2. Academic Validation
  3. Intermetallics triggering pyroptosis and disulfidptosis in cancer cells promote anti-tumor immunity

Intermetallics triggering pyroptosis and disulfidptosis in cancer cells promote anti-tumor immunity

  • Nat Commun. 2024 Oct 8;15(1):8696. doi: 10.1038/s41467-024-53135-2.
Yanlin Zhu 1,  Xinxin Wang 2,  Lili Feng 3,  Ruoxi Zhao 1,  Can Yu 2,  Yuanli Liu 4,  Ying Xie 5,  Bin Liu 1,  Yang Zhou 6,  Piaoping Yang 7
Affiliations

Affiliations

  • 1 Key Laboratory of Superlight Materials and Surface Technology, Ministry of Education, College of Materials Science and Chemical Engineering, Harbin Engineering University, Harbin, PR China.
  • 2 Department of Radiology, Harbin Medical University Cancer Hospital, Harbin, PR China.
  • 3 Key Laboratory of Superlight Materials and Surface Technology, Ministry of Education, College of Materials Science and Chemical Engineering, Harbin Engineering University, Harbin, PR China. fenglili@hrbeu.edu.cn.
  • 4 Department of Biochemistry and Molecular Biology, Harbin Medical University, Harbin, PR China.
  • 5 Key Laboratory of Functional Inorganic Material Chemistry, Ministry of Education, School of Chemistry and Materials Science, Heilongjiang University, Harbin, PR China.
  • 6 Department of Radiology, Harbin Medical University Cancer Hospital, Harbin, PR China. zhouyang094@126.com.
  • 7 Key Laboratory of Superlight Materials and Surface Technology, Ministry of Education, College of Materials Science and Chemical Engineering, Harbin Engineering University, Harbin, PR China. yangpiaoping@hrbeu.edu.cn.
PMID: 39379392 DOI: 10.1038/s41467-024-53135-2
Abstract

Pyroptosis, an immunogenic programmed cell death, could efficiently activate tumor immunogenicity and reprogram immunosuppressive microenvironment for boosting Cancer Immunotherapy. However, the overexpression of SLC7A11 promotes glutathione biosynthesis for maintaining redox balance and countering Pyroptosis. Herein, we develop intermetallics modified with glucose oxidase (GOx) and soybean phospholipid (SP) as Pyroptosis promoters (Pd2Sn@GOx-SP), that not only induce Pyroptosis by cascade biocatalysis for remodeling tumor microenvironment and facilitating tumor cell immunogenicity, but also trigger Disulfidptosis mediated by cystine accumulation to further promote tumor Pyroptosis in female mice. Experiments and density functional theory calculations show that Pd2Sn nanorods with an intermediate size exhibit stronger photothermal and Enzyme catalytic activity compared with the Other three morphologies investigated. The peroxidase-mimic and oxidase-mimic activities of Pd2Sn cause potent Reactive Oxygen Species (ROS) storms for triggering Pyroptosis, which could be self-reinforced by photothermal effect, hydrogen peroxide supply accompanied by glycometabolism, and oxygen production from catalase-mimic activity of Pd2Sn. Moreover, the increase of NADP+/NADPH ratio induced by glucose starvation could pose excessive cystine accumulation and inhibit glutathione synthesis, which could cause Disulfidptosis and further augment ROS-mediated Pyroptosis, respectively. This two-pronged treatment strategy could represent an alternative therapeutic approach to expand anti-tumor immunotherapy.

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