Abstract
AbstractMessenger RNA (mRNA)‐based therapies have emerged as a revolutionary strategy for treating various diseases. In autoimmune diseases like rheumatoid arthritis (RA), targeted mRNA delivery provides a potential intervention to modulate immune responses. However, achieving specific and efficient in vivo modulation of immune regulators, such as the inhibitory Fc gamma receptor, FcγRIIB, on B cells remains challenging. In this study, lipid polymer nanoparticles (LPNs) formulated with AMB‐POC18 lipidoid and poly(ethylene glycol)‐block‐polylactide (PEG‐PLA) are engineered to deliver FcγRIIB mRNA (mFcγRIIB) specifically to splenic B cells for RA treatment. Protein corona analysis indicated that selective adsorption of complement C3 on the LPNs' surface facilitated their targeted delivery to the spleen, enhancing transfection efficiency in B cells following intravenous administration. In a collagen‐induced arthritis mouse model, mFcγRIIB/LPNs effectively upregulated FcγRIIB expression in splenic B cells, significantly reducing autoimmune responses and alleviating RA symptoms. Further mechanistic studies elucidated that increased FcγRIIB expression suppressed B cell activation via the FcγRIIB/Lyn/SHP‐1 signaling pathway. This work underscored the potential of the spleen‐targeted mRNA delivery system for RA therapy, providing a precise and targeted approach to modulate B cell activity and mitigate autoimmune diseases.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
