfer and AUTAC4-Enhanced Dual Renewal Strategy for Rheumatoid Arthritis.. Advanced materials (Deerfield Beach, Fla.). 2026; doi:10.1002/adma.202514070.
APA
Fuxiao Wang, Hao Zhang, Dongyang Zhou, Xuan Tang, Jian Wang, Han Liu, et al (2026). High-Efficiency Targeted Mitochondrial Transfer and AUTAC4-Enhanced Dual Renewal Strategy for Rheumatoid Arthritis.. Advanced materials (Deerfield Beach, Fla.). https://doi.org/10.1002/adma.202514070
GB/T 7714
Fuxiao Wang, Hao Zhang, Dongyang Zhou, Xuan Tang, Jian Wang, Han Liu, et al. High-Efficiency Targeted Mitochondrial Transfer and AUTAC4-Enhanced Dual Renewal Strategy for Rheumatoid Arthritis.[J]. Advanced materials (Deerfield Beach, Fla.), 2026 doi:10.1002/adma.202514070.
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