{"doi":"10.1002/ange.202302303","title":"Enzyme‐Triggered Chemodynamic Therapy via a Peptide‐H <sub>2</sub> S Donor Conjugate with Complexed Fe <sup>2+</sup>","abstract":"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.","journal":"Angewandte Chemie","year":2023,"id":388139,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9569,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1029448,"name":"William R. Archer","orcid":"0000-0002-6326-6602","position":1,"is_corresponding":false},{"id":1030153,"name":"Katlyn F. Morales","orcid":null,"position":2,"is_corresponding":false},{"id":1029449,"name":"Michael D. Schulz","orcid":"0000-0001-8499-6025","position":3,"is_corresponding":false},{"id":304538,"name":"Yin Wang","orcid":"0000-0001-6729-7230","position":4,"is_corresponding":false},{"id":304541,"name":"John B. Matson","orcid":"0000-0001-7984-5396","position":5,"is_corresponding":false},{"id":1029447,"name":"Yumeng Zhu","orcid":"0000-0002-3727-3008","position":0,"is_corresponding":true}],"reference_count":41,"raw_metadata":null,"created_at":"2026-07-19T01:18:13.977537Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}