Spleen-Targeting Delivery of the Liposomal Antigen via an RBC-Based Platform for Cancer Immunotherapy

Efficient delivery of tumor antigens to the spleen remains a challenge for systemic cancer vaccination. Although nanoparticles provide versatile platforms for antigen delivery, intravenous administration often results in preferential sequestration by the reticuloendothelial system, leading to dominant hepatic accumulation and limited spleen-targeting. Here, leveraging the intrinsic splenic clearance property of senescent red blood cells (RBCs), we developed an RBC-based liposomal antigen delivery system by covalently conjugating antigen- and adjuvant-coloaded liposomes onto the RBC surface, thereby inducing senescence-like changes in the carrier RBCs and endowing the modified RBCs with enhanced splenic sequestration. Following intravenous administration, the RBC-liposome vaccine delivery system achieved highly efficient accumulation in the spleen, where the antigen was effectively internalized by splenic immune cells, leading to T cell activation and induction of robust immune responses. This delivery system demonstrated significant therapeutic efficacy in a melanoma-bearing mouse model with a remarkable tumor inhibition rate of 96.5%. Our study might offer a promising strategy for antigen spleen-targeting delivery in cancer immunotherapy.