{"doi":"10.1016/j.matdes.2025.115274","title":"Novel stable “sandwich” cyclodextrin inclusion of a lipophilic S-nitrosothiol for controlled delivery of nitric oxide","abstract":"Nitric oxide (NO) is a versatile biological signaling molecule with applications in antimicrobial, anticancer, and cardiovascular therapies. A newly developed NO donor, S-nitroso-1-adamantane thiol (SNAT), has previously demonstrated excellent antithrombogenic and antimicrobial properties when impregnated into PVC tubing of extracorporeal circuits. However, the hydrophobicity of SNAT and its storage stability remain a major challenge for further biomedical applications. Here, we report a novel NO delivery system based on the inclusion of the highly lipophilic SNAT within hydroxypropyl-β-cyclodextrin (CD), forming a stable \"sandwich\" cyclodextrin inclusion complex (CD-SNAT). Spectroscopic, structural, and morphological characterization confirmed successful SNAT inclusion in the CD cavity. The CD-SNAT complex showed excellent aqueous solubility, and remarkable aqueous stability at physiological pH, even resistant to trace amounts of transition metal ions, which are detrimental to common S-nitrosothiols, like S-nitroso-N-acetyl-penicillamine. NO release could be efficiently triggered by endogenous free thiols like cysteine, or UV light. Sustained and cysteine-induced NO release from CD-SNAT was confirmed by chemiluminescence. Intracellular NO delivery from SNAT was visualized in melanoma cells in the presence of cysteine. Remarkably, the solid complex remained >90% intact after six-month storage at room temperature. Hence, CD-SNAT provides a stable, tunable, biocompatible platform for controlled NO delivery, with promising biomedical applications.","journal":"Materials & Design","year":2025,"id":529489,"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":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9487,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1408780,"name":"Partha S. Sheet","orcid":null,"position":1,"is_corresponding":false},{"id":1408332,"name":"Kai‐Kai Wang","orcid":"0000-0002-6594-9570","position":2,"is_corresponding":false},{"id":1357489,"name":"Hannah J. Naldrett","orcid":null,"position":3,"is_corresponding":false},{"id":1408781,"name":"Lautner-Csorba Orsolya","orcid":null,"position":4,"is_corresponding":false},{"id":488568,"name":"Steven P. Schwendeman","orcid":"0000-0003-3470-624X","position":5,"is_corresponding":false},{"id":1062954,"name":"Gergely Lautner","orcid":"0000-0001-7519-2391","position":6,"is_corresponding":false},{"id":1408331,"name":"Xinyao Wang","orcid":"0009-0008-8194-5669","position":0,"is_corresponding":true}],"reference_count":71,"raw_metadata":null,"created_at":"2026-07-19T02:50:56.971987Z","pmid":"41647439","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":[]}