Tools for Antigen Delivery: From Traditional Nanocarriers and Biomimetic Platforms to Emerging Physical, Bioengineered and Computational Approaches.

The magnitude and quality of adaptive immune responses are fundamentally influenced by the efficiency of antigen presentation. Traditional vaccine platforms, such as live-attenuated or inactivated pathogens, although immunogenic, often present safety concerns. Conversely, subunit vaccines, despite being safer, generally exhibit poor immunogenicity due to inadequate delivery of antigens to professional antigen-presenting cells (APCs). To address this issue, the development of innovative delivery systems has become a pivotal strategy to overcome significant biological barriers, including extracellular antigen degradation, suboptimal lymph node targeting, and inefficient cross-presentation necessary for CD8+ T cell activation. This review systematically explores recent advancements in delivery technologies aimed at enhancing antigen presentation, encompassing rationally engineered nanocarriers and sophisticated biomimetic platforms. We first examine how nanoparticle properties like size, surface charge, and ligand density affect intracellular trafficking and the transition from MHC-II to MHC-I cross-presentation. Then, we explore bioinspired systems such as extracellular vesicles, virus-like particles, and cell-membrane-coated nanoparticles that utilize natural biological traits for enhanced targeting and immune modulation. Additionally, we review new physical delivery methods like microneedle arrays and in situ electroporation for direct, minimally invasive antigen delivery to dendritic cells. Lastly, we discuss the potential of these platforms in personalized cancer vaccines and combination immunotherapies. By combining insights from materials science, immunology, and bioengineering, these next-generation delivery tools could enhance antigen presentation and transform precision vaccination and immune intervention.