Antioxidant Cerium Oxide Nanoparticle Coatings Impart Immunomodulatory Effects by Suppressing Antigen-Specific Cytotoxic T Cell Activation

Abstract

Cellular entrapment within biostable hydrogels can decrease immunological rejection by blocking direct contact between the host and transplanted cells; however, these implants remain susceptible to deleterious inflammatory and immunological responses that can dampen their therapeutic effect. Reactive oxygen species (ROS) are key agents that facilitate these responses. While ROS is commonly attributed to general inflammation and cytotoxicity, it also plays an important role in the activation of adaptive immune cells, as ROS-mediated pathways facilitate the efficient generation of effector T cells. Herein, we explored if incorporating a potent antioxidant, specifically cerium oxide nanoparticles (CONP), onto the surface of a hydrogel-based microbead platform could deliver an immunomodulatory biomaterial capable of dampening antigen-specific effector T cell generation. To test this hypothesis, CONP-based coatings were applied to the surface of cell-containing alginate microbeads and co-cultured with immune cells. Quantification of the immune responses found that CONP-coatings decreased the generation of antigen-specific effector CD8⁺ T cells. Interrogation of T cell and antigen-presenting cell (APC) responses found suppression was likely driven by the modulation of CD8⁺ T cells, as APCs were only modestly impacted. Results provide insight into the capacity of CONP to deliver an immunomodulatory effect. These findings also highlight the general potential of antioxidant biomaterials to serve a dual role in protecting cells from ROS-mediated damage and suppressing adaptive immune cell responses.