Radiation-induced ferroptosis via liposomal delivery of 7-Dehydrocholesterol

Radiation-induced ferroptosis via liposomal delivery of 7-Dehydrocholesterol

Abstract Background Ferroptosis is an emerging cell death mechanism characterized by uncontrolled lipid peroxidation. However, selectively inducing ferroptosis in cancer cells remains a challenge. Methods We explore an approach that enables ferroptosis induction through external radiation. The key c...

Full description

Saved in:
Bibliographic Details
Main Authors: Jianwen Li, Shuyue Zhan, Wei Yang, He Zhang, Xinrui Ma, Fanghui Chen, Amy Li, Pakteema Tong, Fangchao Jiang, Zhengwei Cao, Ian Delahunty, Jiayi Wang, Yufei Wu, Zhi Liu, Zibo Li, Yong Teng, Libin Xu, Jin Xie
Format: Article
Language:English
Published: BMC 2025-03-01
Series:Journal of Nanobiotechnology
Subjects:
Liposomes
7-dehydrocholesterol
Radiosensitizer
Lipid peroxidation
Ferroptosis
Online Access:https://doi.org/10.1186/s12951-025-03303-3
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Abstract Background Ferroptosis is an emerging cell death mechanism characterized by uncontrolled lipid peroxidation. However, selectively inducing ferroptosis in cancer cells remains a challenge. Methods We explore an approach that enables ferroptosis induction through external radiation. The key component of this technology is 7-dehydrocholesterol (7DHC), a natural biosynthetic precursor of cholesterol. To facilitate delivery, we demonstrate that 7DHC, like cholesterol, can be incorporated into the lipid layer of liposomes. To enhance targeting, we also introduced NTSmut, a ligand for the neurotensin receptor 1 (NTSR1), which is overexpressed in multiple malignancies, into liposomes. Results Under radiation, 7DHC reacts with radiation-induced reactive oxygen species (ROS), initiating a radical chain reaction with polyunsaturated fatty acids (PUFAs) in cell membranes. This process results in direct lipid peroxidation and subsequent ferroptotic cell death. In vivo studies demonstrate that NTSmut-conjugated, 7DHC-loaded liposomes (N-7DHC-lipos) effectively accumulate in tumors and significantly enhance the efficacy of radiation therapy. Conclusion While conventional radiosensitizers primarily target DNA and its repair mechanisms, our study introduces a strategy to enhance radiotherapy by specifically activating ferroptosis within the irradiated area, thereby minimizing systemic toxicity. Such a strategy of controlled activation of ferroptosis offers a favorable therapeutic index and potentially opens avenues for clinical application.
ISSN:1477-3155

Similar Items