In:
Angewandte Chemie, Wiley, Vol. 135, No. 22 ( 2023-05-22)
Abstract:
Inducing high levels of reactive oxygen species (ROS) inside tumor cells is a cancer therapy method termed chemodynamic therapy (CDT). Relying on delivery of Fenton reaction promoters such as Fe 2+ , CDT takes advantage of overproduced ROS in the tumor microenvironment. We developed a peptide‐H 2 S donor conjugate, complexed with Fe 2+ , termed AAN ‐ PTC – Fe 2+ . The AAN tripeptide was specifically cleaved by legumain, an enzyme overexpressed in glioma cells, to release carbonyl sulfide (COS). Hydrolysis of COS by carbonic anhydrase formed H 2 S, an inhibitor of catalase, an enzyme that detoxifies H 2 O 2 . Fe 2+ and H 2 S together increased intracellular ROS levels and decreased viability in C6 glioma cells compared with controls lacking either Fe 2+ , the AAN sequence, or the ability to generate H 2 S. AAN ‐ PTC – Fe 2+ performed better than temezolimide while exhibiting no cytotoxicity toward H9C2 cardiomyocytes. This study provides an H 2 S‐amplified, enzyme‐responsive platform for synergistic cancer treatment.
Type of Medium:
Online Resource
ISSN:
0044-8249
,
1521-3757
DOI:
10.1002/ange.v135.22
DOI:
10.1002/ange.202302303
Language:
English
Publisher:
Wiley
Publication Date:
2023
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