Journal
BIOMATERIALS
Volume 241, Issue -, Pages -Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2020.119911
Keywords
Ferroptosis; Iron redox couple; Ferric ammonium citrate; Liposome; Lipid peroxide
Funding
- National Science and Technology Major Project [2017YFA0205400]
- National Natural Science Foundation of China [81773667, 81573369]
- Project Program of State Key Laboratory of Natural Medicines of China Pharmaceutical University [SKLNMZZJQ201601]
- Outstanding Youth Fund of Jiangsu Province of China [BK20160031]
- 111 Project from the Ministry of Education of China
- State Administration of Foreign Experts Affairs of China [B16046]
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Ferroptosis, a newfound non-apoptotic cell death pathway, results from the accumulation of iron-dependent lipid peroxide (LPO). Recently, emerging iron-based nanomaterials have been extensively developed to induce Fenton reaction-dependent ferroptosis for cancer therapy. However, insufficient amount of H2O2 and limited acidity of tumor could not satisfy the optimal conditions for Fenton reaction, which extremely limited the efficacy of ferroptosis therapy. Herein, we report a novel glutathione (GSH) and iron redox couple sequentially triggered LPO generator (LPOgener) which can directly supply the Fenton reaction-independent downstream executioner of ferroptosis for cancer therapy. By harnessing GSH-mediated Fe3+ reduction and the well-established iron redox couple-mediated lipid peroxidation, LPOgener was constructed by complete ferric ammonium citrate (FAC) and unsaturated lipids-rich phosphatidylcholine, and formed as FAC loaded liposome. The Fe3+ encapsulated in LPOgener could be efficiently reduced to Fe2+ under high GSH level in tumor cells. Subsequently, the formed iron redox couple could trigger overwhelming lipid peroxidation for Fenton reaction-independent ferroptosis. Superior anticancer therapeutic effect with little systemic toxicity demonstrated that LPOgener was a potent ferroptosis-inducing agent for cancer therapy. Therefore, to directly supply the druglike, easily prepared, GSH and iron redox couple sequentially triggered LPOgener would provide a new direction in designing strategies for ferroptosis therapy.
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