{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T11:57:35Z","timestamp":1791460655232,"version":"4.3.4"},"reference-count":80,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T00:00:00Z","timestamp":1791417600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T00:00:00Z","timestamp":1791417600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100021856","name":"Ministero dell'Universit\u00e0 e della Ricerca","doi-asserted-by":"publisher","award":["Lancelot (PRIN 2022 PNRR; n\u00b0=P2022RBF5P)"],"award-info":[{"award-number":["Lancelot (PRIN 2022 PNRR; n\u00b0=P2022RBF5P)"]}],"id":[{"id":"10.13039\/501100021856","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100021856","name":"Ministero dell'Universit\u00e0 e della Ricerca","doi-asserted-by":"publisher","award":["OPTIMA (PRIN 2022; n\u00b0=2022598YAX)"],"award-info":[{"award-number":["OPTIMA (PRIN 2022; n\u00b0=2022598YAX)"]}],"id":[{"id":"10.13039\/501100021856","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["febs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["FEBS Open Bio"],"abstract":"<jats:p>Fluorination has become a key molecular engineering strategy in medicinal chemistry and nanomedicine, enabling the fine tuning of the physicochemical and biological properties of therapeutic molecules and drug delivery systems. The unique characteristics of fluorine, including its small steric footprint, high electronegativity, and exceptional strength of the C\u2013F bond, enhance metabolic stability, modulate lipophilicity and acidity, and improve pharmacokinetic profiles. Beyond these well\u2010established effects, fluorination has emerged as a tool for controlling the assembly and biological behavior of nanocarriers. Fluorinated biomolecules, polymers, dendrimers, and lipid\u2010based systems often display improved colloidal stability, reduced nonspecific protein adsorption, enhanced cellular uptake, and efficient endosomal escape, ultimately leading to superior intracellular delivery of nucleic acids, proteins, and other therapeutic cargoes. Here we summarize recent advances in the fluorination of both therapeutic cargoes and delivery carriers, emphasizing how different fluorination strategies, including single fluorine atoms, trifluoromethyl groups, linear perfluoroalkyl chains, and emerging short branched fluorinated motifs, can be exploited to optimize drug delivery performance. Attention is devoted to the relationship between fluorinated molecular architectures, self\u2010assembly, and bio\u2013nano interactions that govern biological activity. Furthermore, the advantages and limitations of current fluorination approaches are discussed. Finally, we highlight the need for a deeper mechanistic understanding of how fluorinated moieties interact with proteins and biological membranes. Advanced physicochemical techniques, including neutron and X\u2010ray scattering and reflectometry, are expected to provide fundamental insights into these processes, enabling the rational design of more effective, safer, and environmentally sustainable fluorinated therapeutics and nanomedicines.<\/jats:p>","DOI":"10.1002\/2211-5463.70354","type":"journal-article","created":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T11:29:24Z","timestamp":1791458964000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Fluorination: A strategy to tune the interactions of molecules and nanoscale systems with biological matter"],"prefix":"10.1002","author":[{"given":"Martina","family":"Beccalli","sequence":"first","affiliation":[{"name":"Laboratory of Supramolecular and Bio\u2010Nanomaterials, Department of Chemistry, Materials, and Chemical Engineering \u201cGiulio Natta\u201d Politecnico di Milano  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7363-8756","authenticated-orcid":false,"given":"Beatrice Lucia","family":"Bona","sequence":"additional","affiliation":[{"name":"Laboratory of Supramolecular and Bio\u2010Nanomaterials, Department of Chemistry, Materials, and Chemical Engineering \u201cGiulio Natta\u201d Politecnico di Milano  Milan Italy"},{"name":"Department of Medical Biotechnology and Translational Medicine University of Milan  Segrate Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8138-9246","authenticated-orcid":false,"given":"Francesca","family":"Baldelli Bombelli","sequence":"additional","affiliation":[{"name":"Laboratory of Supramolecular and Bio\u2010Nanomaterials, Department of Chemistry, Materials, and Chemical Engineering \u201cGiulio Natta\u201d Politecnico di Milano  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,8]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1039\/b610213c"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1021\/cr4002879"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.3390\/ph16081162"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1039\/C1CS15084G"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.accounts.1c00766"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.3c04507"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.colsurfb.2023.113730"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms4053"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1039\/C8OB00991K"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/adhm.201700978"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.nanolett.8b02553"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1039\/D3TB00516J"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2519823123"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.1c05250"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.carbpol.2018.12.063"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.accounts.1c00125"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.aaz1774"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/ange.202419996"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1039\/D5NR03209A"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010018\u201003779\u20108"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1074\u20105521(00)00139\u20103"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc1074"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1080\/14756360701425014"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022\u20101139(01)00375\u2010X"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.5b00258"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1039\/D5OB00997A"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2023.115476"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.3762\/bjoc.6.38"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41573\u2010020\u20100075\u20107"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41565\u2010021\u201000898\u20100"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1039\/C3SC52932K"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201006519"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja075373f"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.5c00922"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1039\/D2NR01648F"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/cbic.202400436"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gky037"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.analchem.8b01005"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.3390\/ph15101201"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.bioconjchem.3c00245"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.biomac.4c00872"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1002\/chem.202002078"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.chemmater.8b02115"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10334\u2010018\u20100724\u20106"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eurpolymj.2022.111381"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1039\/D5TB01933H"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202404645"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41565\u2010020\u201000781\u20104"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1039\/C7TB02158E"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsmedchemlett.6b00453"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1021\/bc900469z"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejps.2021.106004"},{"key":"e_1_2_8_54_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12032\u2010025\u201003022\u20107"},{"key":"e_1_2_8_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2014.03.040"},{"key":"e_1_2_8_56_1","doi-asserted-by":"publisher","DOI":"10.1021\/acssuschemeng.8b00777"},{"key":"e_1_2_8_57_1","doi-asserted-by":"publisher","DOI":"10.1039\/C7GC03081A"},{"key":"e_1_2_8_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.reactfunctpolym.2026.106709"},{"key":"e_1_2_8_59_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.orglett.8b02976"},{"key":"e_1_2_8_60_1","doi-asserted-by":"publisher","DOI":"10.1039\/D1CC02133H"},{"key":"e_1_2_8_61_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.chemrev.3c00705"},{"key":"e_1_2_8_62_1","doi-asserted-by":"publisher","DOI":"10.3390\/polym10020161"},{"key":"e_1_2_8_63_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsanm.5c05222"},{"key":"e_1_2_8_64_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsami.4c00910"},{"key":"e_1_2_8_65_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpharm.2026.127219"},{"key":"e_1_2_8_66_1","doi-asserted-by":"publisher","DOI":"10.1039\/D0NR08200G"},{"key":"e_1_2_8_67_1","doi-asserted-by":"crossref","unstructured":"LeterrierC M\u00e9riauxS GravelEandDorisE(2025)Light\u2010triggered quenching of the 19F\u2010MRI signal from micelle\u2010encapsulated PERFECTA.10.26434\/chemrxiv\u20102025\u2010g6lr3","DOI":"10.26434\/chemrxiv-2025-g6lr3"},{"key":"e_1_2_8_68_1","doi-asserted-by":"publisher","DOI":"10.1039\/C4PY00882K"},{"key":"e_1_2_8_69_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2005.09.017"},{"key":"e_1_2_8_70_1","doi-asserted-by":"publisher","DOI":"10.1039\/C4TB00171K"},{"key":"e_1_2_8_71_1","doi-asserted-by":"publisher","DOI":"10.1002\/mabi.202100024"},{"key":"e_1_2_8_72_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2016.09.023"},{"key":"e_1_2_8_73_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.macromol.2c00129"},{"key":"e_1_2_8_74_1","doi-asserted-by":"publisher","DOI":"10.1002\/ejoc.201700566"},{"key":"e_1_2_8_75_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacsau.5c00198"},{"key":"e_1_2_8_76_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsmaterialsau.3c00032"},{"key":"e_1_2_8_77_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41578\u2010021\u201000358\u20100"},{"key":"e_1_2_8_78_1","doi-asserted-by":"publisher","DOI":"10.1002\/jgm.166"},{"key":"e_1_2_8_79_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0068305"},{"key":"e_1_2_8_80_1","doi-asserted-by":"publisher","DOI":"10.1021\/la200450x"},{"key":"e_1_2_8_81_1","doi-asserted-by":"publisher","DOI":"10.3390\/ph16111583"}],"container-title":["FEBS Open Bio"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/febs.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/2211-5463.70354","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/febs.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/2211-5463.70354","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/febs.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/2211-5463.70354","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T11:29:26Z","timestamp":1791458966000},"score":1,"resource":{"primary":{"URL":"https:\/\/febs.onlinelibrary.wiley.com\/doi\/10.1002\/2211-5463.70354"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,8]]},"references-count":80,"alternative-id":["10.1002\/2211-5463.70354"],"URL":"https:\/\/doi.org\/10.1002\/2211-5463.70354","archive":["Portico"],"relation":{},"ISSN":["2211-5463","2211-5463"],"issn-type":[{"value":"2211-5463","type":"print"},{"value":"2211-5463","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,8]]},"assertion":[{"value":"2026-06-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-29","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-08","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"2211-5463.70354"}}