A Platinum(IV) Prodrug—Perfluoroaryl Macrocyclic Peptide Conjugate Enhances Platinum Uptake in the Brain
Colin M. Fadzen, Justin M. Wolfe, Wen Zhou, Choi‐Fong Cho, Niklas von Spreckelsen, Kathryn T. Hutchinson, Yen‐Chun Lee, E. Antonio Chiocca, Sean Lawler, Ömer Yılmaz, Stephen J. Lippard, Bradley L. Pentelute
Abstract
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.
Topics & Concepts
ConjugateProdrugChemistryCisplatinPlatinumPharmacokineticsPeptideGliomaPharmacologyCombinatorial chemistryStereochemistryChemotherapyCancer researchBiochemistryInternal medicineCatalysisMedicineMathematicsMathematical analysisAdvanced biosensing and bioanalysis techniquesNanocluster Synthesis and ApplicationsNanoparticle-Based Drug Delivery