Wang Ruonan, Yang Shuo, Xiao Panpan, Sun Ying, Li Jia, Jiang Xiqun, Wu Wei
Department of Polymer Science & Engineering, College of Chemistry & Chemical Engineering, Nanjing University, Nanjing, 210023, P. R. China.
Angew Chem Int Ed Engl. 2022 May 2;61(19):e202201390. doi: 10.1002/anie.202201390. Epub 2022 Feb 24.
Blood-brain barrier (BBB)-crossing ability of drugs is of paramount importance for the treatments of central nervous system diseases. 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-crossing 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-crossing ability of nanomaterials.
药物穿越血脑屏障（BBB）的能力对于中枢神经系统疾病的治疗至关重要。然而，已知的药物跨血脑屏障转运方法通常复杂且低效，并且在某些情况下会表现出严重的副作用。在此，我们报告了一个令人兴奋的发现，即氟化和甜菜碱修饰可以显著增强圆柱形聚合物刷（CPB）穿越血脑屏障的能力，这通过分别与用烷基链和聚乙二醇链修饰的CPB进行比较得到了证明。我们推测，氟化通过增加疏水性和降低表面能来增强CPB对血脑屏障的穿透能力，而甜菜碱修饰则通过脑毛细血管上表达的甜菜碱转运体BGT1实现这一功能。通过体外血脑屏障模型，我们证明CPB通过跨内皮转运穿透血脑屏障。这项工作为增强纳米材料穿越血脑屏障的能力提供了一种新策略。
