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Parallel Lipid Peroxide Accumulation Strategy Based on Bimetal–Organic Frameworks for Enhanced Ferrotherapy
Author(s) -
Xin Hao,
Wang Fang,
Luo Rengan,
Lei Jianping
Publication year - 2021
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.202005114
Subject(s) - peroxide , lipid peroxide , chemistry , glutathione , porphyrin , radical , inducer , gpx4 , biochemistry , lipid peroxidation , glutathione peroxidase , oxidative stress , organic chemistry , enzyme , gene
Ferroptosis, a nonapoptotic cell‐death pathway, is commonly regulated by ether lipid peroxide generation or glutathione consumption. In this work, a parallel lipid peroxide accumulation strategy was designed based on catalytic metal–organic frameworks (MOFs) for enhanced ferrotherapy. The bimetallic MOF was synthesized with iron porphyrin as a linker and cupric ion as a metal node, and erastin, a ferroptosis inducer, was sandwiched between the MOF layers with 4,4′‐dipyridyl disulfide as spacers. In a tumor microenvironment, erastin was released from the layered MOFs through glutathione‐responsive cleavage. The exfoliated MOFs served as a dual Fenton reaction inducer to generate numerous hydroxyl radicals for the accumulation of lipid peroxide, while erastin‐aggravated glutathione depletion down‐regulated glutathione peroxidase 4; this then inhibited the consumption of lipid peroxide. Therefore, a parallel lipid peroxide accumulation strategy was established for enhanced ferrotherapy that effectively inhibited tumor growth in live mice, opening up new opportunities to treat apoptosis‐insensitive tumors.