Nanomedicine Strategies for Autoimmune Diseases: Targeting and Reprogramming Macrophages

ABSTRACT In recent years, the incidence and complexity of autoimmune diseases (AIDs) have been steadily increasing, posing grim challenges to clinical management. These diseases often involve multi‐organ dysfunction and impose a pronounced burden on patients' physical and mental health. Current therapeutic strategies remain suboptimal, frequently limited by poor specificity and severe systemic side effects. With the rapid advancement of nanotechnology, nanodrugs have emerged as a potential approach on account of their enhanced targeting capability, high therapeutic efficacy, and reduced toxicity. In particular, macrophage‐targeted nanodrugs have gained considerable attention, given that macrophages act as a key mediator in the onset and progression of various AIDs. This review systematically summarizes the molecular basis of macrophage involvement in autoimmunity, the design strategies of nanodrugs, and their applications across different AIDs, including rheumatoid arthritis (RA), inflammatory bowel disease (IBD), multiple sclerosis (MS), psoriasis (PSO), and systemic lupus erythematosus (SLE). These nanodrugs exert their therapeutic effects primarily by modulating macrophage‐mediated immune responses, specifically through reprogramming macrophage phenotypes to promote anti‐inflammatory and tissue‐reparative functions. By precisely reprogramming macrophage function, these nanotherapeutics offer a novel approach for AID treatment.