Antigen-specific nanomedicines for the treatment of autoimmune disease: target cell types, mechanisms and outcomes.

Nanoparticle (NP)-based delivery of autoantigenic ligands represents a promising approach to modulate autoimmune responses in vivo. Over the last 15 years, a growing number of compounds have been tested in animal models of various experimental and/or spontaneous autoimmune diseases. Based on the underlying design principles and mechanistic underpinnings, these compounds can be categorized into three broad groups: NPs (or microparticles, MPs) as vehicles for targeted delivery of antigens to tolerogenic antigen-presenting cells (APCs); NPs as scaffolds for targeted delivery of both antigen and immunomodulatory molecules to professional APCs; and NPs as multimerization platforms for direct cognate T-cell targeting via recombinant peptide-major histocompatibility complex molecules (pMHCs). These various compounds operate through different mechanisms of action, eliciting pharmacodynamic effects that range from antigen-specific clonal deletion to induction of comprehensive, yet disease-specific, bystander immunoregulation. Here, we review the outcomes of the various approaches tested to date and discuss their translational significance in the context of mode of action vis-à-vis immunologically complex human autoimmune diseases.