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

• Published in: Advanced materials (Weinheim) Vol. 35; no. 35; pp. e2303542 - n/a
• Main Authors: Dai, Xiaomeng, Zhang, Jia, Bao, Xuanwen, Guo, Yixuan, Jin, Yuzhi, Yang, Chenjing, Zhang, Hangyu, Liu, Lulu, Gao, Yang, Ye, Chanqi, Wu, Wei, Liu, Chuan, Zhao, Chun‐Xia, Sheng, Jianpeng, Ren, En, Li, Hongjun, Fang, Weijia, Wu, Baiheng, Ruan, Jian, Gu, Zhen, Chen, Dong, Zhao, Peng
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 01.09.2023
• Subjects: Antibodies; Anticancer properties; Cancer; cancer immunotherapy; drug delivery; ferroptosis; immune checkpoint blockade; Immune system; Lymphocytes; Materials science; ferroptosis; drug delivery; cancer immunotherapy; immune checkpoint blockade
• ISSN: 0935-9648; 1521-4095
• DOI: 10.1002/adma.202303542

The combination of ferroptosis inducers and immune checkpoint blockade can enhance antitumor effects. However, the efficacy in tumors with low immunogenicity requires further investigation. In this work, a water‐in‐oil Pickering emulsion gel is developed 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 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. A water‐in‐oil Pickering emulsion gel is developed to deliver RSL‐3, a ferroptosis inducer dissolved in iodized oil, and programmed death‐1 (PD‐1) antibody, an immune checkpoint inhibitor dissolved in water. RSL‐3 + PD‐1@gel induces ferroptosis of tumor cells through cascade amplification and elicits antitumor immune responses via accumulation of helper T lymphocyte cells and cytotoxic T cells in tumors with low immunogenicity.