{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T15:59:19Z","timestamp":1791302359401,"version":"4.1.0"},"reference-count":58,"publisher":"American Chemical Society (ACS)","issue":"39","license":[{"start":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T00:00:00Z","timestamp":1789862400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["R01CA258421-01"],"award-info":[{"award-number":["R01CA258421-01"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,10,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Thiolated chitosan nanoparticles (TCNs) are versatile biomaterials with applications in tissue engineering, coatings, wound healing, and drug delivery. Their biodegradability and ability to conjugate sulfhydryl-containing payloads make TCNs attractive as carriers for controlled therapeutic delivery. However, the nanodelivery of metallodrugs remains challenging because of instability and premature ligand exchange under physiological conditions. Developing robust strategies that enable the delivery of intact metal-based therapeutics is, therefore, of significant interest. Here, we exploit the redox properties of a gold(III)-dithiocarbamate complex (AuDCN1) to enable the covalent attachment of its sulfhydryl ligand to the thiolated chitosan polymer backbone through disulfide bond formation. Nanoparticles were subsequently prepared via an ionic gelation method to generate AuDCN1-conjugated thiolated chitosan nanoparticles (Au-TCNs). Cargo release was characterized by LC\u2013MS and spectroscopic methods under reducing conditions triggered by l-glutathione, a biologically relevant nucleophile. Biological evaluation demonstrated that Au-TCN nanoparticles exhibit potent activity against triple-negative breast cancer cells, inducing mitochondrial dysfunction through depolarization of the mitochondrial membrane potential and increased levels of mitochondrial reactive oxygen species production. Furthermore, Au-TCN significantly inhibited mammosphere formation in a three-dimensional culture, indicating activity against stem-like tumor cell populations. Collectively, these results highlight thiolated chitosan nanoparticles as a promising redox-responsive platform for delivering gold-based metallodrugs, expanding therapeutic strategies for the treatment of triple-negative breast cancer.<\/jats:p>","DOI":"10.1021\/acsomega.6c01689","type":"journal-article","created":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T14:01:42Z","timestamp":1789912902000},"page":"58676-58685","source":"Crossref","is-referenced-by-count":0,"title":["Delivery of Anticancer\nGold-Dithiocarbamate via Thiolated\nChitosan Nanoparticles"],"prefix":"10.1021","volume":"11","author":[{"given":"Maame Abena O.","family":"Afrifa","sequence":"first","affiliation":[{"name":"University of Kentucky , , , ,","place":["Lexington, Kentucky, United States, 40506"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jovita O.","family":"Daraezinwa","sequence":"additional","affiliation":[{"name":"University of Kentucky , , , ,","place":["Lexington, Kentucky, United States, 40506"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4947-7283","authenticated-orcid":true,"given":"Samuel G.","family":"Awuah","sequence":"additional","affiliation":[{"name":"University of Kentucky , , , ,","place":["Lexington, Kentucky, United States, 40506"]},{"name":"University of Kentucky , , , ,","place":["Lexington, Kentucky, United States, 40536"]},{"name":"University of Kentucky Markey Cancer Center , , ,","place":["Lexington, KY, United States, 40536"]},{"name":"University of Kentucky Bioelectronics and Nanomedicine Research Center , , ,","place":["Lexington, KY, United States, 40506"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,9,20]]},"reference":[{"key":"2026100610475924200_cit1","doi-asserted-by":"publisher","first-page":"121689","DOI":"10.1016\/j.carbpol.2023.121689","article-title":"Thiolated chitosan encapsulation constituted mucoadhesive nanovaccine\nconfers broad protection against divergent influenza A viruses","volume":"328","author":"Ding","year":"2024","journal-title":"Carbohydr. Polym."},{"issue":"6","key":"2026100610475924200_cit2","doi-asserted-by":"publisher","first-page":"854","DOI":"10.3390\/pharmaceutics13060854","article-title":"Thiolated-polymer-based\nnanoparticles as an avant-garde\napproach for anticancer therapies\u2500reviewing thiomers from chitosan\nand hyaluronic acid","volume":"13","author":"Grosso","year":"2021","journal-title":"Pharmaceutics"},{"issue":"34","key":"2026100610475924200_cit3","doi-asserted-by":"publisher","first-page":"40304","DOI":"10.1021\/acsami.3c09337","article-title":"S-Protected Thiolated Chitosan versus Thiolated Chitosan\nas Cell\nAdhesive Biomaterials for Tissue Engineering","volume":"15","author":"Le-Vinh","year":"2023","journal-title":"ACS Appl. Mater. 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Compos."},{"key":"2026100610475924200_cit6","doi-asserted-by":"publisher","first-page":"135363","DOI":"10.1016\/j.colsurfa.2024.135363","article-title":"Mucoadhesive and drug\nrelease of cholic acid based thiomeric micelles\nand encapsulated silver and gold nanoparticles for anticancer studies","volume":"703","author":"Baskaran","year":"2024","journal-title":"Colloids Surf., A"},{"issue":"9","key":"2026100610475924200_cit7","doi-asserted-by":"publisher","first-page":"755","DOI":"10.2217\/nnm-2023-0318","article-title":"pH-sensitive docetaxel-loaded\nchitosan\/thiolated hyaluronic acid\npolymeric nanoparticles for colorectal cancer","volume":"19","author":"Noreen","year":"2024","journal-title":"Nanomedicine"},{"issue":"1","key":"2026100610475924200_cit8","doi-asserted-by":"publisher","first-page":"211","DOI":"10.3390\/pharmaceutics15010211","article-title":"The progress of chitosan-based\nnanoparticles for intravesical bladder\ncancer treatment","volume":"15","author":"Yu","year":"2023","journal-title":"Pharmaceutics"},{"issue":"5","key":"2026100610475924200_cit9","doi-asserted-by":"publisher","first-page":"2181","DOI":"10.1021\/acsbiomaterials.2c01297","article-title":"Chitosan derivatives as carriers for drug delivery\nand biomedical\napplications","volume":"9","author":"Manna","year":"2023","journal-title":"ACS Biomater. 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Mater.\nInterfaces"},{"key":"2026100610475924200_cit32","doi-asserted-by":"publisher","first-page":"119375","DOI":"10.1016\/j.ica.2019.119375","article-title":"Exploring six-coordinate germanium\n(IV)-diketonate complexes as anticancer agents","volume":"503","author":"Mertens","year":"2020","journal-title":"Inorg. Chim. Acta"},{"issue":"10","key":"2026100610475924200_cit33","doi-asserted-by":"publisher","first-page":"6612","DOI":"10.1021\/acs.chemrev.2c00649","article-title":"Next Generation Gold\nDrugs and Probes: Chemistry and Biomedical Applications","volume":"123","author":"Mertens","year":"2023","journal-title":"Chem. Rev."},{"issue":"13","key":"2026100610475924200_cit34","doi-asserted-by":"publisher","first-page":"5518","DOI":"10.1039\/D1CS00933H","article-title":"Recent development of gold (I) and gold (III) complexes\nas therapeutic\nagents for cancer diseases","volume":"51","author":"Lu","year":"2022","journal-title":"Chem. Soc. 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Bio Mater."},{"key":"2026100610475924200_cit37","doi-asserted-by":"publisher","first-page":"104340","DOI":"10.1016\/j.isci.2022.104340","article-title":"Gold (III)-P-chirogenic complex induce mitochondrial dysfunction\nin triple-negative breast cancer","volume":"25","author":"Olelewe","year":"2022","journal-title":"iScience"},{"issue":"1","key":"2026100610475924200_cit38","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1007\/s12032-023-02257-6","article-title":"Emerging\ntreatment approaches for triple-negative\nbreast cancer","volume":"41","author":"Capuozzo","year":"2023","journal-title":"Med. Oncol."},{"key":"2026100610475924200_cit39","doi-asserted-by":"publisher","first-page":"1405491","DOI":"10.3389\/fonc.2024.1405491","article-title":"Advancements\nand challenges in triple-negative breast\ncancer: A comprehensive review of therapeutic and diagnostic strategies","volume":"14","author":"Xiong","year":"2024","journal-title":"Front. 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