Biomimetic\nNanovaccines Restore Immunosuppressive\nTumor Antigen-Presenting Cells via the Saposin-Feeding Strategy

Cancer cell membrane-derived biomimetic\nnanovaccines\nhave shown\ntremendous potential in cancer immunotherapy. However, their efficacy\nis restricted by the insufficient cross-presentation of cell membrane-associated\nantigens. Saposins (SAs), which are vital for membrane vesicle disintegration\nand cell membrane-associated antigen presentation, are severely deficient\nin the antigen-presenting cells (APCs) within tumors. Herein, we propose\na complementary strategy for increasing the efficacy of biomimetic\nnanovaccines via the use of SAs. Biomimetic nanovaccines were designed\nusing cancer cell membrane shells to provide a comprehensive array\nof tumor-associated antigens and reactive oxygen species (ROS)-responsive\nnanoparticle cores that allowed the codelivery of cytosine–guanine\ndinucleotides (CpGs) and SAs. The biomimetic nanovaccines were ROS-responsive\nand highly internalized by APCs, which enabled the release of CpGs\nand SAs in the endo/lysosomes of APCs. Furthermore, biomimetic nanovaccines\nincreased the activation of immunosuppressive APCs and enhanced T-cell\npriming by delivering SAs to the APCs. Consequently, biomimetic nanovaccines\nloaded with SAs not only suppressed tumor growth but also exhibited\nexcellent therapeutic effects in combination with immune checkpoint\nblockade strategies. Overall, our study provides insights into the\ndevelopment of enhanced biomimetic nanovaccines via integrating SAs\nand offers a promising strategy for highly effective cancer immunotherapy.