BSA‐AIE Nanoparticles with Boosted ROS Generation for Immunogenic Cell Death Immunotherapy of Multiple Myeloma

Abstract The main obstacle of multiple myeloma (MM) therapy is the compromised immune microenvironment, which leads to MM relapses and extramedullary disease progression. In this study, a novel strategy is reported of enhanced immunogenic cell death (ICD) immunotherapy with aggregation‐induced emission (AIE) photosensitizer‐loaded bovine serum albumin (BSA) nanoparticles (referred as BSA/TPA‐Erdn), which can activate T cells, convert the cold tumor to hot, and reverse T cell senescence to restore the immune microenvironment for MM treatment. Loading AIE photosensitizer into the hydrophobic domain of BSA proteins significantly immobilizes the molecular geometry, which massively increases reactive oxygen species (ROS) generation and elicits a promising ICD immune response. Employing a NOD‐SCID IL‐2receptor gamma null mice model with MM patients’ monocytes, it is shown that BSA/TPA‐Erdn can simulate human dentric cell maturation, activate functional T lymphocytes, and increase additional polarization and differentiation signals to deliver a promising immunotherapy performance. Intriguingly, for the first time, it is shown that BSA/TPA‐Erdn can greatly reverse T cell senescence, a main challenge in treating MM. Additionally, BSA/TPA‐Erdn can effectively recruit more functional T lymphocytes into MM tumor. As a consequence, BSA/TPA‐Erdn restores MM immune microenvironment and shows the best MM tumor eradication performance, which shall pave new insights for MM treatment in clinical practices.