Metabolic reprogramming of fibroblast-like synoviocytes with a supramolecular nano-drug for osteoarthritis therapy

Abstract Metabolic reprogramming is fundamental to synovium remodeling with drug delivery for osteoarthritis (OA) therapy. Mitochonic acid 5-MASM7@MnTBAP nanoparticles (MM@MT NPs) with various physicochemical properties and biological activities may be developed as a supramolecular nano-drug delivering to articulus for regulating mitochondrial metabolism of synovium. This study aims to explore the feasibility, efficacy, and mechanism of MM@MT NPs, which possibly excavates a novel perspective for OA therapy. Herein, for feasibility, MM@MT NPs has been indicated to possess excellent photothermal, reactive oxygen species (ROS) response, and oxygen release performances. For efficacy, MM@MT NPs has been confirmed to promote extracellular matrix (ECM) regeneration. For mechanism, MM@MT NPs has been illustrated to restore the mitochondrial membrane potential and recover the mitochondrial dynamics, which is beneficial for maintaining mitochondrial homeostasis. Moreover, MM@MT NPs has been demonstrated to stimulate the tricarboxylic acid (TCA) cycle and oxidative phosphorylation (OXPHOS) in mitochondria as well as enhance antioxidant capacity and eliminate oxidative stress, which is reflected in regulating the adenosine triphosphate (ATP) and ROS metabolism. Therefore, MM@MT NPs can remodel the homeostasis of mitochondria via reprogramming metabolism in synovium, which achieves the symptomatic and etiological treatments of OA.