Immune cell-derived membrane nanovesicles: A promethean fire for autoimmune disease therapy through immune cell mimicry.

Abstract

Autoimmune diseases (AIDs) constitute a heterogeneous group of disorders characterized by immune dysregulation, loss of self-tolerance, and chronic inflammation, which leads to tissue damage and organ dysfunction. Current therapies for AIDs are often limited by their lack of specificity, systemic side effects, and insufficient restoration of immune tolerance. Recent advances in nanotechnology and bioengineering have introduced immune and associated cell-derived membrane vesicles (IACMVs) as a promising therapeutic platform. Derived from macrophages, dendritic cells, neutrophils, platelets, or red blood cells, IACMVs inherit key surface proteins and receptors from their parent cells, conferring endogenous biocompatibility, inflammation-specific targeting, and intrinsic immunomodulatory capabilities. These vesicles can be engineered to carry therapeutic cargoes (e.g., peptide inhibitors, nucleic acids) or modified with surface ligands to enhance disease-site specificity, making them versatile tools for specific immunomodulation. This review provides a comprehensive overview of IACMVs, focusing on their preparation techniques, functional mechanisms, and therapeutic applications in prototypical AIDs such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), inflammatory bowel disease (IBD), autoimmune hemolytic anemia (AIHA), type 1 diabetes (T1D), multiple sclerosis (MS), and autoimmune myocarditis (AM). We highlight translational challenges, including production scalability, membrane integrity, immunogenicity, and cargo-loading efficiency, that must be addressed to advance clinical translation. Finally, we discuss future directions for optimizing IACMVs as next-generation, safe, and targeted immunotherapeutic platforms for AIDs.