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In this work, a nano-sized biocompatible metal\u2013organic framework (MOF), Mg(H2TBAPy)(H2O)3\u00b7C4H8O2 (TDL-Mg), was constructed by employing \u03c0-conjugated 1,3,6,8-tetrakis(p-benzoic acid)pyrene (H4TBAPy) as a ligand and used for 5-fluorouracil (5-FU) loading (28.2 wt %) and sustained slow release. TDL-Mg exhibits a 3D supramolecular architecture featuring a 1D rectangle channel with a size of 6.2 \u00d7 8.1 \u00c52 and a Brunauer\u2013Emmett\u2013Teller surface area of 627 m2\u00b7g\u20131. Channel microenvironment analysis shows that the rigid H2TBAPy2\u2013 ligand adopts special torsion to stabilize the channels and offer rich \u03c0-binding sites; the partially deprotonated carboxyls not only participate in the formation of strong hydrogen bonds but also create a mild pH buffer environment for biological applications. Suitable host\u2013guest interactions are generated by the synergistic effect of polydirectional hydrogen bonds, multiple \u03c0-interactions, and confined channels, which allow 5-FU@TDL-Mg to release 76% of load in 72 h, a medically reasonable rate. Microcalorimetry was used to directly quantify these host\u2013guest interactions with a moderate enthalpy of 22.3 kJ\u00b7mol\u20131, which provides a distinctive thermodynamic interpretation for understanding the relationship between the MOF design and the drug release rate. Additionally, the nano-sized 5-FU@TDL-Mg can be taken up by mouse breast cancer cells (4T1 cells) for imaging based on the dramatic fluorescence change during the release of 5-FU, exhibiting potential applications in biological systems.<\/jats:p>","DOI":"10.1021\/acsami.0c01198","type":"journal-article","created":{"date-parts":[[2020,2,27]],"date-time":"2020-02-27T10:03:03Z","timestamp":1582797783000},"page":"14914-14923","source":"Crossref","is-referenced-by-count":55,"title":["A\nLuminescent Mg-Metal\u2013Organic Framework for Sustained Release\nof 5-Fluorouracil: Appropriate Host\u2013Guest Interaction\nand Satisfied Acid\u2013Base Resistance"],"prefix":"10.1021","volume":"12","author":[{"given":"Zengchi","family":"Hu","sequence":"first","affiliation":[{"name":"Northwest University , , ,","place":["Xi\u2019an, China, 710127"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengfang","family":"Qiao","sequence":"additional","affiliation":[{"name":"Shangluo University , , ,","place":["Shangluo, China, 726000"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9342-8422","authenticated-orcid":true,"given":"Zhengqiang","family":"Xia","sequence":"additional","affiliation":[{"name":"Northwest University , , ,","place":["Xi\u2019an, China, 710127"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Li","sequence":"additional","affiliation":[{"name":"Northwest University , , ,","place":["Xi\u2019an, China, 710127"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Han","sequence":"additional","affiliation":[{"name":"Northwest University , , ,","place":["Xi\u2019an, China, 710127"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Wei","sequence":"additional","affiliation":[{"name":"Northwest University , , ,","place":["Xi\u2019an, China, 710127"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Yang","sequence":"additional","affiliation":[{"name":"Northwest University , , ,","place":["Xi\u2019an, China, 710127"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gang","family":"Xie","sequence":"additional","affiliation":[{"name":"Northwest University , , ,","place":["Xi\u2019an, China, 710127"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6851-7386","authenticated-orcid":true,"given":"Sanping","family":"Chen","sequence":"additional","affiliation":[{"name":"Northwest University , , ,","place":["Xi\u2019an, China, 710127"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengli","family":"Gao","sequence":"additional","affiliation":[{"name":"Northwest University , , ,","place":["Xi\u2019an, China, 710127"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2020,2,27]]},"reference":[{"key":"2026090301060956700_cit1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0078172","article-title":"New Insights into the RNA-Based Mechanism\nof Action of the Anticancer Drug 5\u2032-Fluorouracil in Eukaryotic\nCells","volume":"8","author":"Mojardi\u0301n","year":"2013","journal-title":"PLoS One"},{"key":"2026090301060956700_cit2","doi-asserted-by":"publisher","first-page":"513","DOI":"10.1016\/j.xphs.2017.10.012","article-title":"Fabrication and Use\nof Poly(D,L -lactide-co-glycolide)-Based Formulations Designed for\nModified Release of 5-Fluorouracil","volume":"107","author":"Leelakanok","year":"2018","journal-title":"J. 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