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This allows the loading capacity of MOFs for small-molecule drugs to be readily tailored by rationally adjusting their structures and physicochemical properties. Furthermore, the introduction of additional functional groups into MOFs can enable the stimuli-responsive release of small-molecule drugs, thus rendering MOFs promising candidates for small-molecule drug delivery. With this perspective, we summarize the advances in the construction of MOF-based small-molecule drug delivery carriers and analyze the advantages and limitations of the various loading strategies for small-molecule drugs. We also introduce drug release mechanisms and their application for the targeted treatment of various human diseases. In particular, this perspective describes how the corresponding drug-loading strategies should be selected based on the inherent physicochemical properties of the small-molecule drugs and the specific biomedical application, in order to facilitate clinical translation.<\/jats:p>","DOI":"10.1021\/jacs.6c06915","type":"journal-article","created":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T17:02:36Z","timestamp":1786640556000},"page":"35216-35232","source":"Crossref","is-referenced-by-count":1,"title":["Metal\u2013Organic\nFrameworks (MOFs) for the Delivery\nof Small-Molecule Therapeutics"],"prefix":"10.1021","volume":"148","author":[{"given":"Pei-Hong","family":"Tong","sequence":"first","affiliation":[{"name":"East China University of Science and Technology , , 130 Meilong Rd , ,","place":["Shanghai, China, 200237"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xi-Le","family":"Hu","sequence":"additional","affiliation":[{"name":"East China University of Science and Technology , , 130 Meilong Rd , ,","place":["Shanghai, China, 200237"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai-Cheng","family":"Yan","sequence":"additional","affiliation":[{"name":"East China University of Science and Technology , , 130 Meilong Rd , ,","place":["Shanghai, China, 200237"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Shuai","family":"Yuan","sequence":"additional","affiliation":[{"name":"Tongji University , , No. 507 Zhengmin Road , ,","place":["Shanghai, China, 200433"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4095-2191","authenticated-orcid":true,"given":"Tony D.","family":"James","sequence":"additional","affiliation":[{"name":"University of Bath , , ,","place":["Bath, U.K., BA2 7AY"]},{"name":"Henan Normal University , , ,","place":["Xinxiang, China, 453007"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4709-3334","authenticated-orcid":true,"given":"Hong-Yang","family":"Wang","sequence":"additional","affiliation":[{"name":"Eastern Hepatobiliary Surgery Hospital , , ,","place":["Shanghai, China, 200438"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8736-3511","authenticated-orcid":true,"given":"Xiao-Peng","family":"He","sequence":"additional","affiliation":[{"name":"East China University of Science and Technology , , 130 Meilong Rd , ,","place":["Shanghai, China, 200237"]},{"name":"Eastern Hepatobiliary Surgery Hospital , , ,","place":["Shanghai, China, 200438"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,8,13]]},"reference":[{"issue":"5","key":"2026090104500432000_cit1","doi-asserted-by":"publisher","first-page":"661","DOI":"10.3390\/ph17050661","article-title":"Small molecule drugs targeting viral\npolymerases","volume":"17","author":"Palazzotti","year":"2024","journal-title":"Pharmaceuticals"},{"key":"2026090104500432000_cit2","doi-asserted-by":"publisher","first-page":"116706","DOI":"10.1016\/j.ejmech.2024.116706","article-title":"A comprehensive review\nof small molecule drugs approved by the FDA\nin 2023: Advances and prospects","volume":"276","author":"Bai","year":"2024","journal-title":"Eur. 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