{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T02:02:36Z","timestamp":1793844156157,"version":"4.6.1"},"reference-count":39,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2024,8,27]],"date-time":"2024-08-27T00:00:00Z","timestamp":1724716800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH","award":["R00DE025915"],"award-info":[{"award-number":["R00DE025915"]}]},{"name":"NIH","award":["R03DE028026"],"award-info":[{"award-number":["R03DE028026"]}]},{"name":"NIH","award":["R01CA288366"],"award-info":[{"award-number":["R01CA288366"]}]},{"name":"NIH","award":["R01DE027901"],"award-info":[{"award-number":["R01DE027901"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>5-fluorouracil (5-FU), a chemotherapeutic agent against oral squamous cell carcinoma (OSCC), is limited by poor pharmacokinetics and toxicity. The pH-sensitive zeolite imidazolate framework-8 (ZIF-8) may increase the selectivity and length of 5-FU released into the acidic tumor microenvironment. This study examined the in vitro 5-FU absorption and release profiles of ZIF-8, and then progressed to cytotoxicity assays using the OSCC primary cell line SCC7. The 5-FU loading capacity of ZIF-8 was calculated with UV-vis spectroscopy (\u03bb = 260 nm). 5-FU release was quantified by submerging 5-FU@ZIF-8 in pH 7.4 and 5.5 acetate buffer over 48 h. For the cytotoxicity assays, 5-FU, ZIF-8, and 5-FU@ZIF-8 were added to SCC7 cultures at 25, 50, and 100 \u03bcg\/mL. Cell viability was assessed through toluidine blue staining and further quantified through transcriptomic RNA sequencing. ZIF-8 stabilized at a maximum absorption of 2.71 \u00b1 0.22 mg 5-FU, and released 0.66 mg more 5-FU at pH 5.5 than 7.4 for at least 72 h. The cytotoxicity assays showed that 5-FU@ZIF-8 had a synergistic inhibitory effect at 50 \u03bcg\/mL. The RNA sequencing analysis further revealed the molecular targets of 5-FU@ZIF-8 in SCC7. 5-FU@ZIF-8 may release 5-FU based on the pH of the surrounding microenvironments and synergistically inhibit OSCC.<\/jats:p>","DOI":"10.3390\/ijms25179292","type":"journal-article","created":{"date-parts":[[2024,8,27]],"date-time":"2024-08-27T09:26:51Z","timestamp":1724750811000},"page":"9292","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["ZIF-8 as a pH-Responsive Nanoplatform for 5-Fluorouracil Delivery in the Chemotherapy of Oral Squamous Cell Carcinoma"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9741-3113","authenticated-orcid":false,"given":"Jessica","family":"Hao","sequence":"first","affiliation":[{"name":"School of Dental Medicine, University of Pennsylvania, Philadelphia, PA 19019, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2899-1208","authenticated-orcid":false,"given":"Chider","family":"Chen","sequence":"additional","affiliation":[{"name":"Oral and Maxillofacial Surgery, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7706-6858","authenticated-orcid":false,"given":"Kresimir","family":"Pavelic","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Juraj Dobrila University of Pula, 52100 Pula, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fusun","family":"Ozer","sequence":"additional","affiliation":[{"name":"Preventative and Restorative Sciences, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,8,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1159\/000485322","article-title":"High-Risk Human Papillomavirus in Oral Cancer: Clinical Implications","volume":"94","author":"Yete","year":"2018","journal-title":"Oncology"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Porcheri, C., and Mitsiadis, T.A. 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