Erythrocyte membrane-camouflaged and double-factor sequential delivery nanocarriers postpone the progression of osteoarthritis

Osteoarthritis is a commonly severe joint disease featured by the progressive loss of cartilage and reduction in lubricating synovial fluid, which currently lacks the effective treatment in clinic. Herein, we designed an erythrocyte membrane-camouflaged and double-factor sequential delivery of shell-core nanocarrier to deliver two diverse drugs. The interior core of nanocarriers was loaded with the transforming growth factor-β3 (TGF-β3), and subsequently modified with a natural anti-inflammatory drug of curcumin, and finally encapsulated with erythrocyte membrane as a protective and regulation shell. The as-prepared engineered nanocarriers were injected into joint capsule to play a dual function on inflammation modulation and cartilage remodeling. The curcumin absorbed on the internal surface of shell membrane was firstly released in large quantities to tune the inflammatory microenvironment whereas the TGF-β3 in the interior core was released subsequently with the nanoparticle degradation to alleviate chondrocyte senescence. Overall, our current work creates an engineered nanocarrier to control macrophage type and induce cartilage restoration on postponing the progression of osteoarthritis.