Biofunctionalized liposomes to monitor rheumatoid arthritis regression stimulated by Interleukin-23 neutralization

Even after the revolution of rheumatoid arthritis (RA) treatment with biologic agents, this debilitating disease remains a major clinical problem. The outstanding outcomes of the systemic administration of antibodies (Abs) are narrowed by the risk of serious side effects and limited efficacy due to their short half-life. Interleukin-23 (IL-23) is a crucial pro-inflammatory cytokine involved in inflammation that potently enhances the generation of T-helper type-17 (Th17) cells. Hence, in this work, anti-IL-23 Abs are immobilized at the surface of liposomes to increase their therapeutic efficacy, being gold nanoparticles (AuNPs) incorporated to allow monitoring the biodistribution of the liposomes after systemic administration as well as due to their anti-inflammatory and antioxidant effects. A stable monodispersed liposomesâ suspension with around 130 nm is produced and efficiently biofunctionalized with anti-IL-23 Abs. IL-23 capture and neutralization capacity are confirmed using activated macrophages. Biological assays demonstrate their hemocompatibility and cytocompatibility with human articular chondrocytes, macrophages, and endothelial cells. Moreover, the neutralization of IL-23 by the biofunctionalized liposomes efficiently decreases the production of IL-17A by peripheral blood mononuclear cells of healthy donors and RA patients who are activated to Th17 differentiation. Therefore, the developed formulation may be a promising strategy to treat RA.The authors acknowledge the financial support from Portuguese Foundation for Science and Technology/Ministry of Science, Technology and Higher Education (FCT/MCTES) and the European Social Fund through the Operational Program of Human Capital (FSE/POCH), for the Ph.D. scholarship PD/BD/11384/2015 of A.C.L. (PD/59/2013), and the FCT for the contracts of A.C. (CEECIND/03628/2017) and C.C. (CEECIND/04601/2017). The authors would also like to acknowledge FCT for the project PTDC/BTM-SAL/28882/2017—Cells4_IDs, and the Northern Portugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (FEDER) (NORTE-01-0145-FEDER-000023-FROnTHERA and NORTE-01-0145-FEDER-000013-PersonalizedNOS), and NORTE 2020 Structured Project within the R&D&I Structured Project, co funded by Norte2020—Programa Operacional Regional do Norte. The authors also acknowledge REMIX Project, funded by the European Union's Horizon 2020 Research and Innovation Programme under the Maria Sklodowska Curie Grant (Agreement No. 778078)