Amphipathic β-cyclodextrin nanocarriers serve as intelligent delivery platform for anticancer drug

A novel glutathione-responsive (GSH-responsive) star-like amphiphilic polymer (C₁₂H₂₅)₁₄-β-CD-(S-S-mPEG)₇ (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.