A mitochondria-targeted salvianic acid a delivery system for anti-inflammatory treatment of rheumatoid arthritis.

As a bioactive phenolic compound derived from Salvia miltiorrhiza, salvianic acid A (SA) possesses good antioxidant and anti-inflammatory properties to modulate macrophage polarization for Rheumatoid Arthritis (RA) therapy. However, the clinical application of SA is hindered by its low bioavailability and rapid metabolic clearance. Here, we developed a dual-targeted nanoplatform (SAHM-FA/TPP) to specifically target macrophage mitochondria and alleviate RA symptoms. SAHM-FA/TPP encapsulates SA within metal-phenolic networks (MPNs)-coated silica nanoparticles, which was surface-functionalized with Folic Acid (FA) for folate receptor-mediated M-like macrophage Targeting and Triphenylphosphine (TPP) for mitochondrial localization. In vitro studies confirmed its dual-targeting capability, mitochondrial reactive oxygen species (mtROS) scavenging ability and M1-to-M2 repolarization promoting property. In vivo experiments in Collagen-Induced Arthritis (CIA) mice demonstrated its prolonged retention in arthritic joints, significant symptom relief effect and good biosafety. By integrating the antioxidant capabilities of SA with the precise mitochondria-targeting capacity of MPNs, SAHM-FA/TPP offers a promising therapeutic strategy for inflammatory remission in RA.