High-Efficiency Targeted Mitochondrial Transfer and AUTAC4-Enhanced Dual Renewal Strategy for Rheumatoid Arthritis

  • Adv Mater. 2026 Jun;38(32):e14070. doi: 10.1002/adma.202514070.
Fuxiao Wang  1  2 ,  Hao Zhang  3 ,  Dongyang Zhou  1  2 ,  Xuan Tang  1  2 ,  Jian Wang  4 ,  Han Liu  1  2 ,  Xiuhui Wang  1  2 ,  Yuanwei Zhang  3 ,  Zuhao Li  3 ,  Yingying Jiang  1  2 ,  Qin Zhang  1  2 ,  Xiao Chen  3 ,  Yingying Jing  1  2 ,  Ke Xu  1  2  5  6 ,  Yan Hu  3 ,  Long Bai  1  2  5 ,  Jiacan Su  1  2  3
Affiliations
  • 1. Organoid Research Center, Institute of Translational Medicine, Shanghai University, Shanghai, P. R. China.
  • 2. National Center for Translational Medicine (Shanghai) SHU Branch, Shanghai University, Shanghai, P. R. China.
  • 3. Department of Orthopedics, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, P. R. China.
  • 4. Department of Diagnostic Radiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
  • 5. Wenzhou Institute of Shanghai University, Zhejiang, P. R. China.
  • 6. Sanming Institute of Translational Medicine, Sanming, P. R. China.
PMID: 41691414 DOI: 10.1002/adma.202514070
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.

Keywords
AUTAC4; living material; macrophage reprogramming; mitochondrial transfer; rheumatoid arthritis.
Products