Modulating inflammation through the neutralization of Interleukin-6 and tumor necrosis factor-α by biofunctionalized nanoparticles

Abstract

Biological agents that neutralize the activity of pro-inflammatory cytokines are revolutionizing the treatment of inflammatory conditions. However, the antibodies (Abs) short half-life and off-target distribution critically limit their efficacy and safety. Therefore, this work proposes the immobilization of anti-TNF-α and anti-IL-6 Abs at the surface of polymeric nanoparticles (NPs) in order to extend and increase the Abs therapeutic efficacy, owing to the protection from degradation that the NPs provide, and to avoid off-target side effects through local administration. In an in vitro model of inflammation, biofunctionalized NPs were able to reduce the harmful effects on human chondrocytes provided by inflammatory macrophages, being demonstrated the additive effects of the dual neutralization. Significantly, biofunctionalized NPs ameliorated inflammation more efficiently than soluble Abs in an in vivo experimental model of inflammation, exhibiting a safe profile, a prolonged action, and a stronger efficacy. Hence, as this strategy is able to increase the therapeutic efficacy of the currently available treatments, it is a promising potential therapeutic option for inflammatory conditions.

Keywords: Antibodies immobilization; Inflammation; Interleukin-6 and tumor necrosis factor-α neutralization; Polymeric nanoparticles.