{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T20:17:55Z","timestamp":1785874675994,"version":"3.56.0"},"reference-count":71,"publisher":"Wiley","issue":"43","license":[{"start":{"date-parts":[[2023,9,14]],"date-time":"2023-09-14T00:00:00Z","timestamp":1694649600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000078","name":"Division of Materials Research","doi-asserted-by":"publisher","award":["1506937"],"award-info":[{"award-number":["1506937"]}],"id":[{"id":"10.13039\/100000078","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000078","name":"Division of Materials Research","doi-asserted-by":"publisher","award":["2119653"],"award-info":[{"award-number":["2119653"]}],"id":[{"id":"10.13039\/100000078","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Angew Chem Int Ed"],"published-print":{"date-parts":[[2023,10,23]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Nonionic hydrogels are of particular interest for long\u2010term therapeutic implantation due to their minimal immunogenicity relative to their charged counterparts. However, in situ formation of nonionic supramolecular hydrogels under physiological conditions has been a challenging task. In this context, we report on our discovery of salt\u2010triggered hydrogelation of nonionic supramolecular polymers (SPs) formed by self\u2010assembling prodrug hydrogelators (SAPHs) through the Hofmeister effect. The designed SAPHs consist of two SN\u201038 units, which is an active metabolite of the anticancer drug irinotecan, and a short peptide grafted with two or four oligoethylene glycol (OEG) segments. Upon self\u2010assembly in water, the resultant nonionic SPs can be triggered to gel upon addition of phosphate salts. Our <jats:sup>1<\/jats:sup>H NMR studies revealed that the added phosphates led to a change in the chemical shift of the methylene protons, suggestive of a disruption of the water\u2010ether hydrogen bonds and consequent reorganization of the hydration shell surrounding the SPs. This deshielding effect, commensurate with the amount of salt added, likely promoted associative interactions among the SAPH filaments to percolate into a 3D network. The formed hydrogels exhibited a sustained release profile of SN\u201038 hydrogelator that acted potently against cancer cells.<\/jats:p>","DOI":"10.1002\/anie.202306652","type":"journal-article","created":{"date-parts":[[2023,9,5]],"date-time":"2023-09-05T11:27:08Z","timestamp":1693913228000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Utilizing the Hofmeister Effect to Induce Hydrogelation of Nonionic Supramolecular Polymers into a Therapeutic Depot"],"prefix":"10.1002","volume":"62","author":[{"given":"Han","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Chemical and Biomolecular Engineering and Institute for NanoBioTechnology The Johns Hopkins University  Baltimore MD 21218 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Su","sequence":"additional","affiliation":[{"name":"Department of Chemical and Biomolecular Engineering and Institute for NanoBioTechnology The Johns Hopkins University  Baltimore MD 21218 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tian","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Chemical and Biomolecular Engineering and Institute for NanoBioTechnology The Johns Hopkins University  Baltimore MD 21218 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4684-2655","authenticated-orcid":false,"given":"Honggang","family":"Cui","sequence":"additional","affiliation":[{"name":"Department of Chemical and Biomolecular Engineering and Institute for NanoBioTechnology The Johns Hopkins University  Baltimore MD 21218 USA"},{"name":"Department of Materials Science and Engineering The Johns Hopkins University  Baltimore MD 21218 USA"},{"name":"Department of Oncology and Sidney Kimmel Comprehensive Cancer Center Johns Hopkins University School of Medicine  Baltimore MD 21205 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,9,14]]},"reference":[{"key":"e_1_2_7_1_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1205962"},{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1021\/cr500633b"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1021\/cr900181u"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1039\/b607706d"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1039\/C4CC06340F"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.chemrev.5b00299"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.7b08190"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja027993g"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.1c07925"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2005.04.002"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.nanolett.2c00967"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmat4474"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0600559103"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1021\/bc050153h"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1039\/C7CS00793K"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.7b04655"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja404215g"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2012.06.003"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2019.08.003"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.1c04570"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1039\/C1CC15551B"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja3115983"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.9b09848"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2022.03.003"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2022.06.037"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2204621120"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1039\/D2BM01649D"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2021.121182"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.3c01748"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41565-021-00961-w"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.5b13541"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1039\/C7CS00391A"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2012.08.060"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/adfm.201807446"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmat2442"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.3330"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd1033"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmat2778"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1002\/adfm.200500161"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1009592107"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1021\/nn2025397"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.chemrev.7b00305"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.5b06011"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.1c01241"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1039\/C3CC49453E"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0805374105"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1224741"},{"key":"e_1_2_7_48_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1521-4095(199811)10:16<1343::AID-ADMA1343>3.0.CO;2-Z"},{"key":"e_1_2_7_49_1","doi-asserted-by":"publisher","DOI":"10.1021\/cr60158a004"},{"key":"e_1_2_7_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chemosphere.2006.03.029"},{"key":"e_1_2_7_51_1","doi-asserted-by":"publisher","DOI":"10.1021\/jp807993f"},{"key":"e_1_2_7_52_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja0546424"},{"key":"e_1_2_7_53_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja412952y"},{"key":"e_1_2_7_54_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jpcb.6b08923"},{"key":"e_1_2_7_55_1","doi-asserted-by":"publisher","DOI":"10.1039\/C6CP08214A"},{"key":"e_1_2_7_56_1","doi-asserted-by":"publisher","DOI":"10.1038\/nchem.1899"},{"key":"e_1_2_7_57_1","doi-asserted-by":"publisher","DOI":"10.1021\/cr200271j"},{"key":"e_1_2_7_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbpa.2006.09.020"},{"key":"e_1_2_7_59_1","doi-asserted-by":"publisher","DOI":"10.1039\/C4CP04564E"},{"key":"e_1_2_7_60_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1152799"},{"key":"e_1_2_7_61_1","doi-asserted-by":"publisher","DOI":"10.1039\/b807129b"},{"key":"e_1_2_7_62_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja047715c"},{"key":"e_1_2_7_63_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41557-021-00805-z"},{"key":"e_1_2_7_64_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja301297g"},{"key":"e_1_2_7_65_1","doi-asserted-by":"crossref","unstructured":"C.\u2005Q. Sun inSolvation Dynamics: A Notion of Charge Injection(Ed.: C.\u2005Q. Sun) Springer Singapore 2019 pp. 129\u2013189.","DOI":"10.1007\/978-981-13-8441-7_6"},{"key":"e_1_2_7_66_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1183512"},{"key":"e_1_2_7_67_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jpcb.9b05532"},{"key":"e_1_2_7_68_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2010.09.044"},{"key":"e_1_2_7_69_1","doi-asserted-by":"publisher","DOI":"10.1021\/jp8062977"},{"key":"e_1_2_7_70_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.physchem.59.032607.093635"},{"key":"e_1_2_7_71_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.9b01689"}],"container-title":["Angewandte Chemie International Edition"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/am-pdf\/10.1002\/anie.202306652","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/anie.202306652","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,7,24]],"date-time":"2025-07-24T15:18:38Z","timestamp":1753370318000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/anie.202306652"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,9,14]]},"references-count":71,"journal-issue":{"issue":"43","published-print":{"date-parts":[[2023,10,23]]}},"alternative-id":["10.1002\/anie.202306652"],"URL":"https:\/\/doi.org\/10.1002\/anie.202306652","archive":["Portico"],"relation":{},"ISSN":["1433-7851","1521-3773"],"issn-type":[{"value":"1433-7851","type":"print"},{"value":"1521-3773","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,9,14]]},"assertion":[{"value":"2023-05-12","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-09-14","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e202306652"}}