Dataset Information

Enzyme-Triggered Chemodynamic Therapy via a Peptide-H₂ S Donor Conjugate with Complexed Fe².

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 Fe²⁺ , CDT takes advantage of overproduced ROS in the tumor microenvironment. We developed a peptide-H₂ S donor conjugate, complexed with Fe²⁺ , termed AAN-PTC-Fe²⁺ . 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 H₂ S, an inhibitor of catalase, an enzyme that detoxifies H₂ O₂ . Fe²⁺ and H₂ S together increased intracellular ROS levels and decreased viability in C6 glioma cells compared with controls lacking either Fe²⁺ , the AAN sequence, or the ability to generate H₂ S. AAN-PTC-Fe²⁺ performed better than temezolimide while exhibiting no cytotoxicity toward H9C2 cardiomyocytes. This study provides an H₂ S-amplified, enzyme-responsive platform for synergistic cancer treatment.

SUBMITTER: Zhu Y

PROVIDER: S-EPMC10241505 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Enzyme-Triggered Chemodynamic Therapy via a Peptide-H2 S Donor Conjugate with Complexed Fe2.

Zhu Yumeng Y Archer William R WR Morales Katlyn F KF Schulz Michael D MD Wang Yin Y Matson John B JB

Angewandte Chemie (International ed. in English) 20230420 22

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 Fe2+ , CDT takes advantage of overproduced ROS in the tumor microenvironment. We developed a peptide-H2 S donor conjugate, complexed with Fe2+ , termed AAN-PTC-Fe2+ . The AAN tripeptide was specifically cleaved by legumain, an enzyme overexpressed in glioma cells, ...[more]

PMID: 37078735

Similar Datasets

Project description:Rationale: Chemodynamic therapy (CDT) based on the Fe(II)-mediated Fenton reaction is an emerging tumor treatment strategy. However, the catalytic efficiency in tumors is crucially limited by Fe(II). Herein, an endogenous hydrogen sulfide (H2S) accelerated Fe(III)/Fe(II) transformation and photothermal synergistically enhanced CDT strategy based on ellagic acid-Fe-bovine serum albumin (EA-Fe@BSA) nanoparticles (NPs) was developed for colon tumor inhibition. On the one hand, the Fe(III) with low catalytic activity in the EA-Fe@BSA NPs could be rapidly reduced to the highly active Fe(II) by the abundant H2S in colon cancer tissues. Thus, a rapid Fe(III)/Fe(II) conversion system was established, wherein highly active Fe(II) ions were continuously regenerated to improve the CDT efficiency. On the other hand, the photothermal effect of EA-Fe@BSA NPs also accelerated the production of hydroxyl radicals (•OH), thereby synergistically enhancing the CDT performance and improving the therapeutic efficacy. Methods: The endogenous H2S accelerated Fe(III)/Fe(II) conversion and PTT enhanced CDT were investigated by characterization of the Fe valence state and detection of •OH. T 1-weighted magnetic resonance imaging (MRI) was tested both in vitro and in vivo. The biocompatibility of NPs were examined via MTT assay, hemolysis analysis and routine blood measurements. The enhanced CDT was investigated in HCT116 colon cancer cells by Calcein-AM/PI staining and MTT assay, and tumor inhibition was demonstrated in HCT116 tumor bearing mice. Results: In this work, EA-Fe@BSA NPs were constructed as a CDT theranostic reagent. The H2S accelerated Fe(III)/Fe(II) conversion was confirmed, more degradation of MB and generation of •OH demonstrated the enhanced CDT in vitro. EA-Fe@BSA NPs exhibited good T 1-weighted MRI performance. More importantly, it displayed strong near-infrared (NIR) absorption and excellent photothermal efficiency, further promotes the production of •OH. Hence, the efficacy of CDT was enhanced, and the tumor growth was inhibited efficiently. Conclusion: All results demonstrate that this strategy based on endogenous H2S promoted Fe(III)/Fe(II) transformation together with PTT acceleration permits efficient Fenton-reaction- mediated CDT both in vitro and in vivo, which holds great potential for effective colon cancer theranostics.

Dataset Information

Enzyme-Triggered Chemodynamic Therapy via a Peptide-H₂ S Donor Conjugate with Complexed Fe².

Publications

Enzyme-Triggered Chemodynamic Therapy via a Peptide-H<sub>2</sub> S Donor Conjugate with Complexed Fe<sup>2</sup>.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets