TY - JOUR
T1 - GSH/pH-Sensitive Poly(glycerol sebacate dithiodiglycolate) Nanoparticle as a Ferroptotic Inducer through Cooperation with Fe3+
AU - Jiang, Yi Sheng
AU - Huang, Cheng Rung
AU - Chen, Chang Shi
AU - Jan, Jeng Shiung
N1 - Publisher Copyright:
© 2024 American Chemical Society.
PY - 2024/1/26
Y1 - 2024/1/26
N2 - 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.
AB - 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.
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U2 - 10.1021/acsapm.3c01770
DO - 10.1021/acsapm.3c01770
M3 - Article
AN - SCOPUS:85182566138
SN - 2637-6105
VL - 6
SP - 1129
EP - 1140
JO - ACS Applied Polymer Materials
JF - ACS Applied Polymer Materials
IS - 2
ER -