Engineering nanoplatforms for autoimmune treatment: From synthetic strategies to bioinspired designs

Autoimmune diseases encompass a diverse group of disorders with distinct clinical manifestations but a unifying defect, the breakdown of immune self-tolerance that drives dysregulated immune activation. Current therapies broadly suppress immunity rather than reestablishing regulatory balance and therefore provide limited and often transient control. Building on recent advances in nanomedicine, we introduce an immunoengineering framework that restores immune balance by delivering antigens, co-signals, and tissue repair cues with spatial and temporal precision. This review systematically examines synthetic (liposomes, polymeric nanoparticles, 2D materials), biologically derived and bioinspired (extracellular vesicles, bacterial/viral and cell-membrane vesicles), and hybrid systems, outlining design rules including size and shape, surface chemistry and ligand valency, cargo architecture, and stimuli responsiveness, that govern biodistribution, cellular uptake, and immune programming. Mechanistic principles are illustrated across distinct contexts (e.g., alloantigen responses, mucosal barrier failure, β-cell autoimmunity), emphasizing strategies that induce antigen-specific tolerance, reprogram innate compartments, and repair barriers while preserving protective immunity. We also map key translational needs: standardized characterization and potency assays, long-term safety and biodistribution, scalable manufacturing, regulatory fit, and cost-effectiveness. Together, these insights provide a blueprint for precision nanomedicine to move autoimmunity treatment from blanket suppression toward durable, mechanism-based remission.