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However, how the mechanical properties of nanoformulations affect their ultimate brain destination is still unknown. Here, a library of membrane\u2010crosslinked polymersomes with different elasticity are synthesized to investigate their ability to effectively target brain tumors. Crosslinked polymersomes with identical particle size, zeta potential and shape are assessed, but their elasticity is varied depending on the rigidity of incorporated crosslinkers. Benzyl and oxyethylene containing crosslinkers demonstrate higher and lower Young's modulus, respectively. Interestingly, stiff polymersomes exert superior brain tumor cell uptake, excellent in vitro blood brain barrier (BBB) and tumor penetration but relatively shorter blood circulation time than their soft counterparts. These results together affect the in vivo performance for which rigid polymersomes exerting higher brain tumor accumulation in an orthotopic glioblastoma (GBM) tumor model. The results demonstrate the crucial role of nanoformulation elasticity for brain\u2010tumor targeting and will be useful for the design of future brain targeting drug delivery systems for the treatment of brain disease.<\/jats:p>","DOI":"10.1002\/advs.202102001","type":"journal-article","created":{"date-parts":[[2021,8,23]],"date-time":"2021-08-23T01:54:04Z","timestamp":1629683644000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":42,"title":["Tuning the Elasticity of Polymersomes for Brain Tumor Targeting"],"prefix":"10.1002","volume":"8","author":[{"given":"Meng","family":"Zheng","sequence":"first","affiliation":[{"name":"Henan and Macquarie University Joint Centre for Biomedical Innovation School of Life Sciences Henan University  Kaifeng 475004 China"},{"name":"Henan Key Laboratory of Brain Targeted Bio\u2010nanomedicine School of Life Sciences &amp; School of Pharmacy Henan University  Kaifeng 475004 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiuli","family":"Du","sequence":"additional","affiliation":[{"name":"Henan and Macquarie University Joint Centre for Biomedical Innovation School of Life Sciences Henan University  Kaifeng 475004 China"},{"name":"Henan Key Laboratory of Brain Targeted Bio\u2010nanomedicine School of Life Sciences &amp; 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