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 - Summary
Nov 15, 2016
International Journal of Pharmaceutics
Liposomes are lipid-based supramolecular assemblies that can be engineered into efficacious drug carriers. Typically described as bilayer systems with an aqueous core, liposomes can increase the therapeutic index of a given drug molecule by decreas...
Publication - Summary
Jan 19, 2016
Proceedings of the National Academy of Sciences
Liver cancer is a deadly disease with limited intervention options. Tumour removal surgery and liver transplantation are extremely complicated and not always possible. Several small molecule drugs aimed to treat hepatocellular carcinoma (HCC) have ...