Immunomodulatory biomimetic nanoparticles target articular cartilage trauma after systemic administration

Abstract

Post-traumatic osteoarthritis (PTOA) is one of the leading causes of disability in developed countries and accounts for 12% of all osteoarthritis cases in the United States. After trauma, inflammatory cells (macrophages amongst others) are quickly recruited within the inflamed synovium and infiltrate the joint space, initiating dysregulation of cartilage tissue homeostasis. Current therapeutic strategies are ineffective, and PTOA remains an open clinical challenge. Here, the targeting potential of liposome-based nanoparticles (NPs) is evaluated in a PTOA mouse model, during the acute phase of inflammation, in both sexes. NPs are composed of biomimetic phospholipids or functionalized with macrophage membrane proteins. Intravenous administration of NPs in the acute phase of PTOA and advanced in vivo imaging techniques reveal preferential accumulation of NPs within the injured joint for up to 7 days post injury, in comparison to controls. Finally, imaging mass cytometry uncovers an extraordinary immunomodulatory effect of NPs that are capable of decreasing the amount of immune cells infiltrating the joint and conditioning their phenotype. Thus, biomimetic NPs could be a powerful theranostic tool for PTOA as their accumulation in injury sites allows their identification and they have an intrinsic immunomodulatory effect.