Monocyte membrane-coated drug nanocrystals for enhanced targeted therapy of rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic autoimmune disorder with increasing global prevalence. Despite substantial research efforts, the exact etiology of RA remains elusive, and its pathological environment involved appears complicated. To date first-line RA therapies primarily rely on pharmacological interventions, involving chemical and biologic agents that exert systemic immunosuppressive effects or inhibit single signaling molecule blockage. However, these treatments are often associated with significant adverse effects and suboptimal responsiveness. Therefore, the quest for developing innovative RA therapeutic strategies that ensure both high efficacy and robust safety profiles remains a global challenge. In this study, inspired by the natural inflammatory tropism and favorable biocompatibility of monocyte membranes (mMc), we developed a novel platform of mMc-coated drug nanocrystals (mMc@DNCs) with an exceptional drug loading efficiency of approximately 70 %. This system co-formulated an NLRP3 inflammasome inhibitor (MCC950) alongside a reduced dose of dexamethasone (DEX), aiming to simultaneously address both the symptomatic and underlying inflammatory drivers of RA. The therapeutic potential of mMc@DNCs was evaluated in adjuvant-induced arthritis model rats. Following intravenous administration, mMc@DNCs selectively accumulated in inflamed joints, resulting in marked attenuation of joint swelling, bone erosion, and cartilage damage. Moreover, treatment with mMc@DNCs significantly suppressed the expression of pro-inflammatory cytokines TNF-α and IL-1β in the joint cavity. Importantly, this co-formulation exhibited minimal off-target toxicity, suggesting a favorable systemic safety. Hopefully through the investigation it would lay a solid foundation for the development of advanced targeted drug delivery strategies for RA, offering a promising avenue toward safer and more effective therapeutic interventions.