A novel mRNA nanovaccine with dual immunoregulation ameliorates rheumatoid arthritis and associated pneumonia.

Rheumatoid arthritis (RA) as a systemic autoimmune disease, frequently triggers various extra-articular symptoms, particularly the RA-associated pneumonia. Unfortunately, the RA-associated pneumonia has garnered insufficient attention, and conventional RA therapies may exacerbate pneumonia-related complications, thereby complicating the treatment process. Herein, a novel dual immunoregulatory mRNA nanovaccine (MPDA@RC@HM) is designed for the efficient treatment of RA and RA-associated pneumonia simultaneously. This innovative mRNA nanovaccine represents a highly organized nanostructure that integrates the rapamycin-loaded mesoporous polydopamine (MPDA) with mRNA encoding the epitope of type Ⅱ collagen, and the surface is modified with hyaluronic acid and dendritic cell membrane. After intravenous injection into collagen-induced arthritis mice, the mRNA nanovaccine exhibits effective distribution and transfection within the spleen and lung, subsequently exerting potent immunoregulation in both organs, thereby yielding a dual therapeutic effect. This study presents a versatile mRNA nanovaccine platform for the treatment of autoimmune diseases and provides an innovative approach for addressing RA and RA-associated pneumonia.