Ultrasound-responsive nanoparticles for releasing intact HMGB1 in cancer immunotherapy
발표자
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초록
내용
HMGB1 protein is a crucial damage-associated molecular pattern, able to stimulate antigen presenting cells, thus priming the T cells towards a cytotoxic response. During cancer therapy, HMGB1 readily undergoes inactivation by caspase-3. Hence exploiting HMGB1 associated cancer immune therapy is not easy to achieve. Here we report a self-assembling nanoparticle (NP) composed of PFP gas precursor. The acoustic cavitation effect of NPs upon ultrasound exposure triggers inflation of PFP, facilitating cell-membrane rupture resulting release of intact HMGB1. Accordingly, the extracellular HMGB1 provoke an antitumor immune response by the maturation of dendritic cells and activating cytotoxic T cells. Additionally, combination therapy of NPs with immune checkpoint inhibitor ensured abolition of the primary tumor in CT26 tumor-bearing mouse model. In summary, we established a novel NP based approach to enhance cancer immunotherapy by eliciting caspase independent immunogenic cancer cell death.