College of Chemistry and Chemical Engineering, Central South University, Changsha, Hunan, 410083, PR China.
College of Chemistry and Chemical Engineering, Central South University, Changsha, Hunan, 410083, PR China.
Colloids Surf B Biointerfaces. 2019 Aug 1;180:429-440. doi: 10.1016/j.colsurfb.2019.05.011. Epub 2019 May 8.
A novel glutathione-responsive (GSH-responsive) star-like amphiphilic polymer (CH)-β-CD-(S-S-mPEG) (denoted as CCSP) was designed for efficient antitumor drug delivery. The amphiphilic β-cyclodextrin (β-CD) self-polymerize in water to form a sphere with a diameter of 40-50 nm. The secondary hydroxyl groups of β-CD were modified by dodecyl to form a hydrophobic core and the primary hydroxyl groups of β-CD were decorated with PEG through disulfide bond to form a hydrophilic shell. Since the hydrophobic cavity of β-CD was maintained, the hydrophobic core formed by dodecyl as well as cavity of β-CD provided CCSP with a loading content as high as 39.6 wt%. Importantly, DOX@CCSP exhibited low drug leakage and negligible cytotoxicity in non-reductive physiological environment, while it showed rapid release and high cytotoxicity in reductive tumorous environment via the breakage of disulfide bond. In view of the above-mentioned advantages of DOX@CCSP nanocarriers such as high loading content, proper size, favorable stimulus-response release performance and low leakage, it is believed that CCSP may offer great potential to be used as an intelligent nanocarrier for anticancer drug delivery.
一种新型的谷胱甘肽响应(GSH 响应)星型两亲聚合物(CH)-β-CD-(S-S-mPEG)(表示为 CCSP)被设计用于高效的抗肿瘤药物传递。两亲性β-环糊精(β-CD)在水中自组装形成直径为 40-50nm 的球体。β-CD 的二级羟基被十二烷基化形成疏水核,β-CD 的一级羟基通过二硫键修饰聚乙二醇形成亲水壳。由于β-CD 的疏水腔得以保留,十二烷基形成的疏水核以及β-CD 的腔为 CCSP 提供了高达 39.6wt%的载药含量。重要的是,DOX@CCSP 在非还原生理环境中表现出低药物泄漏和可忽略的细胞毒性,而在还原肿瘤环境中通过二硫键的断裂则表现出快速释放和高细胞毒性。鉴于 DOX@CCSP 纳米载体的上述优点,如高载药含量、适当的尺寸、有利的刺激响应释放性能和低泄漏,相信 CCSP 可能具有很大的潜力被用作智能纳米载体用于抗癌药物传递。