Biomimetic apoptotic erythrocyte membrane-coated microparticles for enhanced tolerance induction

Statement of Purpose: To combat autoimmunity and promote immune tolerance, there is growing interest in therapies that exploit antigen presenting cell (APC)-mediated apoptotic clearance pathways. Tolerized APCs inhibit pathogenic effector T cells and promote formation of protective regulatory T cells.¹ Delivery of self-antigen coupled to apoptotic cells has been shown to induce antigen-specific tolerance to treat autoimmune diseases such as multiple sclerosis without the need for broad immunosuppressants.² However, cell-based therapies are expensive and complex to implement, and alternative “off-the-shelf" strategies are needed. Biocompatible micro-and nanocarriers coated with naturally-derived cell membranes possess key advantages of particle-based delivery platforms while retaining essential cell membrane features to activate apoptotic clearance pathways and promote tolerance. Here we investigate the ability of polymeric microparticles (MPs) with a novel apoptotic red blood cell (RBC)-derived surface coating to enhance APC-mediated tolerance induction. We demonstrate that this apoptotic coating speeds up clearance from systemic circulation, increases APC-mediated uptake, and promotes APC tolerization.