Engineered self-assembly of plant proteins into α-ketoglutarate-loaded nanoplatforms for osteoarthritis treatment.

Osteoarthritis (OA), a chronic degenerative joint disorder characterized by synovial inflammation, cartilage degradation, and osteophyte formation, severely impacts quality of life. Although intra-articular injections achieve high local drug concentrations, rapid synovial diffusion and limited cartilage penetration into the dense cartilage matrix remain major challenges. To address these limitations, we develop a novel self-assembling nanoparticle platform derived from cowpea extracts. By fine-tuning ionic strength and pH, we achieve precise control over the nanoparticle structure, enabling effective drug encapsulation and sustained release. When loaded with α-ketoglutarate (aKG), a small molecular model drug with potential chondroprotective effects, the nanoparticles significantly enhance intra-articular retention and deep cartilage penetration in OA models, leading to marked reductions in synovial inflammation and cartilage degradation. This innovative approach offers a promising targeted strategy for OA treatment and potentially for delivering therapeutics to other dense tissues.