In vivo assembly enhanced binding effect augments tumor specific ferroptosis therapy

Da-Yong Hou, Dong-Bing Cheng, Ni-Yuan Zhang, Zhi-Jia Wang, Xing-Jie Hu, Xin Li, Mei-Yu Lv, Xiang-Peng Li, Ling-Rui Jian, Jin-Peng Ma, Taolei Sun (), Zeng-Ying Qiao (), Wanhai Xu () and Hao Wang ()
Additional contact information
Da-Yong Hou: National Center for Nanoscience and Technology (NCNST)
Dong-Bing Cheng: Wuhan University of Technology
Ni-Yuan Zhang: National Center for Nanoscience and Technology (NCNST)
Zhi-Jia Wang: National Center for Nanoscience and Technology (NCNST)
Xing-Jie Hu: National Center for Nanoscience and Technology (NCNST)
Xin Li: Wuhan University of Technology
Mei-Yu Lv: Harbin Medical University
Xiang-Peng Li: National Center for Nanoscience and Technology (NCNST)
Ling-Rui Jian: Harbin Medical University
Jin-Peng Ma: Harbin Medical University
Taolei Sun: Wuhan University of Technology
Zeng-Ying Qiao: National Center for Nanoscience and Technology (NCNST)
Wanhai Xu: Harbin Medical University
Hao Wang: National Center for Nanoscience and Technology (NCNST)

Nature Communications, 2024, vol. 15, issue 1, 1-16

Abstract: Abstract Emerging evidence indicates that the activation of ferroptosis by glutathione peroxidase 4 (GPX4) inhibitors may be a prominent therapeutic strategy for tumor suppression. However, the wide application of GPX4 inhibitors in tumor therapy is hampered due to poor tumor delivery efficacy and the nonspecific activation of ferroptosis. Taking advantage of in vivo self-assembly, we develop a peptide-ferriporphyrin conjugate with tumor microenvironment specific activation to improve tumor penetration, endocytosis and GPX4 inhibition, ultimately enhancing its anticancer activity via ferroptosis. Briefly, a GPX4 inhibitory peptide is conjugated with an assembled peptide linker decorated with a pH-sensitive moiety and ferriporphyrin to produce the peptide-ferriporphyrin conjugate (Gi-F-CAA). Under the acidic microenvironment of the tumor, the Gi-F-CAA self-assembles into large nanoparticles (Gi-F) due to enhanced hydrophobic interaction after hydrolysis of CAA, improving tumor endocytosis efficiency. Importantly, Gi-F exhibits substantial inhibition of GPX4 activity by assembly enhanced binding (AEB) effect, augmenting the oxidative stress of ferriporphyrin-based Fenton reaction, ultimately enabling antitumor properties in multiple tumor models. Our findings suggest that this peptide-ferriporphyrin conjugate design with AEB effect can improve the therapeutic effect via induction of ferroptosis, providing an alternative strategy for overcoming chemoresistance.

Date: 2024
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-023-44665-2 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-023-44665-2

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-023-44665-2

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().