Journal article

Poly(2-oxazoline) – Ferrostatin-1 drug conjugates inhibit ferroptotic cell death

JP Morrow, ZAI Mazrad, AI Bush, K Kempe

Journal of Controlled Release | ELSEVIER | Published : 2022

Abstract

Ferroptosis is a form of non-apoptotic iron induced cell death mechanism implicated in neurodegeneration, yet can be ameliorated with potent radical scavengers such as ferrostatin-1 (Fer-1). Currently, Fer-1 suffers from low water solubility, poor biodistribution profile and is unsuitable for clinical application. Fer-1 polymer-drug conjugates (PDCs) for testing as an anti-ferroptosis therapeutic candidate have yet to be described. Here, we report the synthesis and characterization of a library of water-soluble Fer-1 based poly(2-oxazoline)-drug conjugates. The cationic ring opening polymerization (CROP) of water-soluble 2-oxazoline monomers, and a novel protected aromatic aldehyde 2-oxazoli..

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University of Melbourne Researchers

Grants

Awarded by Australian Research Council


Funding Acknowledgements

We thank Dr. Meike N. Leiske for the discussions about the monomer synthesis. J.P.M. wishes to acknowledge the support received through the Australian Government Research Training Program. Z.A.I.M wishes to acknowledge the Monash Graduate Scholarship. K.K. gratefully ac- knowledges the award of an ARC Future Fellowship (FT190100572) from the Australian Research Council (ARC) . A.I.B. is supported by the Australian National Health and Medical Research Council (GNT1194028) .