Inflammasome mediated in situ cancer vaccine activated by schottky heterojunction for augmented immunotherapy

Abstract

In situ cancer vaccines have emerged as an attractive paradigm for cancer immunotherapy. Nevertheless, insufficient antigens production, weak antigen presentation and immunosuppressive tumor microenvironment impeded the effectiveness of tumor immunotherapy. Herein, we constructed the NLRP3 inflammasome mediated in situ cancer vaccine (FPLB), in which rod shaped α-Fe₂O₃@Pt schottky heterojunction loaded with lactate oxidase (LOx) and surface-modified with bovine serum albumin and folic acid conjugation (FA-BSA). On the one hand, FPLB NPs utilizes its physicochemical properties of high aspect ratio to induce the breakdown of dendritic cells (DCs) lysosomes and the release of cathepsin B, thereby activating the NLRP3 inflammasome. Besides, the formation of “circulating pump” by harnessing catalase (CAT) activity and LOx activity could continuously consume lactic acid to alleviate the inactivation of cytokines induced by lactic acid excess, thereby transforming inflammatory activators into controllable nanoadjuvants. On the other hand, the “circulating pump” not only catalyze continuous generation of pyruvic acid to block the cell cycle, but also boosts charge utilization efficiency for excellent sonodynamic therapy (SDT) effect under ultrasound irradiation, thereby inducing the apoptosis or necrosis of tumor cells and releasing tumor-associated antigens (TAAs). FPLB demonstrates a significant NLRP3-mediated anti-tumor immune response both in vitro and in vivo. This strategy provides a new paradigm for the construction of NLRP3 inflammasome-mediated in situ cancer vaccines, which will have profound implications for the application of immunotherapy.