{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,12]],"date-time":"2026-11-12T04:16:47Z","timestamp":1794457007581,"version":"4.9.1"},"reference-count":102,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2022,2,11]],"date-time":"2022-02-11T00:00:00Z","timestamp":1644537600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministero degli Esteri e della Cooperazione Internazionale MAECI grant","award":["MAE00691612020-06-26"],"award-info":[{"award-number":["MAE00691612020-06-26"]}]},{"name":"IMI EU Grants Investigating Mechanisms and Models predictive of accessibility of therapeutics (IM2PACT) Into the Brain IMI2","award":["n.807015(im2pact.org)"],"award-info":[{"award-number":["n.807015(im2pact.org)"]}]},{"name":"POR-FESR Project (European Funding for the Regional Development): \u201cMAT2REP","award":["2019-2021"],"award-info":[{"award-number":["2019-2021"]}]},{"name":"GLIOSILK Project (Reference Number: EURONANOMED2019-075","award":["EURONANOMED2019-075"],"award-info":[{"award-number":["EURONANOMED2019-075"]}]},{"name":"FAR Unimore Fondazione di Modena Nano-immuno targeting per il trattamento del glioblastoma multiforme Acronimo: NIT Project","award":["01"],"award-info":[{"award-number":["01"]}]},{"name":"Creutzfeldt\u2013Jakob disease Foundation","award":["01"],"award-info":[{"award-number":["01"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Polymers"],"abstract":"<jats:p>Reactive oxygen species (ROS)-sensitive drug delivery systems (DDS) specifically responding to altered levels of ROS in the pathological microenvironment have emerged as an effective means to enhance the pharmaceutical efficacy of conventional nanomedicines, while simultaneously reducing side effects. In particular, the use of the biocompatible, biodegradable, and non-toxic ROS-responsive thioketal (TK) functional group in the design of smart DDS has grown exponentially in recent years. In the design of TK-based DDS, different technological uses of TK have been proposed to overcome the major limitations of conventional DDS counterparts including uncontrolled drug release and off-target effects. This review will focus on the different technological uses of TK-based biomaterials in smart nanomedicines by using it as a linker to connect a drug on the surface of nanoparticles, form prodrugs, as a core component of the DDS to directly control its structure, to control the opening of drug-releasing gates or to change the conformation of the nano-systems. A comprehensive view of the various uses of TK may allow researchers to exploit this reactive linker more consciously while designing nanomedicines to be more effective with improved disease-targeting ability, providing novel therapeutic opportunities in the treatment of many diseases.<\/jats:p>","DOI":"10.3390\/polym14040687","type":"journal-article","created":{"date-parts":[[2022,2,14]],"date-time":"2022-02-14T03:46:00Z","timestamp":1644810360000},"page":"687","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":169,"title":["Applications of the ROS-Responsive Thioketal Linker for the Production of Smart Nanomedicines"],"prefix":"10.3390","volume":"14","author":[{"given":"Arianna","family":"Rinaldi","sequence":"first","affiliation":[{"name":"Nanotech Lab, Te.Far.T.I., Department Life Sciences, University of Modena and Reggio Emilia, 41125 Modena, Italy"},{"name":"Clinical and Experimental Medicine PhD Program, University of Modena and Reggio Emilia, 41125 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riccardo","family":"Caraffi","sequence":"additional","affiliation":[{"name":"Nanotech Lab, Te.Far.T.I., Department Life Sciences, University of Modena and Reggio Emilia, 41125 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Vittoria","family":"Grazioli","sequence":"additional","affiliation":[{"name":"Nanotech Lab, Te.Far.T.I., Department Life Sciences, University of Modena and Reggio Emilia, 41125 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia","family":"Oddone","sequence":"additional","affiliation":[{"name":"Nanotech Lab, Te.Far.T.I., Department Life Sciences, University of Modena and Reggio Emilia, 41125 Modena, Italy"},{"name":"Redox Biology of Trypanosomes, Institut Pasteur de Montevideo, Mataojo 2020, Montevideo 11400, Uruguay"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luciana","family":"Giardino","sequence":"additional","affiliation":[{"name":"Interdepartmental Center for Industrial Research in Life Sciences and Technologies, University of Bologna, 40064 Bologna, Italy"},{"name":"Department of Veterinary Medical Science, University of Bologna, 40064 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8318-667X","authenticated-orcid":false,"given":"Giovanni","family":"Tosi","sequence":"additional","affiliation":[{"name":"Nanotech Lab, Te.Far.T.I., Department Life Sciences, University of Modena and Reggio Emilia, 41125 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Angela","family":"Vandelli","sequence":"additional","affiliation":[{"name":"Nanotech Lab, Te.Far.T.I., Department Life Sciences, University of Modena and Reggio Emilia, 41125 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Calz\u00e0","sequence":"additional","affiliation":[{"name":"Interdepartmental Center for Industrial Research in Life Sciences and Technologies, University of Bologna, 40064 Bologna, Italy"},{"name":"Department of Pharmacy and BioTechnology, University of Bologna, 40127 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2400-9910","authenticated-orcid":false,"given":"Barbara","family":"Ruozi","sequence":"additional","affiliation":[{"name":"Nanotech Lab, Te.Far.T.I., Department Life Sciences, University of Modena and Reggio Emilia, 41125 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2204-1981","authenticated-orcid":false,"given":"Jason Thomas","family":"Duskey","sequence":"additional","affiliation":[{"name":"Nanotech Lab, Te.Far.T.I., Department Life Sciences, University of Modena and Reggio Emilia, 41125 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,2,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1186\/s12951-018-0392-8","article-title":"Nano Based Drug Delivery Systems: Recent Developments and Future Prospects","volume":"16","author":"Patra","year":"2018","journal-title":"J. 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