Induction of Tumor Ferroptosis-Dependent Immunity via an Injectable Attractive Pickering Emulsion Gel.

The combination of ferroptosis inducers and immune checkpoint blockade (ICB) can enhance antitumor effects. However, the efficacy in tumors with low immunogenicity requires further investigation. Herein, we have developed a water-in-oil Pickering emulsion gel to deliver (1S, 3R)-RSL-3 (RSL-3), a ferroptosis inducer dissolved in iodized oil and programmed death-1 (PD-1) antibody, the most commonly used immune checkpoint inhibitor dissolved in water, with optimal characteristics (RSL-3+PD-1@gel). Tumor lipase degrades the continuous oil phase, which results in the slow release of RSL-3 and PD-1 antibody and a notable antitumor effect against low-immunogenic hepatocellular carcinoma (HCC) and pancreatic cancer. Intriguingly, the RSL-3+PD-1@gel induces ferroptosis of tumor cells, resulting in antitumor immune response via accumulation of helper T lymphocyte cells and cytotoxic T cells. Additionally, the single cell sequence profiling analysis during tumor treatment reveals the induction of ferroptosis in tumor cells together with strong antitumor immune response in ascites. This article is protected by copyright. All rights reserved.