February 27, 2019
Ferroptosis is a form of regulated cell death that can be induced by inhibition of the cystine-glutamate antiporter, system xc–. Among the existing system xc– inhibitors, imidazole ketone erastin (IKE) is a potent, metabolically stable inhibitor of system xc– and inducer of ferroptosis potentially suitable for in vivo applications. We investigated the pharmacokinetic and pharmacodynamic features of IKE in a diffuse large B cell lymphoma (DLBCL) xenograft model and demonstrated that IKE exerted an antitumor effect by inhibiting system xc–, leading to glutathione depletion, lipid peroxidation, and the induction of ferroptosis biomarkers both in vitro and in vivo. Using untargeted lipidomics and qPCR, we identified distinct features of lipid metabolism in IKE-induced ferroptosis. In addition, biodegradable polyethylene glycol-poly(lactic-co-glycolic acid) nanoparticles were employed to aid in IKE delivery and exhibited reduced toxicity compared with free IKE in a DLBCL xenograft model.
Publication - Abstract
Feb 26, 2020
International Journal of Molecular Sciences
Publication - Abstract
Jun 03, 2019
Journal of Controlled Release
The lymphatics are a target for a range of therapeutic purposes, including cancer therapy and vaccination and both vesicle size and charge have been considered as factors controlling lymphatic targeting. Within this work, a range...