Synovial Fluid Profile Dictates Nanopracticle Uptake into Cartilage- Implications of the Protein Corona for Novel Arthitis Treatments

A major obstacle for joint drug delivery is to penetrate the dense, negatively charged cartilage matrix. Previous studies have extensively investigated particle approaches to cartilage tissue uptake but have neglected to address potential interactions between the particles and the synovial fluid. Here, a NP panel with different PEGylation were incubated with synovial fluid from either rheumatoid or osteoarthritic patients, or FCS. Compared to non-protein covered NPs, we observed a prominent impact of the protein coronas on NP uptake into cartilage, chondrocytes, and monocytes. Utilizing a quantitative proteomics approach, we identified abundant proteins on all panel members irrespective of the NP modifications. Nonetheless, NP and protein condition-specific differences were also observed between the groups. Our study, therefore, suggests that the protein abundance dictates NP efficacy, emphasizing the importance of considering the biological milieu for translating drug delivery designs to the clinic.