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Synthetic vectors for activating the driving axis of ferroptosis
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Synthetic vectors for activating the driving axis of ferroptosis
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Journal Article
Synthetic vectors for activating the driving axis of ferroptosis
2024
Overview
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 (LIP
PCPO
) are synthesized to induce ferroptosis by targeting divalent metal transporter 1 (DMT1). LIP
PCPO
is found to boost lysosomal Fe
2+
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, LIP
PCPO
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 LIP
PCPO
and an FDA-approved drug, artesunate, as well as X rays. The formula of LIP
PCPO
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 LIP
PCPO
as a vector to synergize the therapeutic effects of conventional ferroptosis inducers.
Inducers of ferroptosis hold potential for cancer therapy. Here, the authors identify a peroxide-decorated liposome capable of inducing ferroptosis and enhancing the efficacy of chemotherapeutic agents and radiotherapy.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 13/51
/ 14/1
/ 14/19
/ 14/5
/ 59/5
/ 64/60
/ 82/58
/ Animals
/ Breast Neoplasms - drug therapy
/ Breast Neoplasms - metabolism
/ Breast Neoplasms - pathology
/ Divalent metal transporter-1
/ Efflux
/ Female
/ Humanities and Social Sciences
/ Humans
/ Lecithin
/ Mice
/ Phosphatidylcholines - chemistry
/ Phosphatidylcholines - metabolism
/ Phospholipid Hydroperoxide Glutathione Peroxidase - genetics
/ Phospholipid Hydroperoxide Glutathione Peroxidase - metabolism
/ Science
/ Survival
