Chondrocyte membrane-camouflaged selenium nanoplatform with dual targeting for mitochondrial restoration and osteoarthritis therapy.

Precise mitochondrial targeting in chondrocytes is essential for interrupting the vicious cycle of oxidative stress and cartilage degeneration in osteoarthritis (OA). Here, we develop a biomimetic nanoplatform (CM@SS31-Se) with dual targeting capability. This system comprises selenium nanoparticles with glutathione peroxidase mimetic activity as the antioxidant core, SS31 peptide for mitochondrial homing, and chondrocyte membrane coating for homotypic recognition. Following intra-articular injection, the nanoplatform demonstrates prolonged joint retention up to 14 days with favorable biocompatibility. Functionally, the outer membrane shell facilitates chondrocyte internalization through homotypic recognition, the SS31 peptide promotes mitochondrial accumulation through its cardiolipin binding affinity, and the selenium core subsequently provides sustained mtROS scavenging. These dual-targeting properties restore mitochondrial membrane potential and ATP synthesis, upregulate anabolic markers (SOX9, Col II, Aggrecan), and downregulate MMP13 and pro-inflammatory mediators, ultimately promoting the restoration of a regenerative phenotype in degenerative chondrocytes. Thus, this biomimetic nanoplatform enables guided mitochondrial functional restoration, demonstrating therapeutic potential for attenuating OA progression.