Schiff-Base Cross-Linked Poly(2-oxazoline) Micelle Drug Conjugates Possess Antiferroptosis Activity in Numerous In Vitro Cell Models

A great deal of nanocarriers have been applied to induce ferroptosis in cancer research, yet there are limited examples of nanocarrier formulations to rescue ferroptosis, which can be applied to neurodegeneration, inflammation, liver damage, kidney disease, and more. Here, we present the synthesis,...

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Bibliographic Details
Published in:Biomacromolecules 2024-02, Vol.25 (2), p.1068-1083
Main Authors: Morrow, Joshua P., Mazrad, Zihnil A. I., Warne, Nicole M., Ayton, Scott, Bush, Ashley I., Kempe, Kristian
Format: Article
Language:English
Subjects:
Antigens
Cell Line
Humans
Micelles
Neuroblastoma
Oxazoles
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Summary:A great deal of nanocarriers have been applied to induce ferroptosis in cancer research, yet there are limited examples of nanocarrier formulations to rescue ferroptosis, which can be applied to neurodegeneration, inflammation, liver damage, kidney disease, and more. Here, we present the synthesis, characterization, and in vitro evaluation of pH-responsive, core-cross-linked micelle (CCM) ferrostatin-1 (Fer-1) conjugates with amine, valproic acid, and biotin surface chemistries. Fer-1 release from stable and defined CCM Fer-1 conjugates was quantified, highlighting the sustained release for 24 h. CCM Fer-1 conjugates demonstrated excellent ferroptosis rescue by their antilipid peroxidation activity in a diverse set of cell lines in vitro. Additionally, CCMs showed tunable cell association in SH-SY5Y and translocation across an in vitro blood–brain barrier (BBB) model, highlighting potential brain disease applications. Overall, here, we present a polymeric Fer-1 delivery system to enhance Fer-1 action, which could help in improving Fer-1 action in the treatment of ferroptosis-related diseases.
ISSN:1525-7797
1526-4602
1526-4602
DOI:10.1021/acs.biomac.3c01106