TY - JOUR
T1 - Schiff-Base Cross-Linked Poly(2-oxazoline) Micelle Drug Conjugates Possess Antiferroptosis Activity in Numerous In Vitro Cell Models
AU - Morrow, Joshua P.
AU - Mazrad, Zihnil A.I.
AU - Warne, Nicole M.
AU - Ayton, Scott
AU - Bush, Ashley I.
AU - Kempe, Kristian
N1 - Funding Information:
J.P.M. and N.M.W. wish 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 acknowledges the award of an ARC Future Fellowship (FT190100572) from the Australian Research Council (ARC). A.I.B. was supported by the Australian National Health and Medical Research Council (GNT1194028). The authors would like to acknowledge the Boyd group at MIPS for their advice and guidance on drug release modeling and use of their equipment. The authors also thank Dr. Joseph A. Nicolazzo for use of their equipment in the development of in vitro BBB model.
Publisher Copyright:
© 2024 American Chemical Society
PY - 2024/2/12
Y1 - 2024/2/12
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85182009398&partnerID=8YFLogxK
U2 - 10.1021/acs.biomac.3c01106
DO - 10.1021/acs.biomac.3c01106
M3 - Article
C2 - 38178625
AN - SCOPUS:85182009398
SN - 1525-7797
VL - 25
SP - 1068
EP - 1083
JO - Biomacromolecules
JF - Biomacromolecules
IS - 2
ER -
