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However, the known methods for drug transport across the BBB are generally complicated and inefficient, and exhibit serious side effects in some cases. Herein, we report an exciting finding that fluorination and betaine modification can significantly augment the BBB\u2010crossing ability of cylindrical polymer brushes (CPBs), which was demonstrated by the comparison with the CPBs modified with alkyl and poly(ethylene glycol) chains, respectively. We surmise that fluorination enhances the BBB penetration of the CPBs by increasing the hydrophobicity and reducing the surface energy, and betaine medication achieves this function via a betaine transporter BGT1 expressed on brain capillaries. By means of an in vitro BBB model, we demonstrated that the CPBs penetrated the BBB through transendothelial transport. This work provides a novel strategy for enhancing the BBB\u2010crossing ability of nanomaterials.<\/jats:p>","DOI":"10.1002\/anie.202201390","type":"journal-article","created":{"date-parts":[[2022,2,10]],"date-time":"2022-02-10T11:04:38Z","timestamp":1644491078000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Fluorination and Betaine Modification Augment the Blood\u2013Brain Barrier\u2010Crossing Ability of Cylindrical Polymer Brushes"],"prefix":"10.1002","volume":"61","author":[{"given":"Ruonan","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Polymer Science &amp; Engineering College of Chemistry &amp; Chemical Engineering Nanjing University  Nanjing 210023 P. R. 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