Dismantlable Coronated Nanoparticles for Coupling the Induction and Perception of Immunogenic Cell Death

Therapy-induced immunogenic cell death (ICD) can initiate both innate and adaptive immune responses for amplified anti-tumor efficacy. However, dying cell-released ICD signals are prone to being sequestered by the TIM-3 receptors on dendritic cell (DC) surfaces, preventing immune surveillance. Herein, dismantlable coronated nanoparticles (NPs) are fabricated as a type of spatiotemporally controlled nanocarriers for coupling tumor cell-mediated ICD induction to DC-mediated immune sensing. These NPs are loaded with an ICD inducer, mitoxantrone (MTO), and wrapped by a redox-labile anti-TIM-3 (alpha TIM-3) antibody corona, forming a separable core-shell structure. The antibody corona disintegrates under high levels of extracellular reactive oxygen species in the tumor microenvironment, exposing the MTO-loaded NP core for ICD induction and releasing functional alpha TIM-3 molecules for DC sensitization. Systemic administration of the coronated NPs augments DC maturation, promotes cytotoxic T cell recruitment, enhances tumor susceptibility to immune checkpoint blockade, and prevents the side effects of MTO. This study develops a promising nanoplatform to unleash the potential of host immunity in cancer therapy. Dismantlable coronated nanoparticles are fabricated as spatiotemporally controlled nanocarriers for coupling immunogenic cell death (ICD) induction to immune perception. The covalently cross-linked antibody corona shell disassembles in the tumor microenvironment, enables dual ICD modulations within tumor cells and on dendritic cell surfaces, promotes cytotoxic T cell recruitment, and sensitizes tumors to immune checkpoint blockade in breast and colorectal cancers. image