A potent and selective anti-glutathione peroxidase 4 nanobody as a ferroptosis inducer.

ABSTRACT: Glutathione peroxidase 4 (GPX4) plays a crucial role in the ferroptosis pathway, emerging as a potential drug target in the treatment of refractory tumors. Unfortunately, the development of GPX4-targeted treatment has been very limited due to the poor selectivity and drug-like properties of current GPX4 inhibitors. Here, we report a proof-of-concept study of potent anti-GPX4 nanobodies, successfully identified through immunizing Bactrian camels and constructing a phage library. Utilizing a cell-penetrating peptide fusion strategy, these nanobodies with high affinities to GPX4 efficiently internalized in cells and formed the basis for further applications. In particular, 12E significantly inhibited cellular GPX4 and consequently induced remarkable ferroptosis in cancer cells. Furthermore, 1

SUBMITTER: Li X 

PROVIDER: S-EPMC11575642 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature