2. Academic Validation
  3. Synthetic vectors for activating the driving axis of ferroptosis

Synthetic vectors for activating the driving axis of ferroptosis

  • Nat Commun. 2024 Sep 10;15(1):7923. doi: 10.1038/s41467-024-52312-7.
Jun Jiang # 1 2,  Lili Yang # 1,  Qianqian Xie 1,  Xi Liu 1,  Jie Jiang 1,  Jie Zhang 3,  Shuping Zhang 3,  Huizhen Zheng 1,  Wenjie Li 1,  Xiaoming Cai 4,  Sijin Liu 5 6,  Ruibin Li 7
Affiliations

Affiliations

  • 1 State Key Laboratory of Radiation Medicine and Protection, School for Radiological and Interdisciplinary Sciences (RAD-X), Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Suzhou Medical College, Soochow University, Suzhou, Jiangsu, China.
  • 2 Department of Hepatobiliary and Pancreatic Surgery the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
  • 3 Medical Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, China.
  • 4 School of Public Health, Suzhou Medical College, Soochow University, Suzhou, Jiangsu, China.
  • 5 Medical Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, China. sjliu@rcees.ac.cn.
  • 6 State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, China. sjliu@rcees.ac.cn.
  • 7 State Key Laboratory of Radiation Medicine and Protection, School for Radiological and Interdisciplinary Sciences (RAD-X), Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Suzhou Medical College, Soochow University, Suzhou, Jiangsu, China. liruibin@suda.edu.cn.
  • # Contributed equally.
PMID: 39256387 DOI: 10.1038/s41467-024-52312-7
Abstract

Ferroptosis is a promising strategy for Cancer therapy, with numerous inhibitors of its braking axes under investigation as potential drugs. However, few studies have explored the potential of activating the driving axes to induce Ferroptosis. Herein, phosphatidylcholine peroxide decorating liposomes (LIPPCPO) are synthesized to induce Ferroptosis by targeting divalent metal transporter 1 (DMT1). LIPPCPO is found to boost lysosomal Fe2+ efflux by inducing cysteinylation of lysosomal DMT1, resulting in Glutathione Peroxidase 4 (GPX4) suppression, glutathione depletion and Ferroptosis in breast Cancer cells and xenografts. Importantly, LIPPCPO induced ferroptotic cell death is independent of acquired resistance to radiation, chemotherapy, or targeted agents in 11 Cancer cell lines. Furthermore, a strong synergistic Ferroptosis effect is observed between LIPPCPO and an FDA-approved drug, artesunate, as well as X rays. The formula of LIPPCPO encapsulating artesunate significantly inhibits tumor growth and metastasis and improves the survival rate of breast cancer-bearing female mice. These findings provide a distinct strategy for inducing Ferroptosis and highlight the potential of LIPPCPO as a vector to synergize the therapeutic effects of conventional Ferroptosis inducers.

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