In this study, a novel cyclodextrin derivative, i.e., zwitterionic choline phosphate (CP)‐functionalized β‐cyclodextrin (CP‐β‐CD) is successfully synthesized by click chemistry reaction. CP‐β‐CD has excellent cell‐membrane‐targeted ability because of the CP group can bind to phosphate choline (PC) in the cell membrane and promote the cellular uptake. Due to the introduction of CP group on β‐CD, it disrupts the hydrogen network between natural β‐CD molecules. Meanwhile, the water solubility of CP‐β‐CD is improved dramatically to 816 mg mL⁻¹, which is 440 times as that of unmodified β‐CD. Apatinib, a small molecular inhibitor, is used as a model of hydrophobic drug and loaded into CP‐β‐CD to study the solubilization effect and the anti‐angiogenisis activity. In addition, the cytotoxicity of CP‐β‐CD is also studied, and it is demonstrated that CP‐β‐CD is nontoxic. These results indicate that the apatinib can be transported into cell interior and play an excellent anti‐angiogenisis activity after being loaded into CP‐β‐CD drug delivery system. This work suggests that the water soluble CP‐β‐CD with excellent cell internalization efficiency has a potential application prospect in the field of drug delivery.

中文翻译：

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基于胆碱-磷酸酯功能化β-环糊精的细胞膜靶向给药系统。

本研究通过点击化学反应成功合成了一种新型环糊精衍生物，即两性离子磷酸胆碱（CP）功能化的β-环糊精（CP-β-CD）。CP-β-CD 具有优异的细胞膜靶向能力，因为 CP 基团可以与细胞膜中的磷酸胆碱 (PC) 结合并促进细胞摄取。由于在 β-CD 上引入了 CP 基团，它破坏了天然 β-CD 分子之间的氢网络。同时，CP-β-CD 的水溶性显着提高至 816 mg mL ^-1，是未修饰的 β-CD 的 440 倍。阿帕替尼是一种小分子抑制剂，被用作疏水性药物的模型并加载到CP-β-CD中以研究增溶作用和抗血管生成活性。此外，还研究了 CP-β-CD 的细胞毒性，证明 CP-β-CD 是无毒的。这些结果表明，阿帕替尼加载到CP-β-CD给药系统后可以被转运到细胞内部并发挥优异的抗血管生成活性。这项工作表明具有优异细胞内化效率的水溶性CP-β-CD在药物递送领域具有潜在的应用前景。