High‐Efficiency Targeted Mitochondrial Transfer and AUTAC4‐Enhanced Dual Renewal Strategy for Rheumatoid Arthritis
Abstract
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.
Article Details
Authors (17)
Fuxiao Wang
Organoid Research Center Institute of Translational Medicine Shanghai University Shanghai P. R. China
Hao Zhang
Dongyang Zhou
Organoid Research Center Institute of Translational Medicine Shanghai University Shanghai P. R. China
Xuan Tang
Key Laboratory for Advanced Materials, Feringa Nobel Prize Scientist Joint Research Center, School of Chemistry and Molecular Engineering
Jian Wang
Han Liu
Department of Chemistry, State Key Laboratory of Synthetic Chemistry, The University of Hong Kong, Pokfulam Road, Hong Kong SAR 999077, P. R. China
Xiuhui Wang
Organoid Research Center Institute of Translational Medicine Shanghai University Shanghai P. R. China
Yuanwei Zhang
Zuhao Li
Department of Orthopedics Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine Shanghai P. R. China
Yingying Jiang
Qin Zhang
State Key Laboratory of Chemo and Biosensing, College of Biology, College of Chemistry and Chemical Engineering
Xiao Chen
Yingying Jing
Organoid Research Center Institute of Translational Medicine Shanghai University Shanghai P. R. China
Ke Xu
Yan Hu
Long Bai
Jiacan Su
Institute of Translational Medicine School of Medicine Shanghai University Shanghai China