A Platinum(IV) Prodrug—Perfluoroaryl Macrocyclic Peptide Conjugate Enhances Platinum Uptake in the Brain

© 2020 American Chemical Society. Effective delivery to the brain limits the development of novel glioblastoma therapies. Here, we introduce conjugation between platinum(IV) prodrugs of cisplatin and perfluoroaryl peptide macrocycles to increase brain uptake. We demonstrate that one such conjugate s...

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Bibliographic Details
Main Authors: Fadzen, Colin M, Wolfe, Justin M, Zhou, Wen, Cho, Choi-Fong, von Spreckelsen, Niklas, Hutchinson, Kathryn T, Lee, Yen-Chun, Chiocca, E Antonio, Lawler, Sean E, Yilmaz, Omer H, Lippard, Stephen J, Pentelute, Bradley L
Other Authors: Massachusetts Institute of Technology. Department of Chemistry
Format: Article
Language:English
Published: American Chemical Society (ACS) 2021
Online Access:https://hdl.handle.net/1721.1/135410
Description
Summary:© 2020 American Chemical Society. Effective delivery to the brain limits the development of novel glioblastoma therapies. Here, we introduce conjugation between platinum(IV) prodrugs of cisplatin and perfluoroaryl peptide macrocycles to increase brain uptake. We demonstrate that one such conjugate shows efficacy against glioma stem-like cells. We investigate the pharmacokinetics of this conjugate in mice and show that the amount of platinum in the brain after treatment with the conjugate is 15-fold greater than with cisplatin after 5 h.