A Remote-Controlled Nanopump Delivers Oxygen to Boost Energy Production in Osteoarthritis

release. These processes synergistically enhanced the tricarboxylic acid (TCA) cycle and subsequent oxidative phosphorylation (OXPHOS), thereby promoting adenosine triphosphate (ATP) generation. Mechanistically, in addition to direct oxygen supply, CZIF@Hb nanopump indirectly facilitated the incorporation of α-KG into the TCA cycle by activating the solute carrier family 1 member 5 (SLC1A5)/solute carrier family 38 member 2 (SLC38A2)-glutamate dehydrogenase 1 (GLUD1)-glutaminase (GLS) axis. The enhanced energy metabolism mitigated free radical-induced damage and concurrently promoted the formation of hyaline cartilage instead of fibrocartilage. Administration of CZIF@Hb nanopump exerted therapeutic effects on cartilage degeneration, subchondral bone sclerosis, and synovial inflammation. Overall, the oxygen-carrying nanoplatform offers a feasible strategy for overcoming energy deficits in hypometabolic organs.