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Due to low bioavailability and passive targetability of anticancer drugs show great limitations in cancer therapy, the treatment of OSCC faces major challenges. Folic acid (FA) targeting can deliver anticancer drugs efficiently into the tumor environment, further enhance the anti-cancer efficacy. Herein, the nanoplatform based on UiO-66 that encapsulated with an effective FA targeting ligands and the pH-responsive polyethylene glycol (PEG) layer for the targeted delivery of berberine (Ber) is constructed for fighting against OSCC. The FA modification and controlled pH-responsiveness enable the targeted delivery of UiO-66\/PEG-FA, which promotes the release of Ber and increases the cumulative intracellular Ber concentration, which both promote consumption of glutathione (GSH) and induced generation of reactive oxygen species (ROS), further stimulate the secretion of inflammatory factors (TNF-<jats:italic>\u03b1<\/jats:italic> and IL-1<jats:italic>\u03b2<\/jats:italic>). A comprehensive evaluation of <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic> experiments show that UiO-66@Ber\/PEG-FA promote autophagy and apoptosis of tumor cells by regulating the expression of Beclin-1, ATG13, BAX and Bcl-2, and effectively inhibit tumor growth. Overall, UiO-66@Ber\/PEG-FA exhibit superior pH-responsiveness and targeted therapeutic efficiencies <jats:italic>in vitro<\/jats:italic> and vivo, it can serve as an approach for OSCC therapy.<\/jats:p>","DOI":"10.1088\/1758-5090\/add9d2","type":"journal-article","created":{"date-parts":[[2025,5,16]],"date-time":"2025-05-16T22:51:36Z","timestamp":1747435896000},"page":"035012","update-policy":"https:\/\/doi.org\/10.1088\/crossmark-policy","source":"Crossref","is-referenced-by-count":11,"title":["Multifunctional nanoplatform based on polyethylene glycol-folic acid modified UiO-66 (Zr) as drug delivery platform for enhanced therapy of cancer"],"prefix":"10.1088","volume":"17","author":[{"given":"Mengyuan","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaming","family":"Ge","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingwen","family":"Yao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanhao","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheng","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangli","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3316-2535","authenticated-orcid":true,"given":"Fei","family":"Tian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-1267-826X","authenticated-orcid":true,"given":"Jing","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"266","published-online":{"date-parts":[[2025,5,27]]},"reference":[{"key":"bfadd9d2bib1","doi-asserted-by":"publisher","first-page":"S51","DOI":"10.1016\/j.jobcr.2016.07.003","article-title":"Muthumeenakshi, Salivary biomarkers in oral squamous cell carcinoma\u2014an insight","volume":"6","author":"Radhika","year":"2016","journal-title":"J. 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