{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T16:21:08Z","timestamp":1787847668287,"version":"build-2784847793"},"reference-count":38,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T00:00:00Z","timestamp":1787788800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T00:00:00Z","timestamp":1787788800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["22377008"],"award-info":[{"award-number":["22377008"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["22327808"],"award-info":[{"award-number":["22327808"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["22507012"],"award-info":[{"award-number":["22507012"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Thiol\u2010mediated uptake (TMU) is a powerful strategy for promoting the cellular uptake of nano\u2010drugs; however, the mechanochemical principles that coupled\u00a0ligand reactivity, carrier mechanics, and receptor clustering remain poorly understood. Herein, the effect of carrier rigidity and cyclic disulfide reactivity on the thiol\u2010mediated cellular uptake of miRNA nano\u2010drugs was revealed. Compared with lipoic acid (LA), the higher enhancing effect of asparagusic acid (AspA) is identified with the greater affinity, higher binding stability, and more double\u2010disulfide binding. The greater association of AspA\u2010TFRC was also visualized by super\u2010resolution microscopy imaging. Molecular dynamics simulation further verified the superior membrane disruption and deeper insertion induced by AspA. However, both LA and AspA display concentration\u2010dependent self\u2010activation and self\u2010inhibition effects on exchanging with thiols. Furthermore, we provided direct evidence that thiolation can significantly accelerate endocytosis of rigid mesoporous silica nano\u2010drugs, whereas thiolation will shift the entry cell pathway of soft lipid nano\u2010drugs from endocytosis to membrane fusion, and AspA is more efficient. This work establishes a mechanochemical framework that links ligand reactivity, carrier mechanics, and receptor engagement to predict the cellular uptake mechanism of a thiol\u2010mediated nano\u2010drug delivery system.<\/jats:p>","DOI":"10.1002\/advs.77389","type":"journal-article","created":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T15:27:11Z","timestamp":1787844431000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Effect of Ligand Reactivity and Carrier Mechanics on Thiol\u2010Mediated Cellular Uptake for miRNA Nano\u2010Drugs"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-1482-1148","authenticated-orcid":false,"given":"Zhuang","family":"Zhang","sequence":"first","affiliation":[{"name":"College of Chemistry and Life Science Advanced Institute of Materials Science Changchun University of Technology  Changchun China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Chemistry and Life Science Advanced Institute of Materials Science Changchun University of Technology  Changchun China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Chemistry and Life Science Advanced Institute of Materials Science Changchun University of Technology  Changchun China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenkuan","family":"Cao","sequence":"additional","affiliation":[{"name":"College of Chemistry and Life Science Advanced Institute of Materials Science Changchun University of Technology  Changchun China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zehui","family":"Liu","sequence":"additional","affiliation":[{"name":"College of Chemistry and Life Science Advanced Institute of Materials Science Changchun University of Technology  Changchun China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-7328-9927","authenticated-orcid":false,"given":"Siying","family":"Li","sequence":"additional","affiliation":[{"name":"College of Chemistry and Life Science Advanced Institute of Materials Science Changchun University of Technology  Changchun China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4266-9012","authenticated-orcid":false,"given":"Hongda","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Electroanalytical Chemistry Changchun Institute of Applied Chemistry Chinese Academy of Sciences  Changchun China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3827-7123","authenticated-orcid":false,"given":"Yuping","family":"Shan","sequence":"additional","affiliation":[{"name":"College of Chemistry and Life Science Advanced Institute of Materials Science Changchun University of Technology  Changchun China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,27]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41563\u2010020\u201000886\u20100"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41587\u2010023\u201001679\u2010x"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41565\u2010020\u20100669\u20106"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.6b09643"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1039\/d0sc05447j"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202102451"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1039\/d5sc05796e"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202517229"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpj.2012.02.006"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.analchem.4c02270"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacsau.1c00128"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.4c09094"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.4c04212"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010025\u201059511\u2010w"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.nanolett.1c04677"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.4c12648"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010021\u201027325\u20101"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms25147518"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijbiomac.2023.125698"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jpcb.7b04824"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42003\u2010024\u201006472\u20103"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers12020436"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.3579"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/febs.70238"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1039\/d3tb02899b"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202209227"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mtbio.2025.102223"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010025\u201059501\u2010y"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010022\u201032064\u2010y"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010023\u201044317\u20105"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacsau.5c00432"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsami.5c20469"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202303973"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2017.495"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btu202"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.4c00360"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.0c02852"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcc.20945"}],"container-title":["Advanced Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.77389","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/advs.77389","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.77389","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T15:27:12Z","timestamp":1787844432000},"score":1,"resource":{"primary":{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/10.1002\/advs.77389"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,27]]},"references-count":38,"alternative-id":["10.1002\/advs.77389"],"URL":"https:\/\/doi.org\/10.1002\/advs.77389","archive":["Portico"],"relation":{},"ISSN":["2198-3844","2198-3844"],"issn-type":[{"value":"2198-3844","type":"print"},{"value":"2198-3844","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,27]]},"assertion":[{"value":"2026-06-18","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-17","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-27","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e77389"}}