Lithospermic acid etched ZIF-8 nanoparticles delays osteoarthritis progression by inhibiting inflammatory signaling pathways and rescuing mitochondrial damage

Osteoarthritis (OA) is the most common chronic inflammatory joint disease. Improving the joint inflammatory microenvironment is expected to promote early intervention and delay the progression of OA. However, effective strategies for inhibiting OA-related joint inflammation are still lacking. Lithospermic acid (LA), a polycyclic phenol carboxylic acid extracted from salvia miltiorrhiza, has strong anti-inflammatory and antioxidant effects. However, its role in the treatment of OA and the underlying mechanisms are unclear. To improve the bioavailability of LA, an LA synergistic protects etched zeolitic imidazolate framework (ZIF)-8 nanoparticles (LA@ZIF-8) was designed and developed for targeted delivery to modulate the inflammatory microenvironment in OA. This study confirmed that LA@ZIF-8 inhibits the pro-inflammatory phenotype of RAW264.7 macrophages through the NF-ĸB signaling pathway, effectively alleviates mitochondrial dysfunction, and delays articular cartilage degeneration caused by the joint inflammatory microenvironment mediated by synoval macrophages. In summary, LA@ZIF-8 delays the progression of OA by inhibiting synovial macrophage-mediated inflammatory responses, highlighting its clinical application potential.