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, we report a novel strategy of enhanced immunogenic cell death (ICD) immunotherapy with aggregation-induced emission (AIE) photosensitizer-loaded BSA nanoparticles (referred as BSA/TPA-Erdn), which could 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 elicit a promising ICD immune response. Employing a NOD-SCID IL-2receptor gamma null mice model with MM patients’ monocytes, we show that BSA/TPA-Erdn could simulate human DC maturation, activate functional T lymphocytes, and increase additional polarization and differentiation signals to deliver a promising immunotherapy performance. Intriguingly, we show for the first time that BSA/TPA-Erdn could greatly reverse T cell senescence, a main challenge in treating MM. Additionally, BSA/TPA-Erdn could effectively recruit more functional T lymphocytes into MM tumor. As a consequence, BSA/TPA-Erdn restored MM immune microenvironment and shows the best MM tumor eradication performance, which shall pave new insights for MM treatment in clinical practices.

Advanced Materials. ( IF 32.086 ) DOI: 10.1002/adma.202208692