Nanomedicine and Spleen-Targeting Strategies for Precision Immunomodulation: Advances, Challenges, and Future Perspectives

The spleen, which is the largest lymphoid organ, contains various immune cells and plays a crucial role in immunological responses. Because nanoparticles have a natural characteristic of being taken up by reticuloendothelial system (RES) organs, including the spleen, various spleen-targeting nanomedicine strategies have been developed for immunomodulatory therapies. Herein, we review the biological role of the spleen as part of the immune system, types of spleen-targeting nanoparticles, considerations for engineering both current and innovative spleen-targeting strategies, and their therapeutic potential in various diseases, including tumors and autoimmune diseases. Furthermore, we discuss the importance of systems immunology based approaches, including spatial transcriptomics, in achieving a comprehensive understanding of spleen-targeting strategies using nanomedicine.