posted on 2024-01-10, 12:03authored byYi-Sheng Jiang, Cheng-Rung Huang, Chang-Shi Chen, Jeng-Shiung Jan
Ferroptosis
is an iron-dependent, non-apoptotic cell death induced
by an overload of iron initiated through Fenton and Haber–Weiss
reactions. These two reactions lead to lethal levels of intracellular
reactive oxygen species (ROS) and lipid peroxidation. In contrast,
glutathione (GSH) and glutathione peroxidase 4 (GPX4) suppress ferroptosis
by inhibiting lipid peroxidation. Herein, the ferric ion (Fe3+) carriers, poly(glycerol sebacate dithiodiglycolate) nanoparticles
(PGSDTG NPs), were prepared via nanoprecipitation. The GSH/pH-dual
sensitive Fe3+/PGSDTG NPs would disintegrate via the cleavage
of disulfide and ester bonds in the presence of GSH and acidic conditions.
The cleaved polymer segments along with released Fe3+ rendered
cancer cells showing ferroptosis characteristics including ROS production,
transferrin receptor 1 (TfR1) expression, and iron accumulation after
treatment with Fe3+/PGSDTG NPs. The PGSDTG NPs played an
important role in ferroptosis by triggering the oxidation of intracellular
GSH and reducing the GPX4 expression. An in vivo experiment
also showed that Caenorhabditis elegans (C. elegans) exhibited a shortened
lifespan after treatment with NPs. These results indicated that the
PGSDTG NPs were potential GSH/pH-sensitive metal ion carriers for
anticancer treatment by inducing ferroptosis.