Thermal immersion death is an immunogenic programmed cell death, and it is a powerful way to activate anti-cancer immunity. However, it is very challenging to selectively protect normal cells while inducing cancer cells to undergo ferroptosis. In this series, nanoparticles containing Er3+ were screened out. By selectively inducing thermal death of cancer cells, the pancreatic cancer immunotherapy effect was enhanced. To induce tumor-specific inflammatory cell death, a tumor-targeting nanoplatform named Er-RSL3 Inflammation Vesicle Activation System (ERIS) was designed, drawing inspiration from the "Greek discordant goddess", releasing the disharmony within the tumor. ERIS has been proven to induce ferroptosis through lysosomal rupture, which is facilitated by the strong interaction between Er3+ and the lysosomal phospholipid membrane, manifested as a 3.2-fold increase in GSDMD-N cleavage and a 12.2-fold increase in lactate dehydrogenase (LDH) release, all of which are compared to the control group. This local inflammatory attack inhibits tumor growth and promotes anti-cancer immune responses. Therefore, ERIS shows significant tumor suppression effects in different pancreatic cancer models, with minimal systemic side effects, which is achieved through the immune activation induced by thermal immersion and the remodeling of the immunosuppressive tumor microenvironment. This study classifies Er3+ nanoparticles as a novel type of cell-selective intracellular tuning nanotuner, providing a unique opportunity to enhance the efficacy of cancer immunotherapy. This study was published in Advanced Materials under the title "Selective Induction of Cancer Cell Pyroptosis by Erbium Nanotuner Enhances Potent Anti-Cancer Immunity."
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DOI: 10.1002/adma.202522094